U.S. GOVERNMENT PRINTING OFFICE

55–639CC WASHINGTON : 1999

WOMEN’S HEALTH: RAISING AWARENESS OF

CERVICAL CANCER

HEARING

BEFORE THE

SUBCOMMITTEE ON

HEALTH AND ENVIRONMENT

OF THE

COMMITTEE ON COMMERCE

HOUSE OF REPRESENTATIVES

ONE HUNDRED SIXTH CONGRESS

FIRST SESSION

MARCH 16, 1999

Serial No. 106–4

Printed for the use of the Committee on Commerce

(
COMMITTEE ON COMMERCE

TOM BLILEY, Virginia, Chairman

W.J. ‘‘BILLY’’ TAUZIN, Louisiana

MICHAEL G. OXLEY, Ohio

MICHAEL BILIRAKIS, Florida

JOE BARTON, Texas

FRED UPTON, Michigan

CLIFF STEARNS, Florida

PAUL E. GILLMOR, Ohio

Vice Chairman

JAMES C. GREENWOOD, Pennsylvania

CHRISTOPHER COX, California

NATHAN DEAL, Georgia

STEVE LARGENT, Oklahoma

RICHARD BURR, North Carolina

BRIAN P. BILBRAY, California

ED WHITFIELD, Kentucky

GREG GANSKE, Iowa

CHARLIE NORWOOD, Georgia

TOM A. COBURN, Oklahoma

RICK LAZIO, New York

BARBARA CUBIN, Wyoming

JAMES E. ROGAN, California

JOHN SHIMKUS, Illinois

HEATHER WILSON, New Mexico

JOHN B. SHADEGG, Arizona

CHARLES W. ‘‘CHIP’’ PICKERING,

Mississippi

VITO FOSSELLA, New York

ROY BLUNT, Missouri

ED BRYANT, Tennessee

ROBERT L. EHRLICH, Jr., Maryland

JOHN D. DINGELL, Michigan

HENRY A. WAXMAN, California

EDWARD J. MARKEY, Massachusetts

RALPH M. HALL, Texas

RICK BOUCHER, Virginia

EDOLPHUS TOWNS, New York

FRANK PALLONE, Jr., New Jersey

SHERROD BROWN, Ohio

BART GORDON, Tennessee

PETER DEUTSCH, Florida

BOBBY L. RUSH, Illinois

ANNA G. ESHOO, California

RON KLINK, Pennsylvania

BART STUPAK, Michigan

ELIOT L. ENGEL, New York

THOMAS C. SAWYER, Ohio

ALBERT R. WYNN, Maryland

GENE GREEN, Texas

KAREN MCCARTHY, Missouri

TED STRICKLAND, Ohio

DIANA DEGETTE, Colorado

THOMAS M. BARRETT, Wisconsin

BILL LUTHER, Minnesota

LOIS CAPPS, California

JAMES E. DERDERIAN, Chief of Staff

JAMES D. BARNETTE, General Counsel

REID P.F. STUNTZ, Minority Staff Director and Chief Counsel

SUBCOMMITTEE ON HEALTH AND ENVIRONMENT

MICHAEL BILIRAKIS, Florida, Chairman

FRED UPTON, Michigan

CLIFF STEARNS, Florida

JAMES C. GREENWOOD, Pennsylvania

NATHAN DEAL, Georgia

RICHARD BURR, North Carolina

BRIAN P. BILBRAY, California

ED WHITFIELD, Kentucky

GREG GANSKE, Iowa

CHARLIE NORWOOD, Georgia

TOM A. COBURN, Oklahoma

Vice Chairman

RICK LAZIO, New York

BARBARA CUBIN, Wyoming

JOHN B. SHADEGG, Arizona

CHARLES W. ‘‘CHIP’’ PICKERING,

Mississippi

ED BRYANT, Tennessee

TOM BLILEY, Virginia,

(Ex Officio)

SHERROD BROWN, Ohio

HENRY A. WAXMAN, California

FRANK PALLONE, Jr., New Jersey

PETER DEUTSCH, Florida

BART STUPAK, Michigan

GENE GREEN, Texas

TED STRICKLAND, Ohio

DIANA DEGETTE, Colorado

THOMAS M. BARRETT, Wisconsin

LOIS CAPPS, California

RALPH M. HALL, Texas

EDOLPHUS TOWNS, New York

ANNA G. ESHOO, California

JOHN D. DINGELL, Michigan,

(Ex Officio)

(II)
2

C O N T E N T S

Page

Testimony of:

Cox, John Thomas, Student Health Services, University of California

at Santa Barbara .......................................................................................... 82

Eshoo, Hon. Anna G., a Representative in Congress from the State of

California ....................................................................................................... 6

Gatscha, Rosemarie, Cytology Manager, American Society of Clinical Pathologists ........................................................................................................ 91

Lee, Nancy C., Associate Director for Science, Center for Disease Control

and Prevention .............................................................................................. 22

Lenhart, Sharyn, Immediate Past President, American Medical Women’s

Association ..................................................................................................... 88

Lowey, Douglas R., Deputy Director, National Cancer Institute ................. 27

Mack, Hon. Connie, a United States Senator from the State of Florida ..... 8

Piker, Linda Grace, Cervical Cancer Survivor ............................................... 73

Trimble, Edward L., Head Surgery Section, National Cancer Institute ...... 26

Valdiserri, Ronald O., Deputy Director, Center for Disease Control and

Prevention ..................................................................................................... 16

Material submitted for the record by:

Center for Cervical Health, prepared statement of ....................................... 101

Center for Disease Control, responses to questions for the record ............... 132

Lowey, Douglas R., Deputy Director, National Cancer Institute, letter

dated April 8, 1999, enclosing response for the record .............................. 105

Trimble, Edward L., Head Surgery Section, National Cancer Institute,

letter dated April 8, 1999, enclosing response for the record .................... 103

(III)
(1)

WOMEN’S HEALTH: RAISING AWARENESS OF

CERVICAL CANCER

TUESDAY, MARCH 16, 1999

HOUSE OF REPRESENTATIVES, COMMITTEE ON COMMERCE, SUBCOMMITTEE ON HEALTH AND ENVIRONMENT, Washington, DC.

The subcommittee met, pursuant to notice, at 2:57 p.m., in room

2123, Rayburn House Office Building, Hon. Michael Bilirakis

(chairman) presiding.

Members present: Representatives Bilirakis, Stearns, Greenwood, Bilbray, Ganske, Coburn, Lazio, Bryant, Brown, Green, Barrett, Capps, Towns, and Eshoo.

Staff present: Lori Wall, majority counsel; Marc Wheat, majority

counsel; Mike Flood, legislative clerk; John Ford, minority counsel,

and Kristi Guillory, minority legislative fellow.

Mr. BILIRAKIS. The hearing will come to order.

Today the subcommittee will hold the first in a series of hearings

on women’s health concerns by focusing on the issue of cervical

cancer, its causes, and its treatments. Each year approximately

15,000 women are diagnosed with cervical cancer in the United

States, and almost 5,000 die annually from the disease. Troubling

evidence also shows a higher incidence of cervical cancer among

minority and disadvantaged populations. The tragedy of these statistics is compounded by the fact that cervical cancer is readily

treatable if caught at an early stage.

Last year I sponsored legislation which was enacted into law to

reauthorize the National Breast and Cervical Cancer Early Detection Program at the Centers for Disease Control and Prevention.

This women’s health initiative had strong bipartisan support, including the subcommittee’s ranking member, Mr. Brown, the full

committee chairman, Tom Bliley, and the full committee ranking

member John Dingell.

Today we will learn about recent progress in the fight against

this terrible disease. We know that the primary risk factor and

leading cause of cervical cancer is the human papillomavirus or

HPV, a sexually transmitted disease. Experts estimate that 24 million Americans are infected with HPV, and the incidence of this

virus may be increasing.

The good news is that the human immune system can normally

clear the virus within 18 months. As a result, many women do not

realize they have contracted HPV and they never suffer any health

consequences from it. Unfortunately, that is not always the case.

It is critical that all women understand the threat of cervical can-
2

cer and the importance of regular Pap smear exams. We must increase awareness of how it is transmitted and the importance of

early detection. We must also improve methods of detecting the

presence of pre-cancerous lesions that develop into cervical cancer.

Later this year I will be participating in a women’s health fair

in my congressional district. I encourage my colleagues to help educate the public about this disease and other women’s health concerns. In that regard, I want to commend the efforts of Senator

Connie Mack of my home State of Florida, and Representatives

Juanita Millender-McDonald, Rick Lazio, and Tom Coburn in sponsoring a resolution to raise awareness of cervical cancer.

Let me also thank our witnesses for taking the time to join us

today, and again extend a special welcome to my Florida colleague,

Senator Connie Mack. Connie, do you have the time to wait for the

opening statements before testifying?

Senator MACK. Sure.

Mr. BILIRAKIS. Okay. I first want to applaud the work that you

and Priscilla have done in the fight against cancer. You certainly

will be missed in the Senate, but I trust your leadership in these

issues will continue.

I now recognize the ranking member, Mr. Brown of Ohio.

Mr. BROWN. Thank you, Mr. Chairman, for arranging this hearing. I would also like to thank Senator Mack and Congresswoman

Eshoo for their fine work, and our other distinguished panelists

today. While I am pleased that the subcommittee will hear from a

wide range of witnesses, I am disappointed that it was not possible

to include a representative from the College of American Pathologists. This organization, representing some 16,000 physicians, offers a unique perspective on the detection, diagnosis, and treatment of cervical cancer. Their input would have been extremely

valuable.

The tragedy of cervical cancer is twofold. It is tragic that hundreds of thousands of women confront this disease, a profoundly debilitating and deadly illness. It is tragic that cervical cancer remains such a virulent killer, when it is within our power to prevent

it. Cervical cancer is a national and international public health

issue. It accounts for 6 percent of cancers diagnosed in women in

the United States, taking nearly 5,000 lives. Worldwide, more than

470,000 new cases are diagnosed each year.

In both industrialized and non-industrialized nations, cervical

cancer takes its greatest toll on those individuals least able to fight

back, minority populations and the economic disadvantaged. Cervical cancer deaths can be virtually eliminated through behavioral

changes, early detection, and timely access to treatment, all of

which hinge on public awareness. Public awareness fuels change.

It can generate the individual and collective actions necessary to

achieve a meaningful reduction in cervical cancer rates.

The public needs to know that safe behaviors and proper screening can reduce cervical cancer death rates dramatically. We need

to get them the facts about screening test accuracy, new detection

methods, and treatment breakthroughs, so they can play an active

role in prevention and treatment decisions. We need to emphasize

the potential inherent in a national commitment to combat this disease.
3

The public needs to know about initiatives like the CDC’s Breast

and Cervical Cancer Early Detection Program, which has reached

millions of uninsured women with free screening tests. Public

awareness can help us gather the resources needed for CDC and

its State and local partners to do more than scratch the surface of

this problem. As currently funded, the CDC program reaches only

15 percent of uninsured women. We can do much better than that.

We need to spread the word about initiatives like H.R. 1070, legislation introduced by Ms. Eshoo, which would ensure proper treatment for women who are screened under the CDC program and diagnosed with cancer. Diagnosis is a cruel and fiscally irresponsible

exercise when women diagnosed with cancer have no access to

treatment, as happens all too often in this society.

Finally, we must all become more sensitive to potential barriers

blocking proper cervical cancer screening. Pap smears have dramatically reduced cervical cancer deaths, and it is critical that we

do everything in our power to ensure their continued availability.

In that context, we must be vigilant in evaluating the adequacy

of Federal reimbursement for Pap smears. Medicare and Medicaid

reimbursement directly affects access for two populations particularly vulnerable to cervical cancer: low-income individuals and the

elderly. Since private reimbursement is often based on Federal payment rates, our actions indirectly affect millions of women with employer-sponsored or individual insurance coverage. It is imperative

that Federal reimbursement accurately reflect the true costs of performing and evaluating Pap smears.

Inadequate data on cervical cancer incidence rates is one of our

greatest obstacles, a problem to which too little attention is paid.

Our current data lumps different subpopulations together, potentially masking wide variations in cervical cancer rates. It is critical

to understand these differences in order to target prevention and

treatment initiatives appropriately. Knowledge fuels advocacy, and

in the case of cervical cancer, advocacy will save countless lives.

That is why today’s hearing on cervical cancer awareness is so valuable.

Mr. BILIRAKIS. I thank the gentleman. The Chair recognizes the

gentleman from Oklahoma, Dr. Coburn.

Mr. COBURN. Thank you Mr. Chairman. I, too, want to congratulate you on having this hearing. This is a subject matter which, unfortunately, I know way too much about. Last year I treated over

200 women with carcinoma in situ of the cervix. Seven of those had

invasive carcinoma. But there were thousands that went through

our clinic that had cervical dysplasia.

Not only is the knowledge not out there, the government entities,

in terms of this disease, have done a miserable job, in my estimation, of raising public awareness of this. We are not just talking

about cervical cancer. There are studies now that show that the

human papillomavirus can be transmitted from the mother in utero

to her child; that, in fact, you can culture newborn children about

40 percent of the time with this virus. It is theoretically possible

that a young woman never exposed could die of carcinoma of the

cervix because she contracted that virus in utero or at birth.

There are many studies that are ongoing now to look at these

issues. My fear and my worry is not that we will make awareness
4

of these issues possible, but that we will somehow average and

marginalize the best public health policy for preventing this disease.

I look forward to the testimony that we have and I yield back

my time.

Mr. BILIRAKIS. I thank the gentleman. The gentlelady from California, Ms. Capps.

Mrs. CAPPS. Thank you Mr. Chairman. I appreciate that you are

holding this hearing today on such an important topic, raising

awareness of cervical cancer, and I want to welcome all of the witnesses.

Senator Mack, I know that you are representing Priscilla as well.

My colleague, Anna Eshoo, a leader in this area, I look forward

to hearing from you.

I want to particularly welcome one of our expert panelists today,

Dr. J. Thomas Cox, who is a constituent of mine from the University of California at Santa Barbara. An accomplished OB-GYN, Dr.

Cox oversees student health services at UCSB, where he runs a

program that screens thousands of women for cervical cancer each

year. He is an expert in the area of cervical cancer treating, and

will today share his broad knowledge on the problems associated

with present cervical cancer screening and opportunities to improve

this system. I am so proud that Dr. Cox is here to represent the

medical expertise worldwide and at UCSB in the 22nd district of

California.

As a nurse, I have seen firsthand how important it is to raise

awareness of cervical cancer, especially since it is so highly treatable if caught early. The vast majority of cases of cervical cancer

are caused by the human papillomavirus, otherwise known as

HPV, a sexually transmitted agent that infects the cells of the cervix and slowly causes cellular changes that can result in cancer.

Women are often infected with HPV in their teens, 20’s or 30’s,

though the disease can take up to 20 years after the HPV infection

starts before the development of the disease begins. It starts with

an in situ stage that can be treated, but then as it progresses to

an invasive disease, it can often be fatal.

Cervical cancer prevention efforts worldwide have focused on

screening women at risk of the disease through Pap smears and

treating pre-cancerous lesions. Where screening quality and coverage have been high, these efforts have reduced invasive cervical

cancer by as much as 90 percent, and that is a remarkable number.

Since pre-cancerous and very early cervical cancers are nearly 100

percent curable, this test can prevent nearly all deaths from cervical cancer.

In reading the remarks that Dr. Cox has prepared for today’s

presentation, I learned that the decrease in the rate of cervical cancer in the United States is so dramatic that Pap smear screening

is one of the few interventions to receive an ‘‘A’’ recommendation

from the U.S. Preventive Services Task Force, and that is quite an

endorsement. Pap smears have changed the way we approach the

problem of cervical cancer, but even with all of our medical advances, there is so much more work to do. Women need more education about cervical cancer and the associated risk factors, including this link with HPV.
5

Our challenge now is to provide those who have been slow to

seek out screening, very often low-income women, with screening

opportunities and with access to treatment. And so, just this week,

I was honored to join with Congresswoman Anna Eshoo and Congressman Rick Lazio in introducing the Breast and Cervical Cancer

Treatment Act. This bipartisan bill gives States the option to provide Medicaid coverage to uninsured or underinsured women who

have been diagnosed through the National Breast and Cervical

Cancer Early Detection Program, a screening program for low-income, uninsured, or underinsured women. Women who are

screened through this program often cannot afford treatment. All

of the screening in the world won’t help if women who are diagnosed with the disease do not have access to quality treatment for

their condition.

So I look forward to learning more from our experts today as we

seek to raise the awareness of cervical cancer, its causes, and its

treatments. And I hope that we can all work together to enact the

Breast and Cervical Cancer Treatment Act as quickly as possible.

I yield back the balance of my time.

Mr. BILIRAKIS. I thank the gentlelady. Does the gentleman from

Florida, Mr. Stearns, have a quick opening statement?

Mr. STEARNS. A quick opening statement.

Mr. BILIRAKIS. You are recognized.

Mr. STEARNS. Thank you, Mr. Chairman. I appreciate you holding this important hearing, and, of course, I look forward to hearing from our distinguished Senator, who is retiring. I appreciate

the opportunity to see him again.

The average age at diagnosis is 45, but can occur in women 20

to 30 years old. We are not sure what causes cervical cancer, but

we do know that there are a number of pre-disposing factors. These

include multiple sex partners, early sexual activity, and early child

bearing. But the good news is that routine Pap smears are very effective in detecting abnormal cells, and if detected in time, can be

treated with promising results.

I look forward to the hearing, Mr. Chairman, and I appreciate

Senator Mack being here.

[The prepared statement of Hon. Cliff Stearns follows:]

PREPARED STATEMENT OF HON. CLIFF STEARNS, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF FLORIDA

Thank you, Chairman Bilirakis, for holding this very important hearing that deals

with a very serious women’s health issue.

I look forward to hearing from our distinguished panel of witnesses. In particular,

I look forward to hearing from my own Senator, Connie Mack.

When we think about the various cancers that can afflict women, we rarely focus

on cervical cancer. Yet, 2-3 percent of all women over the age of 40 will develop

some form of cervical cancer. That translates to about 5,000 deaths per year.

The average age at diagnosis is 45, but can occur in women 20-30 years old. We

are not sure what causes cervical cancer, but we do know that there are a number

of predisposing factors. These include: multiple sex partners, early sexual activity,

or early childbearing (less than 16 years of age).

Another factor that must be mentioned is that women who were exposed to the

drug DES (diethylstilbestrol) might be at greater risk of developing certain types of

cervical cancer due to this exposure.

The good news is that routine pap smears are very effective in detecting abnormal

cells and if detected in time can be treated with promising results. Because there

are no discernible symptoms in the early stages, it is vital that women see their

physician on an annual basis since early intervention with proper treatment can
6

save 80% of women. Once this disease progresses and spreads to other organs the

survival rate drops significantly.

I look forward to hearing from our witnesses and believe that through hearings

such as this we can educate the public about this disease and the need for medical

check ups on a regular basis.

Mr. BILIRAKIS. I thank the gentleman. Unless it is imperative

that the latecomers make an opening statement, I would like to go

ahead. Greg, do you have a quick opening statement?

Mr. GANSKE. In deference to the chairman, I will submit my

opening statement.

Mr. BILIRAKIS. I appreciate that.

Well, let’s go into the first panel then. Joining Senator Connie

Mack in the first panel is a lady who I always refer to as to the

conscience of this subcommittee. She is a very effective Congresswoman with a fantastic heart. Anna, you are recognized.

STATEMENTS OF HON. ANNA G. ESHOO, A REPRESENTATIVE

IN CONGRESS FROM THE STATE OF CALIFORNIA; AND HON.

CONNIE MACK, A UNITED STATES SENATOR FROM THE

STATE OF FLORIDA

Ms. ESHOO. Thank you very much, Mr. Chairman. Is this on?

Now it is. We are more accustomed to the microphones at the other

side of the table here.

Mr. Chairman and members of the committee, our distinguished

ranking member, it is a special privilege for me to give testimony

today to the subcommittee that I am a member of, and how proud

I am to be a member of the committee. This is an all important

issue, and I think that the entire Nation should be grateful today

that this hearing is taking place.

I am especially proud to be seated next to Senator Mack, and I

want to salute him for his outstanding service in the Congress of

the United States. Everyone will miss your leadership and your

service here. I want to express my gratitude to him and to California Representative Juanita Millender-McDonald for their leadership on the cervical cancer public awareness resolution.

Resolutions are important because I think they set the foundation on which legislation can follow, and so I am very pleased to

be a part of that resolution because it raises public awareness. And

we know that we can make a difference when we set our minds to

it, to raise the awareness of people in the country, and in this case

about cervical cancer, with special regards to its risks, certainly the

prevention, and most importantly, treatment.

Why? Because 70 percent of women in a recent study in our

country did not even know what causes cervical cancer. Less than

a quarter of them had ever even heard of HPV, which is the leading cause of this disease. Cervical cancer is a killer. I should say

that again. Cervical cancer is a killer. Of the 15,000 women who

are diagnosed with cervical cancer each year, 5,000 will die. That

is a huge, huge number of human beings. And we know that we

can do something about this. That is a mortality rate of over 30

percent. In this enlightened Nation, we know we can do better. In

fact, we must.

But even more tragic is the fact that this disease is actually preventable. Since the introduction of the Pap smear, as Congressman

Lois Capps just stated, since 45 years ago, cervical cancer in our
7

country has dropped 75 percent. According to the National Cancer

Institute, the 5-year survival rate is 91 percent when cervical cancer is detected and treated at an early stage.

In 1990, Congress took a very important step. I wasn’t here then,

but to those of you that were, I salute you, because you took a very

important step in the fight against this deadly disease by passing

the Breast and Cervical Cancer Mortality Prevention Act. The law

authorized a cervical cancer screening program for low-income, uninsured, or underinsured women through the CDC. It was a very

important first step, but it was only a first step. Because while the

current program covers screening services, it does not cover treatment for women who are found to be positive through the program.

Representative Rick Lazio, Congresswoman Capps, and myself

introduced last week a bill that would address this. The bill, H.R.

1070, would establish an optional State Medicaid benefit for the

coverage of certain women who are screened and diagnosed

through the CDC program. I don’t really think, Mr. Chairman, that

the Federal Government should be saying to women, ‘‘We are willing to help you be screened and then you are left to your own devices when it comes to treatment.’’ So this is what the bill seeks

to close the gap on.

I set a goal with Representative Lazio when we introduced this

last week—and we missed you, Lois, there, and we understand why

you couldn’t be—that by Mother’s Day we would have 218 co-sponsors on a bipartisan basis in the House. And I hope, Mr. Chairman,

that you will have a hearing on the bill. I think that this is something that we can, indeed, get done for the American people.

So, this providing breast and cervical cancer treatment to women

who cannot afford it otherwise, we believe should be a Federal priority. We know that there is not Republican cancer or Democratic

cancer. When we go home to our constituents, we should have an

united voice and a united front on this.

So, we will look forward to taking the next step, not only on the

resolution, but on the bill, and I want to thank you, Mr. Chairman,

for your leadership always, and our distinguished ranking member,

Sherrod Brown. I think it is the real privilege of my congressional

career to be part of this committee, because we can really make a

difference in people’s lives. So thank you for giving me this opportunity.

[The prepared statement of Hon. Anna G. Eshoo follows:]

PREPARED STATEMENT OF HON. ANNA G. ESHOO, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF CALIFORNIA

Thank you Mr. Chairman. As a member of this distinguished committee, I am extremely proud that we are tackling the issue of cervical cancer. As a witness for the

hearing, I am grateful for the opportunity to contribute my insight into how we, in

Congress, might help to fight this battle.

I also want to express my gratitude to my colleague from California, Rep. Juanita

Millender-McDonald, and Senator Connie Mack for their leadership on the Cervical

Cancer Public Awareness Resolution.

This resolution seeks to raise public awareness of cervical cancer among women,

specifically with regard to risks, prevention and treatment.

• For instance, 70% of women in a recent survey did not know what causes cervical

cancer and less than a quarter had even heard of the human papilloma virus

(HPV), which is the leading cause of the disease.

I am an original cosponsor of the Millender/Mack resolution because I know that

knowledge saves lives.
8

Cervical cancer is a killer.

• Of the 15,000 women who are diagnosed with cervical cancer each year, 5,000 will

die. That is a mortality rate of over 30%.

But even more tragic is the fact that this disease is preventable.

• Since the introduction of the Pap smear test 45 years ago, cervical cancer in the

U.S. has dropped 75%. • According to the National Cancer Institute, the five-year survival rate is 91%

when cervical cancer is detected and treated at an early stage.

In 1990, Congress took the first step in the fight against this deadly disease by

passing the Breast and Cervical Cancer Mortality Prevention Act.

• This law authorized a cervical cancer screening program for low-income, uninsured or uninsured women through the Centers for Disease Control (CDC).

But this was only the first step. While the current program covers screening services, it does not cover treatment for women who are found to be positive through

the program.

A bill Rep. Rick Lazio and I introduced last week would fill that gap.

Our bill, the Breast and Cervical Cancer Treatment Act (H.R. 1070) would establish an optional state Medicaid benefit for the coverage of certain women who were

screened and diagnosed through the CDC program.

Our bill would replace the current system of providing treatment through an ad

hoc patchwork of providers, volunteers, and local programs scrambling to find treatment dollars with a consistent, reliable source of health care coverage.

Mr. Chairman, we have the technology to fight cervical cancer. But we must pair

this with the will to help women fight the battle. Because women with life threatening diseases should be concentrating their energies on treatment, not payment.

Mr. Chairman, the federal government should not be in the business of telling

women, ‘‘We’ve helped you find out you have cancer, now you’re on your own.’’

With over 80 bipartisan cosponsors of the bill already, Congress has sent a message that this bill—the Lazio/Eshoo Breast and Cervical Cancer Treatment Act—

should be a federal priority.

Providing breast and cervical cancer treatment to women who can not otherwise

afford it, should be a federal priority.

So I ask you today, Mr. Chairman, to not allow this to be the only hearing this

subcommittee holds on cervical cancer. Hold a hearing on H.R. 1070 and take the

next step toward helping women fight cervical cancer.

Thank you Mr. Chairman for this opportunity to testify before my own distinguished subcommittee on this very important issue. I look forward to hearing from

the other witnesses.

Mr. BILIRAKIS. Thank you very much.

Ms. ESHOO. I see the red light and I’ll shut my microphone off.

Mr. BILIRAKIS. Thank you very much. Knowing you, Anna, and

having worked with you these many years, I expect you’ll probably

have 218 co-sponsors by your timeline.

It is a great privilege to yield now to Senator Mack.

STATEMENT OF HON. CONNIE MACK

Senator MACK. Well, Mr. Chairman, let me add my voice to others in expressing not only my gratitude for the opportunity to

speak before this committee, but also to thank you for highlighting

this particular issue. Some of you probably remember that I was

diagnosed with melanoma back in 1989, right after I was elected

to the Senate. I don’t have to worry about that today, because it

was detected early. That early detection probably took place because of the death of my younger brother Michael, who died of the

same cancer. It made me so aware of it that I was, as I have said

before, Priscilla and I check each other like two baboons looking

for—you get the message. I am alive today because of early detection.

Many of you know that my wife Priscilla was diagnosed with

breast cancer a number of years ago, and she is a survivor today

because she detected the breast cancer early. Most of you don’t
9

know, in fact, probably all of you don’t know, that our daughter

Debbie was diagnosed with cervical cancer back in 1990. She is a

survivor today because of early detection. She was aware of the

cancers in our family, and as families become sensitive to that,

they are aware of the types of actions they ought to be taking on

their own to protect themselves.

So, I commend you for holding this hearing because, I will tell

you, just as a result of doing the hearing, someone is going to hear

that message. Priscilla and I have already experienced it, and I

suppose that you have as well; that people will come up to you and

say, ‘‘Because I heard such and such, I did such and such, and as

a result today, I am cancer-free.’’

So, I not only commend the chairman, but all of you who have

shown such an interest in this disease. I commend all of you.

According to the American Cancer Society, nearly 1,000 women

in Florida will be diagnosed with cervical cancer in 1999. This year

Florida will have the third largest number of new cases of cervical

cancer.

Yet, despite significant progress being made in the war on cancer, not all segments of the U.S. population have benefited to the

fullest extent from the advances made in the understanding of cancer. According to the U.S. Institute of Medicine report, ‘‘The Unequal Burden of Cancer,’’ rates of cervical cancer are significantly

higher in Hispanic and African-American women. We simply must

do better. We must reinforce our effort to eradicate the terrible disease, but we also must continue and expand our efforts to see that

this information and the knowledge and the education gets to all

women in America.

Research, education, and early detection are the most effective

weapons that we have in the war on cervical cancer. In an effort

to help increase awareness and education about this disease, today

I will introduce a Senate resolution to designate the month of January as National Cervical Health Month. I am pleased that Senator

Diane Feinstein and 31 other members of the Senate have agreed

to be original co-sponsors of this Senate resolution. I know from

what has been said already here this afternoon that Juanita

Millender-McDonald and many of you have agreed to co-sponsor

similar legislation in the House of Representatives.

Research is the key to finding a cure for cervical cancer, and significant progress is being made in this regard. Just last month, for

example, the National Cancer Institute took the rarely used step

of issuing a clinical announcement urging that physicians should

give strong consideration to adding chemotherapy to radiation therapy in the treatment of invasive cervical cancer. According to NCI

Director Rick Klausner, this will likely change the standard of

treatment for cervical cancer. Dr. Mitchell Morris of the M.D. Anderson Cancer Center called this new treatment approach ‘‘the first

fundamental advance in the treatment of cervical cancer in more

than 40 years.’’

Mr. Chairman, I am proud to say that in our home State of Florida, there are several studies that are underway. Scientists at the

University of Miami Sylvester Cancer Center are studying a new

type of cervical cancer immunotherapy. Let me just stop there for

a moment.
10

I guess it was just fate that 1 day, wandering through a bookstore, I saw a book called Transform Cell, and because it was about

melanoma. it caught my attention. I bought the book and read

through it, and as you made your way through it, you found there

were a couple of terms that we really weren’t hearing. Most of us

are familiar with the modalities of chemotherapy, radiation therapy, and surgery as the means of addressing cancer. But there

were a couple of new words that were coming into discussion; that

was immunotherapy. Dr. Rosenberg really believes that we could

turn on the immune system to fight cancer—and that for some reason, the immune system saw cancer cells as just a normal cell in

the body. And so he began an active pursuit, primarily in the area

of melanoma in kidney cancers. The concept now is spreading out

into many other areas.

In addition to immunotherapy, we are hearing people talk about

now gene therapy—again, ideas that just 10 or 12 years ago didn’t

really seem to even be on the horizon. And I think that the Congresses in the past have done a tremendous job in providing the

resources to provide the money for the basic research that creates

the knowledge that then becomes the magnet for investment to develop new drugs and new treatment.

Again, at the Sylvester Cancer Center, they are developing killer

cells specifically designed to target cancer cells which express

human papillomavirus. By eradicating these cells, the hope is to

kill the tumor, even if the cancer has spread.

At the H. Lee Moffitt Comprehensive Cancer Center in Tampa,

studies are underway to develop a cervical cancer vaccine using

some of the same characteristic of the human papillomavirus. They

are also examining biomarkers to develop cervical cancer before

malignant changes occur.

And just in my last comment, and I do take off my Senate hat,

I take off my political hat, I take off a Republican hat, I put them

aside and I just speak to you all for a moment from the perspective

of a father thinking of my daughter Debbie, of a husband thinking

of my wife Priscilla. I say that I am stunned, frankly, by the President’s budget proposal. Last year the administration made a major

commitment to the fight against cancer with a commitment of a 55

percent increase over time. If my memory holds right, I think the

President’s budget calls for a 2, maybe 2.6 percent increase in NIH.

I would ask all of us, again setting aside those labels that I used

a minute ago, let’s rally around. We made a commitment a couple

of years ago for the effort of doubling the investment that we make

at NIH, which is obviously more than cancer. It is Parkinson’s disease; it is sickle cell anemia; you name the disease and we are pursuing it. I think this is the greatest investment that we can make.

So I just would appeal to all of you, let’s re-commitment ourselves

to this commitment we made less than 2 years ago to double the

investment at NIH.

And I thank you again, Mr. Chairman, for the opportunity.

[The prepared statement of Hon. Connie Mack follows:]

PREPARED STATEMENT OF HON. CONNIE MACK, A U.S. SENATOR FROM THE STATE OF

FLORIDA

Mr. Chairman, I want to commend you for holding this important hearing, and

I thank you for inviting me to testify this afternoon.
11

The issue of cervical cancer is one which is deeply personal to my wife, Priscilla,

and to me. In 1990, our daughter, Debbie, was diagnosed with cervical cancer. Because of our family history with cancer, Debbie was aware that she had an increased risk of cancer and she made sure to take advantage of early detection

screening procedures. Fortunately, her cervical cancer was detected at an early

stage, and she was treated successfully with surgery. Not long after her treatment,

she gave birth to our third grandson. Debbie’s experience with cervical cancer exemplifies the fact that early detection saves lives.

According to the American Cancer Society, nearly 1000 women in Florida will be

diagnosed with cervical cancer in 1999. This year, Florida will have the third largest

number of new cases of cervical cancer. Yet, despite significant progress being made

in the war on cancer, not all segments of the U.S. population have benefitted to the

fullest extent from the advances made in the understanding of cancer. According to

the U.S. Institute of Medicine report, ‘‘The Unequal Burden of Cancer,’’ rates of cervical cancer are significantly higher in Hispanic and African-American women. We

simply must reinforce our efforts to eradicate this terrible disease.

Research, education, and early detection are the most effective weapons we have

in the war on cervical cancer.

In an effort to help increase awareness and education about this disease, today

I will introduce a Senate Resolution to designate the month of January as ‘‘National

Cervical Health Month.’’ I am pleased that Senator Dianne Feinstein and 31 bipartisan colleagues in the Senate have agreed to be original co-sponsors of this Senate

Resolution. I understand that Rep. Juanita Millender-McDonald will be introducing

similar legislation in the United House of Representatives.

Research is the key to finding a cure for cervical cancer, and significant progress

is being made in this regard. Just last month, for example, the National Cancer Institute took the rarely-used step of issuing a Clinical Announcement urging physicians to give strong consideration to adding chemotherapy to radiation therapy in

the treatment of invasive cervical cancer. According to NCI Director Rick Klausner,

this will likely change the standard of treatment for cervical cancer. Dr. Mitchell

Morris of the M.D. Anderson Cancer Center called this new treatment approach,

‘‘the first fundamental advance in the treatment of cervical cancer in more than 40

years.’’

I’m also proud to say that several cutting-edge cervical cancer studies are taking

place in my home state of Florida. Scientists at the University of Miami Sylvester

Cancer Center are studying a new type of cervical cancer immunotherapy. They are

developing ‘‘killer cells’’ specifically designed to target cancer cells which express

human papilloma (HPV). By eradicating these cells, the hope is to kill the tumor,

even if the cancer has spread. At the H. Lee Moffitt Comprehensive Cancer Center

in Tampa, studies are underway to develop a cervical cancer vaccine using some of

the same characteristics of the human papilloma virus. They are also examining biomarkers to detect cervical cancer before malignant changes occur.

The U.S. Senate and House, working in bipartisan cooperation, have embarked

upon an historic mission to double funding for the National Institutes of Health over

the next five years. Last year, the Congress overwhelmingly passed, with bipartisan

support, a $2 billion increase for the National Institutes of Health—the largest increase in NIH history.

With the tremendous progress being made in cervical cancer and other diseases,

I was astonished and extremely disappointed the President’s FY 2000 budget only

calls for a meager 2.6% increase for medical research at the NIH. This is simply

unacceptable. The President’s proposed budget means a cease-fire in the war against

cancer, Parkinson’s disease, Alzheimer’s disease and other illnesses. In effect, the

President’s proposal is a formal act of retreat in the heat of battle.

I was also shocked that the President’s FY 2000 budget calls for not one additional penny of funding for the Breast and Cervical Cancer Screening program at

the U.S. Centers for Disease Control & Prevention. For FY 1999, the bipartisan

Congress provided a $16 million increase. By contrast, the President’s request for

FY 1999 was for an increase of less than $1 million for this life-saving program,

and he proposes no increase for next year.

When it comes to cervical cancer research and screening, the President just

doesn’t get it. It’s obvious the leadership on these initiatives will have to come from

this end of Pennsylvania Avenue. It will be through the bipartisan commitment of

the Senate and House that these important research and detection programs will

receive adequate funding. I am here to pledge my support, and to work with my

colleagues in Congress to make sure this happens. Far too many lives depend upon

it.

Again, Mr. Chairman, thank you for holding this important hearing and for allowing me the opportunity to appear before this committee.
12

Mr. BILIRAKIS. And I thank you, Connie.

Yes, I would wager that most of the members of this subcommittee have basically signed on the pledge of doubling NIH

funding, and that is certainly one of our great big causes, working

with John Porter and Bill young on the Appropriations Committee.

Connie, I really have no questions of you and Anna. I just want

to endorse all of the great things that were said about you yesterday in Tallahassee, where we were together for that legislative

summit. Hopefully, you will continue to use your high profile for

this important cause.

Senator MACK. Well, thank you for the encouragement.

Mr. BILIRAKIS. I commend you both for testifying on this important issue.

At this point, I would ask unanimous consent that the opening

statements of all members of this subcommittee and the testimony

of Congresswoman Juanita Millender-McDonald be made a part of

the record. Without objection that will be the case.

[The prepared statement of Hon. Juanita Millender-McDonald

follows:]

PREPARED STATEMENT OF HON. JUANITA MILLENDER-MCDONALD, A REPRESENTATIVE

IN CONGRESS FROM THE STATE OF CALIFORNIA

Mr. Chairman, I would like to thank you, Chairman Bliley, Ranking Member Dingell, and Ranking Member Brown for supporting my efforts to raise awareness of

cervical cancer by serving as original cosponsors of the Cervical Cancer Awareness

Resolution. I would also like to thank all of the Subcommittee members who served

as original cosponsors of this resolution, and in particular, Congressmen Rick Lazio

and Tom Coburn, who have been tireless advocates in our effort to introduce and

pass this resolution to help educate women on this fatal, yet in most cases, preventable disease.

In 1990, Congress passed the Breast and Cervical Cancer Mortality Prevention

Act, which enabled the CDC to establish the National Breast and Cervical Cancer

Early Detection Program. This Program offers community-based screening services

for women with little access to health care, education programs on the benefits of

early screenings, quality assurance standards for cancer testing, and surveillance

system on the effectiveness of these programs.

I applaud the efforts of our colleagues on the Committee who are working to

strengthen these programs and create greater access to screening and treatment for

medically underserved communities. It is this lack of access and poor understanding

of cervical cancer that illuminate the challenge before us today.

More than 50 years ago, Dr. George N. Papanicolaou developed what is considered

the most effective cancer screen in the history of medicine, the Papanicolaou test

or what we call the Pap smear test. Although it is not perfect and we welcome technological advances in the field of medicine, it is a remarkable tool in saving lives

and preventing invasive cervical cancer. The real problem is making sure women

understand what cervical cancer is, what steps they can take to reduce the likelihood of getting cervical cancer, how it can be detected early and what all of their

treatment options are when facing this disease.

As you know, tomorrow Committee Members Lazio and Coburn, and I will introduce the Cervical Cancer Public Awareness Resolution because we want to tackle

this problem of misinformation, confusion and discomfort that too many women continue to feel on this issue. Our resolution is part of a national campaign to raise

awareness on cervical cancer among women and encourage Americans to become

more educated on related risk factors, prevention and treatment.

An estimated 15,000 women in the United States develop cervical cancer each

year according to the American Cancer Society. The World Health Organization and

the National Institutes of Health state that the principal cause of cervical cancer

is the human papillomavirus or HPV infection, which is one of the most common

sexually transmitted diseases (STDs). Fortunately, when cervical cancer is detected

at an early stage, the five-year survival rate is 91 percent, according to the National

Cancer Institute. The Centers for Disease Control and Prevention report that the

mortality rate among American women with cervical cancer declined from 1960 to
13

1997 in large part due to the extensive use of the Pap smear test. However, in 1997

the number began to rise I fear because the message on cervical health has not

reached enough women.

In October 1997, a Gallup survey commissioned by the College of American Pathologists found that although 87 percent of the women surveyed know they should

have a Pap test every year, nearly 40 percent of these same women failed to do so

in the previous year. One in four of the women who had not had an annual Pap

test said they ‘‘didn’t have the time.’’ The reasons include the belief that they are

too old, feeling embarrassed or afraid of tie results, or thinking it is too expensive.

While all of these reasons are valid, they are not acceptable when one considers that

80 percent of the women who die of cervical cancer have not had a Pap test in five

years or more.

As with other health issues, there is a tremendous chasm between minority,

lower-income and/or less educated women as opposed to financially stable, employed

and/or well educated women. According to the Department of Health and Human

Services (HHS), one out of every three Hispanic women reported that they failed

to get a Pap test in the preceding three years, compared with about one-quarter of

all American women. In addition, another survey by HHS on Working Women’s

Health found that 87 percent of employed women had a recent Pap test within the

past 3 years while 73 percent of women not in the labor force had done so. Pap testing for women in managed care plans living in certain regions of the country is also

lower, according to the 1998 State of Managed Care Quality report. For example,

69 percent of women living in the mid-western Mountain states had cervical cancer

screening while 76.5 percent of the women in New England states had cervical cancer screening.

More women of color are dying from this disease as well. For instance, the rate

of mortality for African American women is nearly twice that of Caucasian women

according to HHS. Equally disturbing is the high rate of STD transmission within

this community since HPV is the most common STD. In my own district of SouthCentral Los Angeles, the County Health Department reports that the rates of STDs

among African Americans are up to 20 times higher than among whites and STD

morbidity (except Chlamydia) is concentrated disproportionately in Central and

South-Central LA. HPV infection and cervical cancer are serious risks for the innercity communities I represent.

That is not to say that HPV infection is the only cause of cervical cancer, but

rather, an important part of this health problem that is far too often misunderstood

by women. According to the National Cancer Institute, other risk factors include

smoking although it is not clear exactly how or why. Women whose mothers were

given the drug diethylstilbestrol (DES) during pregnancy to prevent miscarriage

from approximately 1940 to 1970 are at increased risk as well. There is also evidence indicating that women whose immune systems are weakened as a result of

an organ transplant where drugs are administered to prevent rejection of the new

organs are at higher risk.

Although the risk factors for cervical cancer can vary, the cultural, financial and

even geographical barriers that complicate the fluid delivery of quality health care

linger as a dangerous indication of the need for open and honest dialogue on this

issue. As Members of Congress already in the public eye of our communities, we

should do our part in raising public awareness on this critical issue.

Mr. Chairman, I applaud your work today and appreciate your giving me the opportunity to work with you in meeting this goal. Once again, I thank you for your

support of the Cervical Cancer Public Awareness Resolution and I look forward to

working with you to advance this cause.

[Additional statements submitted for the record follow:]

PREPARED STATEMENT OF HON. RICK LAZIO, A REPRESENTATIVE IN CONGRESS FROM

THE STATE OF NEW YORK

Mr. Chairman, one of my priorities as a Congressman is to fight cancer by bringing attention to this dreaded disease. We must find solutions for the women and

men in our country who suffer from all forms of cancer.

I founded the House Cancer Awareness Working Group, a bipartisan working

group which provides an educational forum where cancer patients, advocates, and

scientists can heighten public and congressional awareness and offer recommendations to address the most pressing issues in the battle against cancer. We have focused on issues such as determining the best age for mammography screening, detecting prostate and ovarian cancer, preventing the onset of cancer through healthy

eating, the cancer disparities between races and ethnic groups, the progress of ge-
14

netic research, and the need for anti-discrimination legislation. Gaining the recognition of more than 40 Members of Congress, as well as the American Cancer Society

and the National Cancer Institute, the Group will continue to fight cancer here in

Congress.

In addition to the Working Group, I have recently re-introduced my legislation,

The Breast and Cervical Cancer Treatment Act of 1999. This legislation will complete the CDC’s National Breast and Cervical Cancer Early Detection Program

(NBCCEDP) by adding a treatment component to the extremely successful screening

program for low-income women who have little or no health insurance. We encourage early detection and screening, but treatment must be coupled with screening if

we are ever going to save lives.

My legislation, introduced with Ms. Eshoo, would create an optional state program to allow these women to be covered under Medicaid while they are being treated for cancer. The hallmark of fairness is to ensure that women stricken with cancer

can have the hope of a cure. This legislation is the right thing to do and I hope

that every member of this committee will support it through cosponsorship.

Also, I have recently partnered with Rep. Millender-McDonald and Rep. Coburn

in introducing a cervical cancer resolution recognizing the severity of the issue of

cervical health and its relation to cancer as well as encouraging public awareness,

education, and early detection.

Mr. Chairman, thank you for having this hearing. I look forward to working with

you in taking the appropriate steps to combat this dreaded disease in every way we

know how!

PREPARED STATEMENT OF HON. TOM BLILEY, CHAIRMAN, COMMITTEE ON COMMERCE

Mr. Chairman, I applaud you for holding this hearing today on the issue of cervical cancer. I am proud to say this Committee is the first committee to hold such

a hearing on this issue. I have worked very hard over the years to pass legislation

of importance to public health and especially those related to the special health concerns of women. For example, I recently sent a letter to Dr. Richard Klausner, Director of the National Cancer Institute (NCI), on the importance of health issues,

specifically in regards to women’s health. One issue that I addressed was cervical

cancer. In the response to my letter, NCI stated there are 5,000 women who die from cervical cancer each year. In addition, thousands of others are diagnosed with the disease and begin treatment. In light of these alarming numbers, it is somewhat surprising the lack of attention given to cervical cancer in comparison to other diseases.

A recent study by Wirthlin Worldwide indicated 70% of the women they surveyed

did not even know what causes cervical cancer. Today, we have the sound medical

evidence that demonstrates that human papillomavirus or ‘‘H-P-V’’, while not the

only cause of cervical cancer, is the primary cause of cervical cancer. It is important

that we have this hearing today to raise the awareness of cervical cancer and provide much needed information on the disease.

There are many new advances being made in cervical cancer detection, prevention

and treatment. Today, we will hear about some of the new advances and treatments

that are being made in the fight against cervical cancer. Until the day that cervical

cancer becomes a disease of the past, we need to do all we can to make sure women

know about cervical cancer, its causes and its treatments.

I would like to welcome all of our panels here today to testify. I would especially

like to welcome Sen. Connie Mack for being with us today and for all of his efforts

in the fight against cancer. In addition, I would like to thank Rep. Anna Eshoo, a

member of this subcommittee, for appearing before it today. Thank you all for coming and testifying before us today.

PREPARED STATEMENT OF HON. HENRY A. WAXMAN, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF CALIFORNIA

Mr. Chairman, it is a pleasure to see this Subcommittee return to such an important issue. This is an area of public health where the Subcommittee has been aggressive and successful in enacting important legislation benefitting women’s health.

In 1988, Congressman Dingell and I sponsored the Clinical Laboratory Improvement Amendments of 1988 (CLIA), which protects women from substandard Pap

smears. In 1990 and 1993, I sponsored laws creating and strengthening the Federal

government’s programs to screen, prevent and treat breast and cervical cancers—

the Breast and Cervical Cancer Mortality Prevention Act of 1990 and the Breast

and Cervical Cancer Amendments of 1993.
15

At the time, we believed that these laws would help reduce cervical cancer’s mortality. We funded comprehensive screening programs for low-income women, established quality guidelines for cytological screening, and supported health training

and public education.

There are indications that these efforts, in conjunction with improvements in diagnosis and treatment, have borne some fruit. Deaths and the incidence of cervical

cancer appear to have marginally declined in this country.

But we must do much more. In 1990, cervical cancer caused 6,000 deaths. Last

year, it caused 4,800 deaths—most of them preventable with proper screening and

treatment. Despite the availability of such services to low-income women, there is

evidence that this is not as widely known as it should be. That is why I strongly

support Congresswoman Millender-McDonald and my colleagues on this Subcommittee for sponsoring the cervical cancer awareness resolution.

To save more lives, the next step for the members of this Subcommittee and the

Congress will be to determine whether Federal funding and reimbursement for preventive screening and follow-up treatment is adequate.

I join my colleagues in welcoming our witnesses and look forward to their testimony.

PREPARED STATEMENT OF HON. GENE GREEN, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF TEXAS

I want to thank Chairman Bilirakis for scheduling this important hearing so that

we can learn more about how to prevent and treat cervical cancer.

Each year in the United States, 15,000 women are diagnosed with and 5,000

women will die from cervical cancer.

In fact, it is the second most common form of cancer effecting women today.

The good news is that we have learned a great deal about what causes cervical cancer. The bad news is that there is no cure when it is not detected early on.

With this in mind, there are several steps that Congress can and should take to

help reverse this trend.

First, we need better education of the health risks and behaviors that can help

prevent cervical cancer.

Statistics indicate that while 93% of women with cervical cancer had the sexually

transmitted disease HPV, the overwhelming majority of women have never heard

of HPV—not to mention how to prevent it.

Second, federal health insurance programs should cover not only the screening to

detect and diagnose cervical cancer—but also financial assistance to treat the

women who test positive for this disease.

The federal government should lead by example when it comes to providing the

most comprehensive health insurance for women.

Finally, we need to continue to increase funding for research by doubling the NIH

budget.

Increasing research at NIH will give the thousands of women who are annually

diagnosed with cervical cancer the best chance at finding a cure.

I look forward to hearing from our distinguished witnesses. Before Congress can

help educate our constituents, we need to be fully aware ourselves.

PREPARED STATEMENT OF HON. JOHN D. DINGELL, A REPRESENTATIVE IN CONGRESS

FROM THE STATE OF MICHIGAN

I applaud Mr. Bilirakis for scheduling this hearing on the important issue of cervical cancer. I also would like to applaud the bipartisan efforts of my colleagues in

sponsoring H. Con. Res. 5, a resolution to promote public awareness of cervical cancer. This resolution points out the serious problems associated with cervical cancer

and calls on the country as a whole to learn more about this disease through public

awareness and education.

Last year, H.R. 4683, the Women’s Health Research and Prevention Amendments

of 1998, did not address certain important issues that affect women’s health such

as sexually transmitted diseases. Left untreated, sexually transmitted diseases can

cause infertility, birth defects, disease, and can ultimately lead to death.

Perhaps now we can begin open, frank discussions of this topic since the primary

cause of cervical cancer is one of the most common sexually transmitted diseases,

human papillomavirus (‘‘HPV’’). Up to 80 percent of women develop HPV at some

point in their lives. HPV is unique in that it is largely asymptomatic, can cause cancer, and is so widespread.
16

Each year, an estimated 15,000 cases of cervical cancer are diagnosed, and 5,000

women die from this disease. Even though the incidents of death are lower when

compared to other cancers, the impact of cervical cancer is felt worldwide. It is the

leading cause of death among women in developing countries. The sad part about

this is that most of these deaths are preventable.

The pap smear is the most effective tool for detecting cervical cancer; however,

in many cases the results are inconclusive. Studies indicate that testing for HPV

may be a more effective test for cervical cancer than pap smears. Regular pap

smears combined with HPV testing would be a woman’s best defense against cervical cancer.

I am pleased that my colleagues in the majority on this committee have shown

interest in this important issue. We must raise awareness about cervical cancer if

we are to stop women from needlessly dying from this curable disease. Let this

hearing be a first step in enacting legislation that will ensure that the issue of cervical cancer receives the attention that it deserves. None of us should be satisfied

until the cervical cancer death rate drops to zero.

Thank you.

Mr. BILIRAKIS. Call forward the second panel: Dr. Ronald

Valdiserri, Deputy Director, Center for Disease Control and Prevention; Dr. Nancy Lee, Associate Director for Science, also with

the Center for Disease Control and Prevention; Dr. Douglas Lowey,

Deputy Director, National Cancer Institute, and Dr. Edward

Trimble, Head Surgery Section, National Cancer Institute.

Welcome to this hearing. I apologize for the late start. Often

when we’re scheduled for a hearing, votes take place on the House

floor, and that is why we were delayed in getting here.

Your written statements are a part of the record, and I would appreciate it if you could stay as close to the 5-minute light as you

can in the process of complementing your written statement.

Dr. Valdiserri, we will start off with you.

STATEMENTS OF RONALD O. VALDISERRI, DEPUTY DIRECTOR,

CENTER FOR DISEASE CONTROL AND PREVENTION; NANCY

C. LEE, ASSOCIATE DIRECTOR FOR SCIENCE, CENTER FOR

DISEASE CONTROL AND PREVENTION; EDWARD L. TRIMBLE,

HEAD SURGERY SECTION, NATIONAL CANCER INSTITUTE;

AND DOUGLAS R. LOWEY, DEPUTY DIRECTOR, NATIONAL

CANCER INSTITUTE

Mr. VALDISERRI. Good afternoon, Mr. Chairman and subcommittee members. I am Ron Valdiserri, Deputy Director of the

National Center for HIV, STD, and TB Prevention at the Centers

for Disease Control and Prevention. I thank you for the opportunity

to testify today about what we know about the relationship between human papillomavirus infection and cancer of the uterine

cervix.

Human papillomavirus, otherwise known as HPV, is a virus that

infects the skin and mucus membranes. New laboratory techniques

to identify HPV became available in the 1980’s and revolutionized

what we know about the epidemiology of HPV infection. Over 80

different types have been identified. Some viral types infect the

hands and feet, causing common warts, while others are sexually

transmitted and affect the genital area. Of the 30 or so types that

infect the genital region, some cause clinically apparent genital

warts and also low-grade Pap smear abnormalities, but are not associated with cervical cancer; hence, they are termed low-risk

types. Approximately 10 types are considered high risks for cancer,

in that they are found in approximately 95 percent of all tissue

specimens from cervical cancer patients.
17

It should be stated, however, the genital HPV infections, while

they are not curable, that the vast majority are benign. Definitive

studies on prevention strategies, including male and female

condoms and newly developed microbicides, are, unfortunately,

very limited. Most people who are infected with HPV are asymptomatic and do not develop warts. Infected men and women who

develop genital warts are diagnosed by their typical appearance,

usually without laboratory verification of the virus. Most women

with HPV are diagnosed indirectly by Pap smear or by biopsy findings rather than having the HPV directly detected.

It is estimated that at least 50 percent of sexually active adults

will acquire genital HPV infection. As many as 45 million Americans may already be infected, and an estimated 5 million new cases

develop each year, making HPV the most common sexually transmissible disease. Again, more than 90 percent of people with HPV

infections do not have symptoms, although they are potentially infectious.

Key risk factors for cervical HPV infection in women include a

younger age and the number of sex partners. Cigarette smoking

and oral contraceptive use have also been cited as risk factors. Unfortunately, risk factors for HPV in men have not been very well

studied.

In most sexually active women who acquire HPV infection of the

cervix, the virus becomes undetectable over time without specific

treatment and causes no problems. However, for women whose infections persist, these women are more likely to be infected with

the cancer-associated HPV types. Approximately 5 to 10 percent of

women with the high-risk types of HPV infection will develop cervical cancer without Pap smear screening and early treatment.

Large studies comparing women with cervical cancer to those without it have shown that infection with one of these high-risk HPV

types increases the risk of cervical cancer by at least 30-fold, a

level similar to or higher than the risk of lung cancer association

with cigarette smoking.

Laboratory and animal experiments also support a causative role

for HPV and cervical cancer. In summary, there is now widespread

consensus among cancer researchers that high-risk types of genital

HPV play a causative role in cervical cancer and probably other

types of anogenital cancer, including cancer of the penis and anus.

Having HPV seems to be necessary for developing cervical cancer,

but just having the infection alone is not sufficient to produce cancer. Other co-factors such as smoking, an abnormal immune system, and other genital track infections may also be important. My

CDC colleague, Dr. Nancy Lee, will present an overview of cervical

cancer screening programs later during this panel.

The recognition that cervical cancer is caused by a highly prevalent STD has important implications for public health. Vaccine development is a promising prevention strategy, and my NIH colleague will be discussing this issue. But even before the development of a vaccine, we can prevent cervical cancer in women who

are already infected with HPV. For example, it may be possible to

use HPV DNA tests as an adjunct to the Pap smear to improve the

latter’s accuracy. Studies are now underway to determine if these
18

combined modalities would help to identify women who might otherwise be missed by Pap smear alone.

Several studies have also reported that providing HPV testing for

these women can help determine who is likely to have a more serious problem, and so these tests might be combined with Pap smear

screening to provide a triage of sorts to identify these individuals.

CDC is involved in a variety of research and programmatic activities related to HPV and cervical cancer. However, additional important activities must be undertaken. These include determining

the clinical usefulness of HPV tests and their relative costs and

benefits, developing appropriate counseling messages for women

who learn that they have a cancer-associated STD, evaluating the

effectiveness of various primary prevention strategies, and developing systems to track transient HPV.

Thank you for the opportunity to bring this important public

health issue to your attention, and I will be glad to answer any

questions that you might have.

[The prepared statement of Ronald O. Valdiserri follows:]

PREPARED STATEMENT OF RONALD O. VALDISERRI, DEPUTY DIRECTOR, NATIONAL

CENTER FOR HIV, STD, AND TB PREVENTION, CENTERS FOR DISEASE CONTROL AND

PREVENTION, DEPARTMENT OF HEALTH AND HUMAN SERVICES

HUMAN PAPILLOMAVIRUS INFECTION AND CANCER OF THE CERVIX: WHAT DO WE KNOW

AND WHAT ARE THE IMPLICATIONS?

I am Dr. Ronald O. Valdiserri, Deputy Director of the National Center for HIV,

STD, and TB Prevention at the Centers for Disease Control and Prevention (CDC).

Thank you for the opportunity to present what we know about the relationship between human papillomavirus (HPV) infection and cancer of the cervix which was

one of the most common cancers among women in this country prior to the introduction of Pap smear screening and remains one of the most common cancers worldwide. For more than a century, there have been suspicions that cancer of the cervix

is caused by an infectious agent and behaves like a sexually transmitted disease

(STD). For example, epidemiologic studies have consistently shown that cervical

cancer is rare in virgins but much more common in women who are sexually active

and at risk for other STDs—especially so in women who became sexually active at

a young age, who have multiple sexual partners, or who have sexual contact with

a man who has had multiple partners.

Over the past 50 years, there have been many studies attempting to assess

whether a particular infection—such as gonorrhea, syphilis, chlamydia, or genital

herpes—was the sexually transmitted agent that led to cervical cancer. Many of

these studies cast suspicion on one or more of these infections, but the results remained inconclusive until the 1980s when, using newly developed laboratory techniques, evidence began to point to another, less well understood, STD: the human

papillomavirus or HPV. Prior to that time, HPV was known to cause non-sexually

transmitted warts at body sites such as the hands or feet, as well as sexually transmitted warts around the genitals. But because warts were rarely found on the cervix, it was thought unlikely that HPV could be playing a role in causing cervical

cancer. The inability to recognize cervical HPV infection was in large part due to

the problem that, unlike most other STD organisms, there was and still is no way

to culture HPV in the laboratory.

The development of laboratory tests for detection of HPV/DNA, the genetic material of the virus, helped to overcome this problem and dramatically increased our

estimate of just how frequent HPV infection of the cervix and other genital sites actually occurs. It is now estimated that approximately 5,000,000 new cases of genital

HPV infection occur in the United States each year, making it the most common

of all of the STDs. It is further estimated that at least 50 percent of sexually active

men and women will acquire genital HPV infection at some point and that as many

as 45,000,000 Americans may already be infected. As with many STDs, most of

these infections are asymptomatic, so that the majority of those with genital HPV

are unaware of their infection—further contributing to its spread. The economic burden resulting from these millions of infections has not been clearly determined, but
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is likely quite large. One recent estimate by the Institute of Medicine was over $3

billion per year, more than that for any other STD apart from HIV infection.

The HPV DNA tests have revealed that there are many different strains or types

of HPV; more than 80 types have been identified. Approximately 30 of these are

found primarily in the genital area and are considered ‘‘genital HPV’’. While some

of these 30 types are considered ‘‘low-risk,’’ primarily causing genital warts and lowgrade Pap smear abnormalities, approximately 10 of these types are considered

‘‘high-risk’’ for cancer in that they are found in approximately 95 percent of all tissue specimens from cervical cancer. Large epidemiologic studies comparing women

with cervical cancer to those without it have shown that, even when controlling for

other factors that might make cervical cancer more likely, being infected with one

of these high-risk HPV types increases the risk of cervical cancer by at least 30-

fold, a level similar to or higher than the risk of lung cancer from smoking. In addition to these human studies, laboratory experiments provide additional support that

HPV causes cervical cancer, by showing that when inoculated into cell culture systems, HPV causes the cells to grow in an ‘‘out-of-control’’, cancer-like fashion and

that these out-of-control cells can then cause cancer when injected into mice. Thus,

while definitively proving that an infectious agent causes a disease can be quite difficult, based on a large number of studies, there is now widespread consensus

among cancer researchers that high-risk types of genital HPV clearly play a causative role in the development of cervical cancer, and probably other types of

anogenital cancer, such as cancer of the penis and anus.

Having HPV seems to be ‘‘necessary’’ for developing cervical cancer, although having the infection alone is not ‘‘sufficient’’ to produce cancer, and other co-factors such

as smoking, an abnormal immune system, and other infections may be important

as well. The role of the immune system has been most clearly demonstrated in patients with HIV infection in whom very high rates of HPV infection occur and in

whom both cervical and anal cancer appear to be increased. Although a large proportion of sexually active women will become infected with genital HPV, the majority of these infections become undetectable over time without specific treatment or

the development of complications. Only those women whose infection persist are at

risk for developing cancer, and it has been estimated that approximately 5-10 percent of women with high-risk types of HPV infection will develop cervical cancer.

Pap smear screening programs and early treatment reduces this percentage even

further.

The recognition that this important cancer is caused by a highly prevalent STD

has important implications for public health. The first strategy to consider is that

of primary prevention, namely, preventing cancer by preventing infection. Unfortunately, the traditional STD control strategy of preventing transmission by identifying infected persons and then treating them and their partners in order to prevent

transmission to other partners currently has limited value for viral STDs such as

HPV because existing therapies do not cure infection. The therapies available for

both genital warts and cervical HPV infection will eradicate the tissue abnormality,

but probably do not eliminate the infection entirely. Abstinence should be effective

for preventing HPV infections, since the large majority are sexually transmitted.

However, other approaches to prevent HPV infection are also promising. Latex

condoms can be expected to be protective if they cover the genital skin that is infected and if they are used consistently and correctly. Several studies have shown

condoms to provide some protection against cervical cancer, and the more recently

developed female condom has promise as a physical barrier in the prevention of

viral STDs because of its greater surface area.

Microbicides, chemicals that inhibit microbial growth and could potentially function as ‘‘chemical barriers’’ also have potential benefit. Some of these agents currently under investigation have been shown to inactivate genital HPV in the laboratory. Advantages of microbicides include both the possibility of inhibiting multiple

STDs—such as HPV and HIV—with one agent, and providing a protective strategy

under the control of the woman, in contrast to male condoms.

The most promising primary prevention strategy would be the development of an

HPV vaccine. There are several animal models in which papillomavirus infections

specific to the particular animal can be effectively prevented by immunization,

which has created great optimism that vaccines against HPV might be beneficial in

humans as well.

Several small studies are now underway in humans to determine whether the experimental HPV vaccines are sufficiently safe and effective at producing an immune

response to warrant larger, more definitive studies. Because of the relatively large

number of high-risk HPV-types believed to cause cervical cancer, effective vaccines

will have to contain multiple types of HPV to achieve high levels of benefit, which

increases the complexity and length of time it will take to develop and test them.
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Such preventive vaccines would ideally be given prior to the onset of sexual activity

probably in early adolescence since most people who contract genital HPV infection

do so within the first several years of sexual activity. Because the peak incidence

of cervical cancer are between 35 to 55 years of age, it would likely be at least 20

years after the initiation of vaccine programs before we would see reductions in cancer rates. However, effective vaccines would also reduce the rate of pre-cancerous

Pap smear abnormalities, known as dysplasia. Considering that the evaluation and

treatment of dysplasia is among the most expensive aspects of the current cervical

cancer prevention efforts, reductions would most likely occur much earlier in cost

as well as the avoidance of anxiety that often accompanies the diagnosis of an incurable STD or pre-cancerous changes on a Pap smear.

Our current strategy is to prevent cancer in those who already have HPV infection. In essence, this is what Pap smear screening is directed toward—the early detection of pre-cancerous changes caused by HPV infection which can be evaluated

and treated to prevent their progression. With the knowledge that HPV infection

causes cancer, it may be possible to use HPV/DNA tests as an adjunct to the Pap

smear to improve its accuracy. A single Pap smear does not identify all women who

have serious abnormalities, so serial Pap smear screening is the current standard

of care. Studies are underway now to find out if using HPV/DNA tests, along with

the Pap smear, will increase the test sensitivity (in other words, the likelihood of

identifying women with abnormal Pap smears). If these tests work well enough,

they might not only prevent women with treatable problems from being missed,

they might also allow Pap smears to be done less frequently than annually in most

women, thereby reducing costs of screening. Furthermore, because samples for HPV

testing are easier to collect than Pap smear samples, they may permit the development of self-collected swab kits for women, which, by avoiding the need for a full

gynecologic exam, might be more convenient for many women and could encourage

many more women to get tested for HPV. Such self-collected testing also facilitate

development of outreach efforts, where field workers go into non-clinic locations to

do testing, similar to approaches that have been used for community-based programs to address high blood pressure, high cholesterol, tuberculosis, and even STDs

like chlamydia.

An even more immediate use of HPV tests for secondary prevention is their use

to triage women with low-grade Pap smear abnormalities. Currently, the large majority of women in the United States with abnormal Pap smears have early changes

that have a very low risk of progression to cancer, and yet, to be sure an important

problem isn’t missed, these women usually need to come back for several follow-up

examinations, creating tremendous anxiety and expense. Several studies have reported that providing HPV testing for these women can help determine who is likely

to have a more serious problem. If these reports can be confirmed by larger studies

now underway, they may permit a more cost-effective approach to this very common

problem.

Important work remains to be done before these strategies will be ready for widespread implementation. CDC is currently involved in a number of applied research

and service activities to improve prevention of genital HPV infection and cervical

cancer. Among these are:

• studies of the epidemiology and natural history of HPV infection and cervical cancer.

• studies to better define approaches to clinical use of HPV tests.

• studies to assess HPV-related complications in patients with HIV infection.

• studies to determine mechanisms by which HPV causes cervical cancer.

• development and assessment of improved HPV tests.

• implementation of a pilot national population-based serosurveillance study to

more accurately assess the extent of genital HPV infection.

• support of health care provider training programs regarding both cervical cancer

and genital HPV infection.

• development of clinical practice guidelines for genital HPV infection.

• education of the general public through the CDC National STD Hotline

• implementation of the National Breast and Cervical Cancer Early Detection Program that provides access to cancer screening and follow-up for underserved

women.

• development of the National Program of Cancer Registries that will enhance surveillance of cervical and other HPV-related cancers. Currently, serious gaps in

our knowledge preclude the formulation of more effective prevention strategies

for genital HPV infection and cervical cancer:
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HPV Testing

• If the ongoing studies to assess use of HPV tests for triage of women with lowgrade Pap smear abnormalities find this to be a helpful strategy, we must determine if this approach works equally well in all groups of women. For example, because younger women have much higher background rates of HPV infection than do older women, HPV testing may be too non-specific (i.e. likely to

test positive when no serious abnormality really exists) to be helpful in the

younger group, and could turn out to be a ‘‘double-edged sword’’, creating more

anxiety and costs than it saves. • Studies to assess the use of HPV tests as an adjunct to Pap smear screening will

also need to demonstrate which groups of women (such as younger vs older) get

the most benefit from this extra test. • As ‘‘self-test’’ kits are developed, program evaluations will be necessary to find

out how best to distribute them and encourage their use. Any use of such HPV

tests will require the development of approaches both to counsel women who

suddenly discover that they have a cancer-associated STD, and to evaluate their

sexual partners.

HPV Vaccine Development and Use

• The development of effective HPV vaccines would be enhanced by collection of additional surveillance data on the prevalence of different types of HPV infection

in different groups of men and women, both to determine exactly which types

of HPV a final vaccine should contain and to track early benefit of vaccines once

they are licensed and widely used. • There is virtually no experience in ‘‘marketing’’ vaccines for prevention of STDs

and cancer to the general public or to health care providers. Yet for HPV vaccines to achieve their promise, their use will need to be as widespread in the

population as is the virus. Sexually active persons in all socioeconomic groups

are at risk for HPV infection; thus, immunization of all persons who will potentially be sexually active in the future would likely be the most effective prevention approach. Behavioral and social marketing research to explore this issue

will be important and such research may also have benefit for other STD vaccines, including those for HIV. • To the extent that effective HPV vaccines are developed and utilized and Pap

smear abnormalities prevented, approaches used in Pap smear screening programs will also likely evolve, since criteria for what constitutes a suspicious

smear may change as certain types of HPV infection are prevented.

Assessment of Non-Vaccine Strategies for Primary Prevention

• Pending the availability of effective vaccines, a better understanding of how well

other primary prevention strategies may work is important. Understandably,

one of the major concerns of patients diagnosed with genital HPV infection is

how to prevent it from being transmitted to sexual partners, an issue that will

only increase if clinical use of HPV testing becomes more widespread. To this

end, better information is needed to determine how long someone with genital

HPV is contagious to a sexual partner and which prevention strategies work

best to prevent transmission.

Programs to Assess Burden of Infection

• Monitoring systems to provide information about rates of various types of Pap

smear abnormalities and of type-specific genital HPV infections in targeted populations will be important in planning and evaluating vaccine programs, as well

as in tracking the distribution of HPV infection in the population. Such studies

may be particularly useful in clarifying rates and types of infections in men

about which far less is known than for infections in women. • Economic assessments of the costs resulting from HPV infection are limited and

not available for all populations. Furthermore, existing analyses address only

direct medical costs (the costs of actually providing care), and there is virtually

no information on indirect costs (those resulting from lost productivity or premature death of someone with a medical problem) or intangible costs (such as

anxiety and distress in personal relationships). Such information is critical in

determining the potential public health and societal benefit of various prevention programs.

Programs to Increase Public and Health Care Provider Awareness

• While better understanding of the prevalence of HPV and its relationship to cancer will support better prevention efforts, messages to educate the general public about HPV will need to be clearly crafted to avoid undue anxiety, competition with other public health prevention messages, and the possibility because
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of the stigma associated with STD and undermining Pap smear screening programs.

• The issues around HPV are complex ones for health care providers who must convey messages that are both accurate and helpful to patients with concerns, often

in time-constrained clinical settings. In addition, because genital HPV infection

is a minor health problem for the vast majority of infected people, proper education and counseling may be as important as treatment. More cost-effective

means to convey this information is an important priority.

In April, 1999, CDC and the American Cancer Society will convene a pivotal

meeting of national and international experts, including our NIH colleagues, to review possible prevention strategies and prevention research needs for genital HPV

infection and its complications. The goal of this meeting is to develop priorities for

a linked programmatic and research agenda for CDC and other public health agencies.

Mr. BILIRAKIS. Thank you very much, Dr. Valdiserri.

Dr. Lee?

STATEMENT OF NANCY C. LEE

Ms. LEE. Good afternoon, Mr. Chairman and the subcommittee

members. Can you hear me? I am Dr. Nancy Lee, Associate Director for Science at the Division of Cancer Prevention and Control at

the CDC in Atlanta. I am pleased to be here this afternoon to discuss how CDC approaches cervical cancer early detection through

the National Breast and Cervical Cancer Early Detection Program.

As discussed in the previous presentation, infection with certain

strains of HPV is one of the strongest risk factors we know for cervical cancer. But the most important risk factor for developing cervical cancer, at least from the point of view of what we can do

about it now, is the failure to receive regular screening with a Pap

smear.

Cervical intraepithelial neoplasia or CIN is the pre-cancerous

condition that can develop into cervical cancer. With appropriate

treatment, almost all women diagnosed with CIN should be cured

of their condition. From the time a women develops CIN, it usually

takes years before cervical cancer develops. So we have many opportunities to detect pre-cancerous lesions with regular Pap screening, treat them, and actually prevent cervical cancer. Furthermore,

even if cervical cancer has developed, when detected at its earliest

stage, the 5-year survival is over 90 percent.

The accepted screening test for cervical cancer is the Pap smear.

Since introduction 50 years ago, the Pap smear has been credited

with the steady decline in cervical cancer deaths in the United

States. In 1994, well over 90 percent of all women had received a

Pap test at least once in their lives, and 80 percent had one within

the preceding 3 years.

In 1990, as many of you have spoken already, Congress passed

the Breast and Cervical Cancer Mortality Prevention Act. This act

authorized CDC to establish a nationwide screening program to ensure that low-income women who are uninsured receive regular

screening for breast and cervical cancer.

In fiscal year 1999, with appropriations of $159 million, the CDC

entered into the ninth year of the National Breast and Cervical

Cancer Early Detection Program. CDC supports programs in all 50

States, 5 U.S. territories, the District of Columbia, and 15 American Indian and Alaska Native organizations. The national program has provided more than 1.1 million Pap smears to over
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700,000 women. However, with existing resources, it is able to

screen only 12 to 15 percent of the eligible population annually.

Significantly, almost half of the women screened are from minority

racial and ethnic groups. This is the really good news: More than

31,000 cases of these pre-cancerous lesions have been detected and

only 508 women have been diagnosed with cervical cancer.

This last set of statistics illustrates a key point that I always emphasize when I talk about the program. The main purpose of cervical cancer screening is to find pre-cancerous lesions, treat them,

and cure them so that these women never have to be diagnosed

with cancer.

Our program statistics illustrate the success of Pap testing and

emphasize the proven strategy that can be used to fight this disease. We consider women who do not receive Pap tests to be a priority population. The national program endeavors to provide cervical cancer screening to women who are hard to reach because of

cultural, language, or financial barriers. Our No. 1 goal must be to

reach the largest number of unscreened women as our resources

allow.

For example, many programs are involved with developing low

literacy, bilingual, or culturally appropriate materials that are used

in a myriad of training and outreach programs and educational

campaigns. The various strategies used by different programs promote screening and increase knowledge and awareness of cervical

cancer.

The Food and Drug Administration has approved three new technologies for Pap smears: ThinPrep, AutoPap and Papnet. These

technologies all appear to do a somewhat better job of detecting

cervical disease than conventional Pap tests. They are rapidly

being adapted by laboratories nationwide and at least double the

price of the conventional Pap test. However, there are concerns

that the extra costs associated with these technologies will overshadow their benefits. In spite of the promise of these new technologies, the American College of Obstetricians and Gynecologists

stated last year that their routine use, ‘‘could not be recommended

based on costs and the lack of sufficient data demonstrating whether they reduce the incidence of or improve the survival rate for an

invasive cervical cancer.’’ The College also concluded that the main

strategy should be screening women who are not receiving regular

Pap tests, as they account for the majority of new cervical cancer

cases each year.

CDC is committed to increasing the awareness, availability, and

use of cervical cancer screening services for women. We must also

work hard to screen those women who are not receiving regular

screening, as they are at greatest risk for developing cervical cancer. This is the hardest part of our job, but one we cannot ignore.

The national program will continue to develop strategies to find

those women most in need of the lifesaving benefit of Pap smear

screening.

Thanks for your interest in cervical cancer detection programs at

CDC, and I, as well, am pleased to answer any questions you may

have.

[The prepared statement of Nancy C. Lee follows:]
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PREPARED STATEMENT OF NANCY C. LEE, ASSOCIATE DIRECTOR FOR SCIENCE, NA- TIONAL CENTER FOR CHRONIC DISEASE AND HEALTH PROMOTION, CENTERS FOR

DISEASE CONTROL AND PREVENTION, DEPARTMENT OF HEALTH AND HUMAN SERV- ICES

Good Morning, I am Dr. Nancy Lee, Associate Director for Science, within the Division of Cancer Prevention and Control of the National Centers for Chronic Disease

Prevention and Health Promotion, Centers for Disease Control and Prevention

(CDC) in Atlanta, Georgia. I am pleased to be here this morning to discuss how

CDC approaches cervical cancer early detection through CDC’s, National Breast and

Cervical Cancer Early Detection Program (NBCCEDP).

Background

Cervical cancer is nearly 100 percent preventable, yet according to the American

Cancer Society, an estimated 12,800 new cases of invasive cervical cancer will be

diagnosed in 1999 with about 4,800 women dying of the disease. The cervical cancer

death rate declined 45 percent between the periods 1972-74 and 1992-94 and the

overall incidence of the disease has decreased steadily from 14.2 per 100,000 in 1973

to 7.4 per 100,000 in 1995. This is largely attributed to the effectiveness of Pap

smear screening for cervical cytology.

Even with this success, there remains significant disparities in the incidence and

mortality of cervical cancer among some racial and ethnic minority women, when

compared to the rate in white women. The incidence rate for all U.S. women is

about 8 per 100,000; however, the highest age-adjusted incidence rate of 43 per

100,000 occurs among Vietnamese women, probably reflecting lack of appropriate

screening. Incidence rates of 15 per 100,000 or higher also occur among Alaska Native, Korean, and Hispanic women. The death rate of 6.7 per 100,000 in African

American women continues to be more than twice that of whites even though their

incidence rate is slightly lower.

Early Detection

Cervical cancer occurs at an average age of 54; however, cervical intraepithelial

neoplasia (or CIN), the precursor lesion to cervical cancer, most often occurs in

much younger women. For a woman with CIN, her likelihood of survival is almost

100 percent with timely and appropriate treatment. The fact that CIN occurs at a

younger age tells us that it usually takes a substantial amount of time for cervical

cancer to develop. This means that screening younger women is an important strategy that actually prevents cervical cancer from ever developing. Furthermore, when

cervical cancer is detected at its earliest stage, the 5-year survival rate is more than

90 percent.

Risk Factors

Studies that have identified risk factors associated with cervical cancer have

shown that cervical cancer is closely linked to sexual behaviors, human

papillomavirus (or HPV) infection, immunosuppressive disorders such as HIV/AIDS,

as well as a failure to receive regular Pap smear screening. The sexual behaviors

specifically associated with greater risk are intercourse at an early age, multiple

male sexual partners, and sex with a male partner who has had multiple sexual

partners. Experts agree that infection with certain strains of the HPV is one of the

strongest risk factors for cervical cancer, but the most important risk factor for developing cervical cancer, at least from the point of view of what we can do about

it, is the failure to receive regular screening with a Pap smear.

Screening Tests

The principal screening test for cervical cancer is the Pap smear. Since its introduction 50 years ago by Dr. Papanicolaou, the Pap smear has been widely used and

is credited with the steady decline in cervical cancer deaths in the United States.

Nationwide estimates from 1994 indicated that well over 90 percent of all U.S.

women had received a Pap test at least once in their lives and that 80 percent had

obtained one within the preceding 3 years.

Despite the ability of the Pap test to help reduce cervical cancer mortality, the

test is far from 100 percent accurate. Approximately half of the inaccuracies are due

to inadequate collection of the Pap smear by the health care provider and the other

half are due to errors at the laboratory. Detecting a precancerous lesion such as CIN

does not always mean that a cancer has been prevented because only some of the

early precancerous lesions progress to cancer. Thus, the search for a more efficient

means of screening for cervical cancer and precancer is ongoing.

The Food and Drug Administration has approved three new technologies for Pap

smears: ThinPrep, AutoPap, and Papnet. The technologies all appear to do a some-
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what better job of detecting cervical disease than conventional Pap tests. They are

rapidly being adopted by laboratories nationwide and at least double the price of

the conventional Pap test. However, there are concerns that the extra costs associated with these technologies will overshadow their benefits.

Two evaluations of cervical cytology were released in January: one done for the

Agency for Health Care Policy and Research, and the other published in the Journal

of the American Medical Association. Although the analyses were independently

done, each determined that new screening technologies were cost-effective only if

screening was infrequent, done every 3-4 years. They also found that the new technologies increased life expectancy by a relatively small amount compared with conventional Pap testing.

In spite of the promise of these new technologies, the American College of Obstetricians and Gynecologists stated last year that their routine use ‘‘[could] not be recommended based on costs and the lack of sufficient data demonstrating whether

they reduce the incidence of or improve the survival rate from invasive cervical cancer.’’ The college also concluded that the main focus should remain screening women

who are not receiving regular screening, as they account for the majority of cervical

cancer cases.

Screening Guidelines

There are several different recommendations from national, professional and governmental organizations on the frequency that women should receive a Pap test.

The American Cancer Society, National Cancer Institute, American College of Obstetricians and Gynecologists, American Medical Association, American Academy of

Family Physicians, and others developed a consensus agreement regarding cervical

cancer screening. These organizations recommended annual Pap testing for all

women who have been sexually active, or have reached the age of 18.

After three consecutive annual exams with normal findings, the Pap test could be

performed less frequently at the discretion of the physician.

The U.S. Preventive Services Task Force recommends regular Pap tests for all

women who are or have been sexually active, or who are 18 or older, and who have

a cervix. The Pap test should be performed at least every 3 years. However, the interval for each patient should be determined by the physician, based on the woman’s

history of risk factors.

National Breast and Cervical Cancer Early Detection Program

Recognizing the value of appropriate cancer screening, Congress passed the

Breast and Cervical Cancer Mortality Prevention Act of 1990 (Public Law 101-354).

This Act authorized the Centers for Disease Control and Prevention (CDC) to establish a national screening program to ensure that low income women who are uninsured or underinsured receive regular screening for breast and cervical cancer and

prompt followup when necessary. In fiscal year 1999, with Congressional appropriations of $159 million, the CDC entered into the ninth year of the National Breast

and Cervical Cancer Early Detection Program (NBCCEDP). This landmark program

brings critical breast and cervical cancer screening services to underserved women,

including older women, women with low income, and women of racial and ethnic minorities.

CDC supports early detection programs in all 50 states, five U.S. territories, the

District of Columbia, and 15 American Indian/Alaska Native organizations. The goal

of the national program is to establish, expand, and improve community-based

screening services for women at risk. The goal is achieved by screening medically

underserved women for breast and cervical cancer, providing appropriate and timely

diagnostic evaluations for women with abnormal screening tests and treatment services if needed, developing and disseminating public information and education related to the detection and control of breast and cervical cancer, improving training

of health professionals in the detection of these cancers, and finally, evaluating program activities through the establishment of surveillance systems.

The program targets cervical cancer screening services to women who are hard

to reach and are unlikely to seek a Pap test because of cultural, language, monetary

or institutional barriers. As a major public health program, our overall concern must

be to reach the largest number of unscreened, eligible women as possible. Thus, we

also consider all women who do not receive regular Pap tests a priority population

for the program. Currently, the national program follows cervical cancer screening

guidelines that are consistent with the consensus guidelines developed by the American Cancer Society and others.

Providing cervical and breast cancer health education and outreach services is an

essential component to the NBCCEDP. With technical guidance, our funded programs have developed projects that are focused on specific at-risk populations and
26

cover a wide range of prevention and research activities. For example, many programs are involved with developing low literacy, bilingual and culturally appropriate educational materials that are used in a myriad of unique training and outreach programs and educational campaigns. These various strategies used by the

different programs result in the common goal of increasing knowledge and awareness of breast and cervical cancer and promoting screening for early detection.

CDC partners with many national organizations to address issues related to

breast and cervical cancer screening in priority populations. For instance, CDC

funds the American Social Health Association to formulate a national model for the

prevention of cervical cancer, using two counties in North Carolina as pilot sites and

focusing upon economically disadvantaged Hispanic and African-American populations and women living in hard-to-reach urban and rural areas. This cervical cancer prevention project consists of developing and delivering culturally appropriate

media messages, educational materials, client support services, and health education workshops in the community setting.

CDC is committed to increasing the awareness, availability and use of cervical

cancer screening services for women. The main purpose of cervical cancer screening

is not to find cancer, but to find precancerous lesions. Early detection and treatment

of precancerous cervical lesions identified by Pap screening can actually prevent cervical cancer; thus, the success of any cervical cancer screening program depends on

the early detection, case management and treatment of precancerous cervical lesions.

The breast and cervical cancer program has provided more than 1.1 million Pap

test to a total of more than 700,000 women. With existing resources, the national

program is able to screen 12-15 percent of the eligible population annually. Almost

half of the women screened are from minority racial and ethnic groups. Of Pap tests

provided, about 3 percent were abnormal; more than 31,000 cases of precancerous

lesions were ultimately diagnosed, and 508 women were diagnosed with invasive

cervical cancer. These statistics illustrate a key point for this essential public health

program. The main purpose of cervical cancer screening is to find precancerous lesions, treat them, and cure them, so that these women do not go on to be diagnosed

with cervical cancer. Of all the women diagnosed with cervical disease through our

program, fewer than 2 percent actually had a diagnosis of cancer. The program has

potentially averted cancer in more than 31,000 women! This underscores the success

of Pap testing and emphasizes the proven strategy that we as public health practitioners can use to fight this cancer.

As mentioned earlier, the success of any cervical cancer screening program depends on the early detection and treatment of precancerous cervical lesions. But we

must also work hard to screen those women who are not regularly screened elsewhere. Research has shown that they are at the greatest risk for developing cervical

cancer. This is the hardest part of our job, but one we cannot ignore. The National

Breast and Cervical Cancer Early Detection Program will continue to develop strategies to find those women and provide the life-saving benefit of Pap smear screening.

Thank you for your interest in the cervical cancer early detection activities at

CDC. I would be pleased to answer any questions you may have.

Mr. BILIRAKIS. Thank you very much, Dr. Lee.

Dr. Lowey. Well, all right, Dr. Trimble.

STATEMENT OF EDWARD L. TRIMBLE

Mr. TRIMBLE. Good afternoon, Chairman Bilirakis and subcommittee members. Thank you for inviting us to speak today. I

am an obstetrician/gynecologist and gynecologic oncologist. My responsibility at NCI is the development of a new treatment for

women with gynecologic cancer.

As we have heard, cervical cancer is the third leading cause of

cancer deaths for women around the world. In the United States

the number of cases and deaths have dropped dramatically, primarily due to effective screening and treatment of pre-invasive disease.

As we have heard, more than 90 percent of cases are due to infection with the human papillomavirus, but the vast majority of

men and women who have infection with this virus will face no adverse health consequences.
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The other risk factors that have been identified include cigarette

smoking, a higher number of pregnancies, lower socio-economic status, immunosuppression, multiple sexual partners, a high-risk sexual partner, and an early age of onset of sexual activity.

The treatment for pre-invasive cancer is generally surgery for

those with disease confined to the cervix, and radiation therapy for

women found to have cervical cancer grown beyond the cervix into

the pelvic tissues. The 5-year survival rate for those with disease

confined to the cervix is 90 percent compared to only 50 percent for

those whose disease is found to extend beyond the cervix.

We evaluate new treatment options primarily through the NCI’s

Clinical Trials Cooperative Groups, which bring together doctors

and nurses and patients around the country. Recently, five of these

trials—conducted by the Gynecologic Oncology Group, the Southwest Oncology Group, and the Radiation Therapy Oncology

Group—enrolled 1,900 women with cervical cancer. The results of

these trials showed that chemotherapy given at the same time as

radiation therapy improved survival and decreased the number of

recurrences.

When the NCI became aware of these results, we convened a

jury with doctors and a representative from the patient advocacy

community to review the results. That panel voted unanimously

that the National Cancer Institute should issue a clinical announcement, as Senator Mack mentioned. This announcement was

sent to 14,000 physicians, was placed on the NCI website, and we

also worked closely with the New England Journal of Medicine, to

whom 300 manuscripts were submitted, to speed review and publication of these important results.

We continue to work through our cancer centers, through our cooperative groups, through our grantees, and through investigators

at the National Institutes of Health on ways to improve treatment.

We are working to see whether fertility-sparing surgery can be useful to see if we can improve our chemotherapy and radiation therapy as well as to develop vaccines against the human

papillomavirus.

Dr. Lowey will address the issue of vaccine development in greater detail. We are very excited about his research and that of other

investigators in the field because we have the potential that we

may able to prevent initial infection with human papillomavirus as

well as to improve treatment for women diagnosed with cervical

cancer.

Mr. BILIRAKIS. Thank you, Dr. Trimble.

Dr. Lowey.

STATEMENT OF DOUGLAS R. LOWEY

Mr. LOWEY. Yes, good afternoon, Mr. Chairman and subcommittee members. I am Douglas Lowey. I am the Deputy Director of the Division of Basic Sciences in the National Cancer Institute and also run a research laboratory at the NIH that studies

papillomaviruses. I would like to thank you for the opportunity to

talk with you today about the prospects of developing a vaccine

against HPV infection.

As you have already heard, cervical infection with human

papillomavirus is the most common sexually transmitted infection
28

of women. Abnormal Pap smears and pre-malignant lesions represent a manifestation of this infection, and virtually all cervical

cancers arise as a consequence of infection by these viruses. In addition, there is also evidence that links HPV infection at other sites

in the body to several other types of cancers.

The demonstration that pre-malignant conditions and cancers

are caused by an infectious agent such as a virus implies that a

safe and effective vaccine which could prevent the infection, would

prevent the pre-malignant adnormalities as well as the cancers. It

is also possible that a vaccine directed against the virus might

have therapeutic effects. However, the history of virus vaccines indicates it is much more difficult to develop vaccines that cure established infection than to develop ones that prevent infection.

The principal message I would like to convey today is that we believe real progress is being made toward achieving the goal of developing an effective, preventive vaccine against HPVs involved in

cervical cancer. My reasons for this optimism are based on vaccine

studies of papillomavirus infection in animals, on early phase vaccine trials in normal human volunteers, as well as on the composition of the vaccine. Efforts to develop papillomavirus vaccines with

therapeutic potential are also being pursued, as Mr. Mack mentioned in his testimony.

The preventive papillomavirus vaccine is a subunit vaccine that

is made by genetic engineering techniques analogous to those used

to make recombinant Hepatitis B vaccine, which is widely used in

the United States and elsewhere. The preventive vaccine currently

in human trials is composed of multiple copies of just a single viral

protein which self-assembles to form the outer shell of the virus

particle in a manner that faithfully mimics the structure of this

shell in an infectious virus. However, unlike infectious virus, the

virus-like particles in the vaccine are not infectious since they don’t

contain any papillomavirus genes. Therefore, the vaccine is unlikely to be dangerous for normal individuals.

In animal papillomavirus models, vaccination with the

papillomavirus vaccine has been 90 percent to 100 percent effective

in preventing infection. Several pharmaceutical companies are actively involved in the commercial development of such a vaccine.

Clinical trials are also being carried out by the National Institutes of Health. This represents a trans-NIH effort with important

support from the NIH Office of Research on Women’s Health, the

NIH Office of Research on Minority Health, the National Institute

of Allergy and Infectious Diseases, and the National Cancer Institute.

In humans, although only a little more than 100 individuals have

thus far received the vaccine, it has been well tolerated by those

individuals, and almost everyone who has received adequate doses

of the vaccine has mounted a strong immunologic response against

the vaccine. Such an immune response often correlates with protection against infection, but the early phase trials cannot determine

whether or not the vaccine is effective. These are encouraging results. However, it remains possible that the first generation vaccine

may not be as effective in people as we hope.

If additional vaccine studies in normal individuals over the next

year continue to show promise regarding safety and immune re-
29

sponse, the National Institutes of Health would plan to initiate a

large-scale, placebo-controlled efficacy trial in Costa Rica, a country

with high rates of cervical cancer, where the National Cancer Institute already works closely with a local research team to study HPV

infection in young Costa Rican women.

An efficacy trial will take a few years to complete since the vaccine needs to be evaluated in unaffected women, and its effectiveness can only be learned after HPV has developed in a reasonable

number of those women who receive the placebo. Therefore, even

if the vaccine proves to be effective in trials conducted by the NIH

and by pharmaceutical companies, it will take several years before

the vaccine would become available to the general public.

I am grateful to you for giving me this opportunity to discuss this

issue with you, and I applaud your efforts and your concerns about

cervical cancer and would be happy to answer questions. Thank

you.

[The prepared statement of Edward L. Trimble and Douglas R.

Lowey follows:]

PREPARED STATEMENT OF EDWARD L. TRIMBLE, HEAD, SURGERY SECTION, DIVISION

OF CANCER TREATMENT AND DIAGNOSIS AND DOUGLAS R. LOWY, DEPUTY DIRECTOR, DIVISION OF BASIC SCIENCES, NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH, DEPARTMENT OF HEALTH AND HUMAN SERVICES

Good afternoon. We are Edward Trimble, M.D., Head of the Surgery Section for

Division of Cancer Treatment and Diagnosis and Douglas Lowy, M.D., Deputy Director for the Division of Basic Sciences at the National Cancer Institute. It is our

pleasure to appear today to discuss the progress we are making in cancer research,

specifically cervical cancer research, and to discuss the importance of conveying an

understanding of these advances to the American public.

We are making real progress against cancer. We measure progress against cancer

in two ways: first, the increase in knowledge about cancer, and second, the reduction of the burden of this disease on people. We have made progress in both our

fundamental understanding of this disease and in our efforts to prevent and treat

it. This is already evident in the declining cancer incidence and death rates. Between 1990 and 1995, these rates dropped for all cancers combined and for most

of the top 10 cancer sites, reversing an almost 60-year trend of increasing cancer

cases and deaths in the United States.

After increasing 1.2 percent per year from 1973 to 1990, the incidence rate for

all cancers combined declined an average of nearly 1 percent per year between 1990

and 1995. The incidence rates declined for most age groups, for both men and

women, and for most racial and ethnic groups. The exceptions were black males,

where the incidence rates continued to increase, and Asian and Pacific Islander females, where the incidence rates were level. The overall death rate declined an average of 0.5 percent a year from 1990 to 1995, with the declines greater for men

than for women. The only racial and ethnic group not included in the decrease in

death rates was Asian and Pacific Islander females.

From 1950 to 1970, the incidence and mortality rates of invasive cervical cancer

fell impressively by more than 70 percent. From 1970 to 1995, these rates decreased

by more than 40 percent. Although cervical cancer has been steadily decreasing,

worldwide it is still the third most common cancer among women. About 400,000

new cases are diagnosed each year, predominantly among the economically disadvantaged, in both developing and industrialized nations. In 1999 an estimated

12,800 cases of invasive cervical cancer are expected to occur in the United States

and approximately 4,800 women will die. We must continue our research efforts to

determine the most effective ways to eliminate cervical cancer.

Recent Advances in Understanding Cancer

As we understand the nature of cancer, we understand that it is a complex set

of diseases, and that the answers to cancer are related to the most fundamental

mysteries of life itself. We know that cancer is not one disease, but at least 100 different diseases that share certain features. Because of this it is unlikely that one

magic bullet will solve the problem.
30

The most remarkable progress in the past 25 years has been in our knowledge

of cancer biology. We are dramatically extending our understanding of what is required to turn a normal cell into a cancer cell. Cancer arises when a single cell

changes so that it divides continuously, released from the controls that constrain the

replication of normal cells. This transformation results from changes in the function

and activity of genes. Of the approximately 100,000 genes found in the human genome, the altered activities of only a relatively small number of genes are responsible for transforming a normal, well-behaved cell into a cancer cell. Identifying

these cancer genes defines the central scientific hunt in cancer biology, and opens

an unprecedented window into the nature of cancer. Up until now, our detection

tools have lacked the sensitivity and the specificity that we must demand if early

detection is to be useful and successful. Our interventions, despite their success,

have, by and large, been the result of guesswork. But now, we are at a point where

we can transform our approach to cancer.

No one genetic alteration is enough to make a normal, healthy cell a cancer cell.

Rather, an accumulation of changes in a relatively small number of genes during

the lifetime of a cell is required. We have learned that some individuals carry a very

high lifetime risk of developing cancer. This understanding has allowed us to begin

describing the evolution of specific cancers from predisposition to precancer to cancer. Each cancer is ultimately defined by its particular pattern of altered and normal gene activity. This unique pattern determines the cancer’s rate of growth, tendency to spread, responsiveness to hormones and therapies, and also predicts the

ability of a persons immune system to recognize and respond to the cancer. Moreover, cataloging these molecular patterns will ultimately tell us how many different

cancers exist, and enable us to distinguish the differences between a cancer cell and

a normal cell.

We also are learning to understand the causes of cancer. Research on cancer

risk—the probability that the disease will occur in a given population—is identifying

populations with a significant probability of developing cancer. Because cancer is a

multistage process, analysis of risk factors leads to the development of prevention

and control strategies, as well as early detection methods, and in some cases more

precise treatments. Epidemiologic research has identified many factors that increase

cancer risk. Most of these are related to environment and lifestyle, while others are

part of a person’s genetic makeup. With the exception of a few genetic conditions,

however, it is still not possible to predict with any degree of certainty that a person

having one or more of these factors will develop cancer. This uncertainty is related

to the very nature of cancer and the need for many specific alterations to accumulate in a single cell for that normal cell to be transformed into a cancer cell.

Understanding Cervical Cancer

The etiology of cervical cancer is similar throughout the world. Cervical cancer results from a series of genetic changes. The National Cancer Institute is funding numerous studies to enhance our understanding of cervical cancer. Epidemiologic studies have demonstrated that infection with human papillomavirus (HPV) is the major

risk factor for development of preinvasive or invasive carcinoma of the cervix. The

virus contains oncogenes that can cause genetic changes or mutations in the cells,

but further changes are necessary for cancer to develop. In most women and men

with HPV infection, these other genetic changes do not occur and therefore, the individuals do not develop cancer or experience other adverse health effects besides

HPV infection. A large study in Costa Rica also aims to understand why common

HPV infections sometimes persist and progress to cervical cancer. Ethnicity-related

host factors such as immune status, genetic susceptibility markers, parity and nutrition are being studied intensively. Findings from this investigation are likely to be

relevant to minority populations in the United States since the incidence and mortality rates for cancer of the cervix are two to three times higher in Hispanic and

African American women compared to White women. Certain Asian American populations, especially Vietnamese women, also have high rates of cervical cancer. Ethnic differences exist mainly in women over 50 and are decreasing over time. Other

known cervical cancer risk factors include long intervals since last Pap test, multiple sexual partners, cigarette smoking and higher number of births.

Cervical Cancer Screening

The majority of cervical cancers develop through a series of gradual, well-defined

precancerous lesions. During this lengthy process, the abnormal tissue is easily detected by the Pap test. In the majority of women, the abnormalities will clear up

without treatment, but in some instances a few of these abnormal cells will develop

into cervical cancer. Early detection of the disease through the use of a Pap test

is directly related to survival. The five year relative survival rate for cervical cancer
31

is 88 percent for women with an early diagnosis of localized disease. For women initially diagnosed with later stage cervical cancer, the survival rate is only 13 percent.

Studies have found that the risk of developing invasive cervical cancer is 3-10 times

greater in women who have not been screened. Risk also increases with longer duration following the last normal Pap test.

Women ages 65 and older account for nearly 25 percent of cervical cancer cases

and 41 percent of cervical cancer deaths in the United States. A National Health

Interview Survey has shown that more than one-half of all women ages 65 and older

have not had a Pap test in the past three years. The pap test is the most effective

screening procedure for detecting abnormal changes in the cervix but many older

women do not know how often to get a Pap test, and are unlikely to be tested regularly. Since, many older women do not get regular pap tests, the older a woman is

when cervical cancer is diagnosed, the more likely she is to be diagnosed with later

stage disease.

NCI is conducting a large national study to find the best way to manage the mild

abnormalities that often show up on Pap tests. The study, called the ASCUS/LSIL

Triage Study or ALTS is comparing three approaches: 1) immediate colposcopic

exam and biopsy (the current standard); 2) repeating Pap test every six months (because most abnormalities return to normal without treatment); and 3) testing for

cancer-associated types of HPV as a means to differentiate between abnormalities

that need immediate colposcopy and those that can be best followed with repeat Pap

tests. The final results of this study are expected in three years and could affect

the 2 to 3 million American women each year who learn that their Pap test has

uncovered a mildly abnormal change in cells lining the cervix.

Advances in Therapy

Despite screening, women still get cervical cancer and need therapy. Forty years

ago, it was not clear that cancer, other than that which could be removed surgically,

could even theoretically be cured. The first proof that cancer can be treated and

cured came with childhood cancers, where survival was once measured in weeks to

months and where now the great majority of children with cancer are cured. Now,

for some cancers, our ability to cure is relatively predictable. For others, our ability

to cure is remarkably unpredictable.

Cancer research is also improving the traditional mainstays of treatment—surgery, radiation, and chemotherapy. Clinical trials are instrumental in these improvements. Last month in an important advance notice, NCI issued a Clinical Announcement to thousands of physicians who treat cancer, describing the results of

five large studies that have shown that women with invasive cervical cancer have

better rates of survival when they receive chemotherapy that includes the drug

cisplatin along with radiation therapy. Until last month, surgery or radiation alone

had been considered standard treatment for this form of cancer. The new findings

show that the risk of death from cervical cancer was decreased by 30 percent to 50

percent by combining cisplatin-based chemotherapy with radiation therapy in

women who require radiation therapy for treatment of cervical cancer. This new approach to cancer therapy is the direct result of the Nation’s clinical trials system.

Cervical Cancer Prevention

NCI is leading the development of a vaccine to prevent cervical cancer. This vaccine is based on the concept that almost all cervical cancers are caused by

papillomavirus infections. (HPV type 16 has been found in more than one-half of

cervical cancers, and three other types of HPV are found in another 30 percent of

the tumors.) The vaccine has proven highly effective in animal trials. The vaccine

is likely to be safe since it is not infectious and does not contain the potentially cancer causing viral genes. Among prevention vaccines in development, three early

phase trials are in progress and being tested in people. One of these, developed at

NCI in collaboration with the National Institute of Allergy and Infectious Diseases

(NIAID), the NIH Office of Research on Minority Health and Johns Hopkins University, has been tested in a phase I trial, and the preliminary results have been very

encouraging, showing that it stimulated production of HPV antibodies and was safe.

If these results are confirmed after further follow up and analysis, a full efficacy

trial will test the NCI vaccine in a larger group of women in the United States and

Costa Rica, leading to a full phase III trial in Costa Rica. Determining the long term

efficacy of this preventative vaccine will take several years. The NCI is also working

with investigators in universities and industry to develop vaccines which might improve cancer treatment.

NCI also conducts and supports research into behavioral aspects of cancer prevention. Smoking cessation is a major research priority at NCI since exposure to cigarette smoke is associated with increased rates of many cancers, including cervical.
32

Dietary intervention is another research priority for the institute since increased intake of certain micronutrients and other dietary factors such as carotenoids have

been suggested as being associated with a decreased risk for developing cervical cancer.

Public Understanding

Communicating with cancer patients, individuals at high risk for cancer, the general public, and the health care community is a central component of NCI’s mission

and mandate. Our programs are based upon needs identified through epidemiologic

studies and market research among specific population groups, resulting in programs that are relevant and understandable to each group. Our patient education

program, leadership initiatives for special populations, and minority research networks are all actively involved in spreading state-of-the-art information about cancer prevention, detection, diagnosis, treatment, and care.

The primary avenues NCI uses to communicate with the public and the health

care community are:

Clinical Announcements: Important cancer research findings are released directly

to the public and to the thousands of physicians who treat cancer patients through

NCI’s clinical announcements. Announcements of research findings are mailed directly to physicians and the national press is provided with the announcements so

that they can inform the public.

World Wide Web (http://www.nci.hih.gov): Currently NCI is redesigning its web

site to increase its usefulness as a communication tool. The new web site will be

organized so that clinicians, researchers, and the public can quickly and easily locate up-to-the-minute information that is relevant to their needs. A new addition

to NCI’s Web site is the Cancer Trials site (http://www.cancertrials.ncl.gov).

Through this site, patients, health care professionals, and the public can learn about

ongoing NCI-sponsored trials, read about the most recent advances in cancer therapy, and explore other information resources related to cancer treatment. This web

site was used by many patients and others who wanted information about treatment

advances publicized over the past several months.

Cancer Information Service (CIS): The CIS provides accurate, up to date cancer

information to patients and their families, the public, and health care professionals

in every state through 19 offices located at NCI-funded Cancer Centers and other

health care institutions. By dialing 1-800-4-CANCER, callers are automatically connected, free of charge, to the office serving their region. Information on specific cancer types, state-of-the-art care, clinical trials, and resources such as support groups

or screening and smoking cessation programs is provided in English or Spanish by

specialists who respond to more than 600,000 inquiries annually. The CIS regional

offices are NCI’s focal point for state and local cancer education efforts that target

underserved, high risk, and low literacy populations.

The CIS distributes informational resources on cervical cancer free of charge. In

order to reach the ethnic populations that are at increased risk for cervical cancer,

NCI is collaborating with the Food and Drug Administration in distributing Pap test

and cervical cancer brochures in Vietnamese, Cambodian, Samoan, Laotian, Thai,

Chinese, and Korean. The CIS also distributes an intertribal video on early detection of cervical cancer for American Indian Women that was produced in conjunction

with the Nebraska Department of Health.

Physician Data Query (PDQ): Patients and health care professionals want and

need access to accurate, up-to-date, comprehensive information about ongoing clinical trials. Through PDQ, NCI provides information about NCI-sponsored trials. We

are in the process of expanding the database, with the cooperation of patient advocates, the Food and Drug Administration, and the pharmaceutical industry, to include all cancer clinical trials approved by the FDA and to revamp the way information is presented. This system has served as a model for other institutes at the National Institutes of Health, and we want to ensure that it continues to be responsive

to the needs of the communities we serve.

Medical choices are increasingly made on an individual basis, requiring that physicians and their patients have access to the resources needed to make an informed

decision about their treatment and care. Communicating the importance of research

findings to physicians and patients in a clear and understandable manner is central

to making critical decisions about a patient’s treatment and care. NCI has launched

a new national media campaign on cervical cancer screening—‘‘Pap Tests: A Healthy

Habit for Life.’’ The first phase of the campaign is focused on encouraging women,

ages 65 and older, to get regular Pap tests since they continue to be at risk for cervical cancer although their screening rates decrease with age. The second phase of

the campaign targets health professionals, encouraging them to continue to screen
33

their older female patients because research has shown that general and family

practitioners are not likely to screen their older female patients.

NIH Consensus Statement on Cervical Cancer: The objective of this NIH Consensus Statement is to inform physicians and the general public of the results of

the 1996 NIH Consensus Development Conference on Cervical Cancer. Following established procedures, the consensus statement was prepared by a non-Federal, nonadvocate, 13 member panel representing the fields of obstetrics and gynecology,

gynecologic oncology, radiation oncology and epidemlolgy. The statement provides

state-of-the-art information regarding preventive approaches and appropriate management of cervical cancer and presents the conclusions and recommendations of the

consensus panel regarding these issues. In addition, the statement identifies those

areas of study that deserve further investigation such as: studies to assess qualityof-life issues in patients undergoing therapy for both preinvasive and invasive lesions of the cervix; research on the modification of high-risk behavior in young people to reduce the rate of HPV; research on ways to improve screening in populations

that are typically underscreened such as the elderly, ethnic minorities, and the poor;

and research on the development and testing of prophylactic and therapeutic vaccines against HPV.

We hope this overview provides you and the members of the committee a sense

of the importance of ongoing research on cervical cancer. Thank you for your interest in the cervical cancer research activities of the NCI. We would be pleased to answer any questions.

Mr. BILIRAKIS. Thank you very much, Dr. Lowey.

In the process of trying to prepare for these hearings, we always

ask that the testimony be submitted as much in advance as possible. The testimony came in from CDC, as I understand it, this

morning. I know that in your particular case, we gave you plenty

of notice for this hearing.

With all due respect, we would appreciate you help by submitting

testimony promptly in the future.

For years, when Florida’s late Governor, Lawton Chiles, was in

the Senate up here, we worked together. I was a co-chairman with

him on the subject of infant mortality. After discussions and research, we determined that there are adequate resources available

to help reduce the very high incidence of infant mortality in this

country. But, the problem was being able to get the mothers-to-be

to the resources. That was a big problem. We came up with mobile

sources. If we could not get them to come to us, we would go to

them.

If a person qualifies for Medicaid, the program covers the Pap

smear. Medicare, because of recent legislation I wrote with Mr.

Brown and others, covers it now. I believe most, if not all, private

insurance plans do. Now I know that there is a group of people who

don’t fall in those particular categories. What is the roadblock to

Pap smear screening? We have determined that the early detection

is so very critical. Can you address that, Dr. Valdiserri or Dr. Lee?

Ms. LEE. Yes, that is a very good question, and I think there are

many barriers. There has been a lot of research in this area.

Our program particularly is targeting those women that don’t

have any insurance, including Medicaid. Those women are from

that 40 million, and we, of course, only have funds to cover about

12 to 15 percent of that population.

The research indicates a lot of factors. It is real important that

physicians and other healthcare providers take the lead in encouraging women because many women take their cue from their physicians. It is real important for us to encourage all healthcare providers to add this to the many things they are supposed to be

doing.
34

We know that cervical cancer is highest in poor women, uninsured women, minority women, and women who are foreign-born,

and women who don’t receive regular healthcare.

Mr. BILIRAKIS. But, you are talking now of women who may not

be well informed about the nature of this threat.

Ms. LEE. Correct. Exactly. So there are many parts of CDC’s National Breast and Cervical Cancer Early Detection Program that

we are trying to come in and figure out how to get those women—

that is what I talked about in my testimony. That is our hard job,

to get the women who nobody else can seem to get. We can pay for

it, but we would have to find them.

We have given money to many primarily community-based organizations throughout the country, to farm worker organizations,

migrant health, to organizations that provide services to Asian immigrants, to Hispanic and Latin American immigrants, to organizations targeting Hispanic, elderly and the elderly in the Black community. We go through churches. We go through community clinics. We have programs that fund lay health educators, and actual

women who themselves have had cancer, but are not otherwise

trained in the health profession to go out and witness to women

about what they need to do. So, there are many strategies that we

are working on identifying.

We actually have a whole set of grants now. I will conclude my

answer with this: a bunch of grants to these community-based organizations take proven strategies that have been proven through

good evaluation research and disseminate them into the community or different communities around the country. These are the efforts that we are trying to do to reach these women that nobody

else can seem to reach.

Mr. BILIRAKIS. College women would not generally fall within the

category that you described. Yet, I understand that last year the

New England Journal of Medicine released a study that tracked

college women at Rutgers University over a 3-year period of time

and found a high incidence of HPV. So, what is the explanation,

when they don’t fall within that category?

Mr. VALDISERRI. Two comments on that particular study: I think

that it reinforces what I said earlier in my testimony about probably as many as 50 percent of all sexually active adults in America

are infected with HPV. I think that, to follow up on Dr. Lee’s comments, this is an important issue that is not, unfortunately, unique

to screening for cervical cancer. In fact, I remember a very interesting approach to this, looking at barriers to prenatal care, where

a researcher actually went through and characterized a whole set

of attitudinal barriers, informational barriers, provider barriers,

system barriers, et cetera. So, to follow up on what Dr. Lee was

saying, I think that there are a number of reasons why; there is

no single reason why this is happening. Part of the complexity of

the program and the need to do operational research is to understand what a particular barrier might be for a community of

women and then to disseminate model practices to try to address

that.

Mr. COBURN. Would the chairman yield for just a second a follow-up question?

Mr. BILIRAKIS. The chairman does not have much time, but go

ahead.
35

Mr. COBURN. Your testimony that 50 percent of sexually active

adults are carrying this, but, if you exclude monogamous relationships, if you include that, what you are really saying is that it is

a much higher percentage in the population that is outside of the

married monogamous relationships. So, that’s the populations that

you are studying. So, the real prevalence is much higher than 50

percent in terms of the sexually active non-monogamous relationships. Is that correct?

Mr. VALDISERRI. Well, let me, first of all, say that I don’t believe

that I stated that 50 percent were carrying it, because I think several of my colleagues indicated that in many instances this infection is transient. We don’t know a lot about the natural history, but

I think that there is a belief that in some people the infection

clears, or at least it is no longer detectable.

What I did say was there are estimates that at least as many

as 50 percent may have been infected by HPV. Part of the difficulty, Dr. Coburn, is that we do not have a lot of good surveillance information nor incidence information about this. I think that

it is fair to say, as I mentioned, that the number of sexual partners

is a clear-cut risk factor for becoming infected with HPV. So that

the greater the number of sex partners, the more likely an individual would be exposed to HPV.

Mr. COBURN. Well, I thank the gentleman.

Mr. BILIRAKIS. Mr. Brown.

Mr. BROWN. Thank you.

Dr. Lee, you talked about the higher rate of cervical cancer

among foreign-born women, and my understanding is that AsianIndians, in particular, have a higher incidence, and we have talked

about low-income people having high incidence. Explain why that

is in all of those groups.

Ms. LEE. Maybe can I speculate some? Will you allow me?

Actually, the highest rate in recognized racial and minority

groups in the country is among Vietnamese women. Alaskan Natives, Hispanics, Korean women, all have very high rates. I think

a whole lot of this has to do with being recently arrived in this

country perhaps from—obviously, not from Alaskan Natives, but

for the Asian women and for Hispanic women from Latin and

Central——

Mr. BROWN. Is it all Asian women or especially—not Indian, but

especially Korean and Vietnamese?

Ms. LEE. It is mainly Southeast Asian and Vietnamese. I think

Japanese women actually have a very low rate.

Mr. BROWN. And Indian women?

Ms. LEE. I have not seen the rates broken out by Indian.

Mr. BROWN. Asian-Indians, I am sorry.

Mr. LOWEY. Native American Indians.

Ms. LEE. From the subcontinent.

Mr. LOWEY. In India there is a very high incidence.

Ms. LEE. The statistics we have in this country on Asian women

don’t break out the Asian-Indian women.

I think that what we have found in this country is that the most

profound predictor of getting cervical cancer in this country is not

having screening. Okay, that does not really count in South America, for example.
36

Mr. BROWN. Does that account entirely for the high incidence

among low-income people?

Ms. LEE. I would say in this country it is a very important thing.

I am not talking about the pre-cancerous lesions because, if you are

screened adequately, you are then diagnosed with pre-cancer and

that is cured. The pre-cancerous lesions are also caused by HPV

and the other known risk factors.

I think the primary reason that you find high rates, not the only

but the primary reason, in these foreign-born and Hispanic and

Asian subgroups is because they have recently arrived in this country and came from a place where they were not being screened regularly, or they are in a culture in this country where they are not

getting screened regularly. That is, I think, the reason that we see

the high rates in those subpopulations in this country.

Mr. BROWN. Talk more about the incidence in low-income

women, please.

Ms. LEE. Now I was talking about the incidence in various racial

and ethnic minority groups.

Mr. BROWN. No, I am asking you to discuss why the incidence

is higher among low-income women.

Ms. LEE. I think it is among the same reasons that those women

of low-income predominantly are overrepresented members in the

minority community. When we look at screening data from national

survey data, we are less likely to see women of low-income and

low-educational status having regular Pap screening.

Mr. COBURN. [presiding] Thank you, and I will recognize myself,

if I may.

First thing I would like to do is submit for the record a study

that was recently published in Pediatrics about the incidence of

early dysplasia and carcinoma in situ in teenagers 10 to 19, published March 3, 1999 in New England, and a ratio of 4 percent of

advanced dysplasia among that group. If I have no objection, I

would like to enter that into the record.

[The information referred to follows:]
37
38
39
40
41
42
43
44
45

Mr. COBURN. I want to spend just a few minutes going through

this. Dr. Valdiserri, you have stated that there are 45 million people perhaps that have been exposed to this virus or this combination of viruses. We know that it accounts for somewhere above 90

percent of invasive cervical cancer. We have not talked about the

tremendous outbreak and tremendous epidemic increase in cervical

dysplasia in this country that we are seeing. Would you care to

comment on that?

Mr. VALDISERRI. I don’t know that I am the best person to comment on that particular aspect of it. From my focus at CDC, in my

center we are not doing surveillance on cervical dysplasia. In fact,

we have a meeting scheduled in early April with the American

Cancer Society and colleagues from NIH and other colleagues at

CDC to consider a whole host of issues around HPV, and surveillance will be one of the considerations. But I think that when we

are talking about surveillance in that context, we are talking primarily about HPV surveillance.

Mr. COBURN. That leads me back to my next question.

You said in your verbal statement—and I have read your written

statement—that we have data that says perhaps this may be a

short-lived infection. Would you care to submit for this committee

all the scientific data that you say are the studies, the peer-reviewed studies, that are out there that would say that this is shortlived, and that we can actually have for us to look at the experience model that you are calling on, to give us that information?

Mr. VALDISERRI. Let me state for the record, Dr. Coburn, that I

am here as a representative of the National Center for HIV, STD,

and TB Prevention. My particular expertise is not in human

papillomavirus. I don’t know if that was a rhetorical question.

Mr. COBURN. No, it really was not.

Mr. VALDISERRI. But, through my reading and through my discussions with some of the experts that we have at CDC, let me say,

first of all, there is much that we don’t know about the natural history of HPV. There are many, many issues——

Mr. COBURN. Right, but let me interrupt you there because that

is exactly where I am going. My whole point is this is the largest

sexually transmitted disease that we have in the country. It affects

more people. It accounts for 90 percent of the cervical cancer. My

question to you is, why is not a reportable disease?

Mr. VALDISERRI. Let me answer that one. But, let me go back to

your first question about why I mentioned that some experts indicate that this might be short-lived. I think that that is a reflection

of the fact that there is good evidence to show, although there is

not incidence data, there are many, many studies showing the

widespread prevalence of HPV, and this is linked with the fact that

clinically, as my colleague from NCI stated as well, fortunately, for

most men and women who are infected, this is a benign condition

that does not even result in any kind of symptomatic presentation.

So, I think to go back to your first question, that is why some

of the experts in the field, they don’t know for certain, but think

that this may be a short-lived condition.

Your second question, I am sorry now, I have forgotten it.

Mr. COBURN. Why is it not a reportable disease?
46

Mr. VALDISERRI. Why is it not reportable? There are two ways to

answer that. I guess the more direct is that, as you well know, reportable diseases are determined by States.

Mr. COBURN. As I know, the CDC has a list of 53, I believe, that

mandate to the States to report them of which some of their funding is dependent upon whether or not they report.

Mr. VALDISERRI. That’s not my understanding of the way it

works out in terms of the Federal and State relations.

Mr. COBURN. Then let me rephrase the question. Why is the CDC

not making a recommendation that this be a reportable disease?

Mr. VALDISERRI. That is what I thought you might be driving at.

Let me say, first of all, at CDC we would like to go on record saying that we would clearly like to have additional surveillance information about HPV, for a number of reasons.

Mr. COBURN. I am going to interrupt just for a minute. Here is

the No. 1 cause of cervical cancer in the country. Five thousand

women, at least, a year are dying from it. It is a known etiologic

agent. It can be identified. It can be prevented with screening. Why

would we not want the Center for Disease Control to make a recommendation that this is a reportable disease? Answer that from

a logical conclusion.

Mr. VALDISERRI. Well, I think there are a number of reasons why

there would be difficulties, in that if a State determined that it

wanted to make a law reporting HPV, first of all, what test would

we use? Would people use abnormal Pap smears as what constitutes the reporting condition? Given that most instances of HPV

infection, as you well know, are asymptomatic and don’t result in

any kind of——

Mr. COBURN. Dr. Valdiserri, my point is that every day when I

am in my practice, I am telling a women she has a cervical dysplasia and I am explaining to her how she got that. She got it because somebody gave her human papillomavirus. And, if I don’t follow my obligation as a physician to say you have a disease that is

transmissible—it is 300 times more transmissible than HIV.

Now, to tell me that I should not make that a reportable disease,

that she should not inform her partners—we recently had the

American College of Pediatricians come out and say we should not

circumcise young men, but they totally ignored human

papillomavirus and the disease characteristics that we are getting

ready to see with cancer of the penis.

Mr. VALDISERRI. First of all, we don’t tell individuals who are infected with HPV and have clinical manifestations and know that

they are infected that they should not inform their partners. That

is a misperception.

Mr. COBURN. No, I did not say that.

Mr. VALDISERRI. Well, I want to go on record saying that.

Mr. COBURN. But, if it is a reportable disease, then it becomes

an obligation on the part of the physician to do what we all

know——

Mr. VALDISERRI. If he or she can report it. What I am trying to

get in the record is that there are some difficulties with the one

family of tests that are available. My understanding is that they

don’t identify all the viral subtypes.

Mr. COBURN. Absolutely not; they don’t. You are right.
47

Mr. VALDISERRI. That is correct, and we also went on record saying that there are a lot of questions about, what does antibody

mean? Do people have antibody or not?

Mr. COBURN. We will spar back and forth here for a minute, but

we also know that they DNA probes for chlamydia and gonorrhea

are not 100 percent accurate either, but we still report those diseases.

Mr. VALDISERRI. Not in every State.

Mr. COBURN. Well, in most States they are reportable diseases.

I will yield back my time and then I will ask for additional time

when we finish. The gentlelady from California.

Mrs. CAPPS. I want to go back a little, although this part of what

I want to say is not really a question, because I found the original

discussion, after you made your testimonies and throughout your

testimonies, to be so much about basic healthcare and health education. And, as a school nurse, it just resonates with me my bias

about cervical cancer, so highly treatable, so easily preventable,

with all these questions about why aren’t women who are poor,

who are born in other countries, and then we are talking about all

the barriers to access, and it comes right back to people who should

be talking. We should be talking about this with our well-child clinic care providers, pediatricians, and those who work with young

families, because the next generation starts in utero, as was mentioned, in terms of the risk factors, but, also, for the education that

must go on until we get a climate of being comfortable seeking

help, particularly, when it comes to sexually transmitted diseases.

And, we have a lot of discussing to do about how we can get to that

point in terms of healthcare—such preventive healthcare, family

oriented, really supporting families at a critical time and young

people, and that is why I am delighted that we are having this

hearing.

I hope that we can continue that conversation, and that whatever

we can do here on the Hill to help get some of those barriers eliminated in our communities—and I am intrigued by the models that

you are using. I would like to find ways to lift those out, and the

ones that work, we should be doing everywhere because they are

not costly. I know that it is mostly working neighborhood to neighborhood using peers and survivors, or whatever, the ways that you

have found to work.

Mr. VALDISERRI. May I make just a statement? I think that is

such an important point, because when we think about an infectious disease process or an infectious disease-related cancer like we

are talking about here, we obviously focus on the basic research,

which is fundamentally important. But, there are a whole host of

operational and health services research questions like the ones

that you have alluded to and like to ones that Dr. Lee mentioned

that I think are extremely important that have to take place, sometimes even after some of the basic research questions have been

answered. So, I appreciate your bringing that point up.

Mrs. CAPPS. Then, just one final note on that: You are coming

here to the House of Representatives. Each of us has local constituencies that we represent of interest to you all, and what you do,

the health of our communities depends on getting this information
48

out. So, that is how I would like to see this conversation move forward.

What are some of the ways we can help you get the word out,

try new models, and also, what can we bring to you from our communities in terms of either barriers or models for achieving success

in this area?

I think what we have in the situation with cancer of the cervix

is such an example. It is like a symbol of the good—it is treatable.

There is a low-cost screening technique that is widely available,

and yet, why are so few women taking advantage of the opportunity? So, that’s to be discussed.

One quick one for me: A couple of you alluded to smoking and

the relationship and I am curious. Just a couple of words about

why.

Mr. TRIMBLE. Smoking appears to increase the risk of a number

of epithelial of skin cancers. So we all are now aware of the association between smoking and lung cancer. But, it also increases the

risk of cancer of the head and neck, cancer of the esophagus, cancer

of the vulva, cancer of the vagina, cancer of the cervix.

Mrs. CAPPS. Is there a particular way that this is easily explained to the lay public?

Mr. TRIMBLE. No.

Mrs. CAPPS. No. The linkage?

Mr. TRIMBLE. Well, we don’t fully understand the mechanism by

which cigarette smoking does increase these risks. We note,

though, that cotinine, which is one of the byproducts of nicotine, is

found expressed in the cervical mucus after a person smoked a cigarette, but we don’t know the specific mechanism for each of the

cancers.

Mrs. CAPPS. I think we need to disseminate that information as

well.

Mr. VALDISERRI. And, I mentioned smoking as an epidemiologic

factor in HPV infection, but that has not been as consistent a finding as smoking in cervical cancer.

Mrs. CAPPS. Thank you very much. Thank you for being here

today.

Yield back the balance of my time.

Mr. COBURN. Thank you, and the gentleman from Pennsylvania

is recognized.

Mr. GREENWOOD. Thank you, Mr. Chairman.

I want to do what Senator Mack did and take off all my hats,

except leave my daddy hat on. My little girls are just about to be

12, Katie is, and Laura is 131⁄2. They are not sexually active. They

will be someday. I have encouraged them to wait until after menopause, but I don’t think that I am going to succeed there.

Mr. COBURN. If the gentleman would yield, there is a study that

shows the incidence of cervical cancer in nuns is zero.

Mr. GREENWOOD. Nuns. Cervical cancer is zero among nuns.

That is another option for them that I will encourage.

But, realistically, what we just heard about these rates of 43 percent among college coeds, I can assume that if one of my daughters

is off at a college campus and becomes sexually active, that there

is an extraordinarily high likelihood, particularly if she had more

than one partner, if half the guys out there have HPV, and she
49

would have two partners over the course of 4 years of college, virtually 100 percent likelihood that she gets a disease that is a very

strong precursor to a very deadly cancer.

I would be happy to be corrected if my assumptions there need

to be corrected. But, I think, whether they do or not, the fact is

that young people today, being sexually active, as the huge percentage are, are enormously at-risk for disease that is enormously

deadly.

I would guess that if you went to any college campus, go to the

best Ivy League campus in the country and ask male and female

college students about HPV; I would guess that an extraordinarily

small percentage of them have ever heard of it, know what it

means, know how common it is among their fellow students and

their potential sexual partners—let alone have knowledge of the

fact that it is essentially incurable, and let alone that it is a precursor to cancer which is fatal.

I have two questions: One, is there any other disease out there

that is as widespread, as incurable, and is potentially devastating

as this one? That is my first question. My second question is: Two,

what are you doing to inform the American public, particularly the

young sexually active Americans, that every time they get in bed

with somebody it is a loaded gun?

Mr. VALDISERRI. Let me start out, and I suspect that my colleagues will want to comment as well.

First of all, in answering your first question, I guess I would ask

you to remember, although we are dealing with an extremely serious situation here, that most instances of HPV infection are benign

and don’t result in cervical cancer. I am not trying minimize——

Mr. COBURN. If the gentleman would yield, I would like for you

to submit to the committee the scientific peer review data that says

that, because I can’t find a whole lot of it.

Mr. VALDISERRI. Yes, that is not a problem. There is also a very

good summary in the new STD text that came out that has hundreds of references that tell what we know about natural history.

So, we can do that.

Mr. GREENWOOD. Just since I am not a physician in this triangle

here, when you say most cases are benign, tell me what you mean

by that.

Mr. VALDISERRI. What I mean is that, based on the evidence that

we’ve accumulated, there are specific subtypes, specific types of the

virus that are associated with cancer and specific types of the virus

that are not, and maybe my colleagues from NIH and NCI can

speak to this, but, epidemiologically, the estimates that I have seen

are that about 5 to 10 percent perhaps of women who are infected

with the so-called high-risk or the cancer-associated viruses will go

on to develop cervical cancer if there is not the screening that detects the pre-cancerous lesions.

Again, that is not to minimize that percentage, because it is a

tragedy each and every time it happens. But, it is important to

keep that in mind when you think about how widespread this viral

infection is in the population.

I think your second point is perhaps a little easier to talk to. You

may be aware of the fact that the Institute of Medicine published

a report on sexually transmissible diseases in America, I guess it
50

has been about 2 years ago now, and they called it ‘‘The Hidden

Epidemic.’’ They talked about this whole issue of all of the sexually

transmissible diseases that confront sexually active individuals,

and I would just like to go on record saying that you are absolutely

right; that we do have to get this information out there and it is

one of the reasons it is important to stress to individuals that there

are a lot of health benefits that derive from delaying sexual activity. But we also know that sooner or later people will become sexually active, and then we have to also provide, to the best of our

knowledge, information about prevention in that context as well.

Mr. GREENWOOD. The one part of the question that I did not get

a response to yet was: Is there any other disease that is this prevalent? For 50 percent of at least a subset of the population that is

sexually active, for that population to have a particular virus, I

can’t——

Mr. VALDISERRI. Off the top of my head, I don’t know, and I

think it reflects the fact that the target organ for HPV is skin, an

epidermal surface, and that’s a pretty big target organ; there are

a lot of types of them.

Ms. LEE. Let me say that once infected is not the same as having

the disease; Okay? So, like, I had the flu last year, and if you went

back and you were able to check those antibodies, I would have it,

but that does not mean I am now affected by it. Let me just say

that let’s look at the positive of this. Unlike most cancers, we have

a test that works, and we have dropped the rate of cervical cancer

by 70 percent in the last 50 years. And so, most women who are

infected with the bad kind of HPV virus, and, in fact, go on to develop these neoplastic or pre-cancerous changes, can be, and are,

detected before they ever get cancer, treated in the physician’s office as an outpatient. Dr. Coburn can do it. They never have to do

the hospital. They don’t have to get a hysterectomy. They can still

have children, and then they go on. So, we can put a good, positive

spin on this for this kind of cancer.

Mr. GREENWOOD. We shouldn’t put any spin on it at all, but my

time is out.

Mr. COBURN. Next, I’d like to recognize the gentlelady from California.

Before I do that, I would like unanimous consent to put into the

record a letter from Dr. Clausner, from NIH Public Health Service,

dated February 19, to the chairman, in relationship to questions

that were asked by the committee—I believe you all had a copy of

this letter—and also a study published in the New England Journal of Medicine on the natural history of cervical—I will make sure

that you have it—cervical vaginal papilloma virus infection in

young women.

[The information referred to follows:]
51

DEPARTMENT OF HEALTH & HUMAN SERVICES

PUBLIC HEALTH SERVICE

NATIONAL INSTITUTES OF HEALTH

NATIONAL CANCER INSTITUTE

BETHESDA, MARYLAND

February 19, 1999

The Honorable TOM BLILEY, JR.

House of Representatives

Washington, D.C. 20515

DEAR MR. BLILEY: I am responding to your letter of January 12, 1999, in which

you pose fifteen questions about the possible relationship of induced abortion to

breast cancer, the relationship between human papillomavirus (HPV) and cervical

cancer, and the National Cancer Institute’s (NCI) dissemination of research findings

on these topics. I regret that I could not meet your request to provide a response

by January 29, 1999. My staff have worked closely with Mr. Marc Wheat to keep

him informed of our progress.

As requested, the questions have been restated below. The answer follows each

numbered question.

1. At the July 20 hearing on ‘‘The State of Cancer Research,’’ the National

Cancer Institute testimony addressed the importance of epidemiologic research in identifying the factors that increase cancer risk. How much of

the NCI budget is allocated to the funding of intramural and extramural

epidemiologic studies done for that purpose?

NCI funds the bulk of this research through the Division of Cancer Epidemiology

and Genetics (an estimated $60 million for intramural epidemiologic studies) and

the Division of Cancer Control and Population Sciences (an estimated $147 million

for extramural researchers). Additional funding from other NCI Divisions may be

relevant, but we included only projects that are directly related to studying factors

that increase cancer risk.

2. NCI has a long-standing focus on ‘‘preventable causes.’’ Are there preventable causes for breast cancer that have been identified by NCI? What

preventable causes have been identified for cervical cancer?

After discussion with Mr. Mark Wheat of your staff, ‘‘preventable’’ (for the purpose of this inquiry) exposures are those created by human intervention; i.e., herbicides, diet. In contrast, ‘‘unavoidable’’ exposures are those that occur in nature; i.e.,

genetics.

Breast Cancer

The leading known risk factors for breast cancer are largely unavoidable. Age is

the leading risk factor, with incidence rates increasing dramatically after age 50.

Family history is a strong risk factor, particularly if a woman’s mother or sister has

the disease. Genetic factors play an important role. About 50 percent of women with

a mutation in the BRCA-1 gene will develop breast cancer by age 70. It is important

to keep in mind that only between 5 and 10 percent of all breast cancers appear

to be attributable to an inherited genetic mutation. Some benign breast diseases increase risk, and a previous diagnosis of breast, ovarian or endometrial cancer is associated with risk.

Reproductive events are a strong determinant of subsequent breast cancer risk.

Early menarche and late menopause increase risk, while removal of both ovaries before menopause reduces risk. Having additional births after the first is associated

with a slightly reduced risk. The most consistent reproductive factor is the woman’s

age at first full-term pregnancy. Women without children and women having their

first child after age 30 have a two- to three-fold increased risk of this disease, compared with women who give birth before age 20. A woman with an interrupted first

pregnancy, either spontaneously or through induced abortion, does not reap the protective benefit of a full-term pregnancy.

Other risk factors may be considered ‘‘preventable.’’ Taking oral contraceptives

may increase risk for breast cancer at an early age (before age 45), and estrogen

replacement therapy may slightly increase risk of breast cancer. Among postmenopausal women, risk increases with weight, body mass, and distribution of

weight. The association with dietary fat consumption is inconclusive, while recent

studies have shown a fairly consistent though small effect of alcohol consumption

on breast cancer risk. Exposure to high doses of radiation increases risk, although

the effects of low-dose radiation are considered minimal.

Most of these ‘‘established’’ risk factors for breast cancer are associated with only

a moderately increased risk, suggesting that multiple factors may play a role in
52

each woman’s disease, and that unrecognized factors may exist. Further research is

necessary, is ongoing, and remains a high priority for the NCI.

Cervical Cancer

Sexual behavior has been identified as the major risk factor for cervical cancer.

Risk is increased by early age at first intercourse or numerous life-time sexual part- ners. The greater the number of sexual partners, the greater the risk of sexually

transmitted disease, which can be a risk factor. Abundant laboratory and clinical

data support a role for human papillomavirus (HPV) in cervical cancer. Cigarette

smoking is associated with increased risk. Barrier methods of contraception reduce

risk, and the use of oral contraceptives increases risk. Giving birth multiple times

is an independent risk factor, and vitamin C, beta carotene, or folacin (one of the

B complex vitamins) deficiencies may increase risk.

3. The NIH written testimony for the July 20 hearing states that ‘‘communicating with...individuals at high risk for cancer, the general public, and

the health care community is a central component of NCI’s mission and

mandate.’’ To that end, NCI has identified preventable target exposures of

cancer-causing agents as a key element in the prevention of cancer. What

work has NCI done to coordinate a Federal response to the prevention of

breast and cervical cancer? Specifically, what work has NCI done with the

Department of Health and Human Services Office of Population Affairs and

the HHS Health Resources and Services Administration to alert women to

avoidable exposure to carcinogenic agents? Who are the liaisons within

NCI, HRSA, and the Office of Population Affairs? Has NCI coordinated activity with the Title V and Title XX programs within those agencies.?

Federal agencies are designated to serve the United States in specific ways. The

National Institutes of Health (NIH), of which NCI is a part, is a research agency.

In its mission to protect and improve human health, the NIH (and NCI) conducts

and supports basic, applied, and clinical and health services research to understand

the processes underlying human health and to acquire new knowledge to help prevent, diagnose, and treat human diseases and disabilities. This may include developing an information campaign (such as the 5 A Day Program described below,

which was based on scientific evidence that increasing consumption of fruits and

vegetables reduces cancer risk) and evaluating its effectiveness at achieving its goal

(increasing the daily intake of fruits and vegetables). NCI also has a mandate to

disseminate research findings so that when the development and evaluation are

completed, other Federal and state agencies, and private sector organizations, may

take this information and apply it accordingly. NCI, therefore, plays an integral role

in these activities. For example, the Steering Committee for the National Action

Plan on Breast Cancer (NAPBC) includes NCI staff as members and working group

chairpersons serving this unique public/private trans-Federal partnership.

The NCI disseminates research findings widely through scientific publications,

press conferences, press statements, clinical alerts, patient education materials,

meetings of professional societies, television and radio, the World Wide Web, our

toll-free Cancer Information Service, our PDQ databases, and the Information Associates Program. Our staff has many contacts within agencies for a variety of programs and issues. Through these personal contacts, and those mechanisms mentioned above, Federal agencies and offices have direct access to information pertinent to their programs. In addition, we maintain and foster close working relationships with other Institutes that have formal collaborative relationships with the Office of Population Affairs—our projects and programs are thus included in that

broad knowledge base. NCI has several partnerships with other federal agencies

and non-federal groups to enhance our information dissemination activities.

NCI has not formally collaborated specifically on Title V (Substance Abuse and

Mental Health Services Administration) or Title XX (Adolescent Family Life Demonstration Projects) programs. As a research agency, NCI’s role is to conduct and

support research, then disseminate widely new knowledge gained. Following are examples of specific information campaigns:

• Mammography Screening—Scientific evidence supports NCI’s recommendation

that lives can be saved if women in their forties or older have regular screening

mammograms, every one to two years. Because this constituted a major change

in the level of scientific evidence to support screening mammography, it was imperative that NCI disseminate this information widely. Specific information targeting various populations and constituencies was developed and disseminated

using a variety of mechanisms, such as patient-oriented publications, education

materials, public service announcements, and electronic media.

• 5 A Day—Because fruit and vegetable intake has been clearly demonstrated to

provide a health benefit beyond cancer prevention, increasing American con-
53

sumption has tremendous potential to improve our Nation’s health. Because

health messages can be confusing, NCI set aside special funds for grantees to

find innovative ways to inform the public. In an unprecedented public/private

partnership, grantees and health departments nationwide participated in a

study of new methods to reach the public and influence behavior. These grants

are completed, and NCI and the Centers for Disease Control and Prevention

(CDC) are evaluating their success. If indeed Americans increased their consumption, then other public and private groups will have scientifically proven

methods to bring into their communities. • ‘‘Risk Disk’’—The Breast Cancer Risk Assessment Tool is a computer program

that women and their health care providers can use to estimate a woman’s risk

of developing breast cancer for two time periods—over the next five years and

for her lifetime—based on several recognized risk factors (see Question 2 for a

discussion of some of those risk factors). The tool compares these risks (given

as a percentage) to those of a woman of the same age with no risk factors other

than her age, and with the risk of women who were eligible to participate in

the breast cancer prevention trial using tamoxifen.

4. The July 20 NCI written testimony states that ‘‘NCI is actively pursuing development of a vaccine to prevent cervical cancer... based on the

concept that almost all cervical cancers are caused, at least in part, by papilloma virus infections.’ What is the status of the development of a vaccine

for this disease? How long will it be before a vaccine enters clinical trials?

Have any private sector entities partnered with NCI in the development of

this vaccine?

The vaccine is currently being developed in clinical trials. The Phase I study to

determine if the vaccine can prevent infection is underway at Johns Hopkins University, and preliminary results based on laboratory tests are encouraging—with no

toxicities yet reported. Following completion of the Phase I trial, a Phase II trial

to determine correct dosage is expected to begin in January 2000. A planned Phase

III randomized clinical trial involving 10,000 women to test the efficacy of preventing HPV (Type 16) infection is expected to begin in about 2.5 years. As in many

of our drug studies, we have partnered with a company to manufacture the viruslike particle contained within the vaccine. The manufacturer will have no role in

the evaluation of its benefit or safety.

5. Earlier this year, the New England Journal of Medicine published the

results of a study on human papillomavirus (HPV). Among sexually active

female students at Rutgers University, approximately 60 percent tested

positive for HPV at some time during the three-year study period. Given

that HPV is an agent of most cervical cancer cases, which kill nearly as

many women each year as AIDS, what does a 60 percent infection rate suggest to NCI about the long-term consequences of this virus? Does this infection rate suggest that condom usage is less effective at preventing HPV infection than it is in preventing pregnancy? Has NCI sponsored any research as to the effectiveness of condoms to prevent the transmission of

HPV?

Experts estimate that as many as 24 million Americans are infected with HPV,

and the frequency of infection and disease appears to be increasing. For most

women, HPV does not remain in the body. After initial infection, most women’s immune system can clear the virus within 18 months. Therefore, a high prevalence

at a point in time is not indicative of the numbers of women who will suffer health

consequences. In fact, most women suffer no serious health problems as a result of

HPV infection, nor do they know they have been infected. Although most HPV infections do not progress to cancer, it is important for women to have regular Pap

smears. Potentially precancerous cervical disease is readily treatable. By identifying

women with persistent infection through screening, and then treating those with

precancerous conditions (by removing the precancerous cervical tissue affected), we

relieve most of the burden of cervical cancer from HPV infection in the United

States.

Condoms are ineffective against HPV because the virus is prevalent not only in

mucosal tissue (genitalia) but also on dry skin of the surrounding abdomen and

groin, and it can migrate from those areas into the vagina and the cervix. Additional

research efforts by NCI on the effectiveness of condoms in preventing HPV transmission are not warranted. However, condom use is extremely important for preventing the transmission of other sexually transmitted diseases, and in the prevention of pregnancy. We include the use of condoms as an option in clinical trials if

methods of birth control or disease prevention are needed.

6. What is the amount of research dollars expended on HPV as compared

to the virus that causes AIDS? What is the ratio between the two research
54

budgets as compared to the number of women who die of the respective viruses?

There are over 80 types of HPV, about 15 of which are associated with cancer of

the cervix. NCI estimates that it will spend about $38 million on cervical cancerrelated HPV research, and about $235 million on AIDS-related cancers, in FY 1999.

There are about 5,000 deaths in the U.S. from cervical cancer each year, and more

than 200,000 deaths world wide. Over 90 percent of these cancers are HPV-related.

There were about 4,600 female deaths in the U.S., and 900,000 worldwide, from

HIV-related illness in FY 1997.

7. What action does NCI recommend be undertaken by the Federal government to address the public health threats of HPV?

Human papillomavirus (HPV) is one of the most common causes of sexually transmitted disease in the world. The NCI believes that if all women had pelvic exams

and Pap tests regularly, most precancerous conditions would be detected and treated

before cancer develops. At present, early detection and treatment of precancerous

tissue remain the most effective ways of preventing cervical cancer. This is communicated in our publications and public information. NCI is working to develop a vaccine that will prevent the main cancer-causing types of HPV, and is investigating

the use of HPV testing, via more accurate Pap testing programs, to improve cervical

cancer screening and prevention.

8. According to an Associated Press report on a Supreme Court ruling

dated January, 11, 1999, HHS had a hand in the removal of controversial

posters in the Philadelphia public transit authority that linked abortion to

breast cancer. According to this report, in ‘‘Early February [1996], the authority received a copy of a letter a federal health official had sent to the

Washington Metropolitan Area Transit Authority. Dr. Philip Lee, Assistant

Secretary of Health in the Department of Health and Human Services,

called the anti-abortion ad ‘unfortunately misleading’ and ‘unduly alarming,’ and said it ‘does not accurately reflect the weight of the scientific literature.’ Based on Lee’s letter, SEPTA removed the posters on Feb. 16,

1996.’’ Please provide the Committee with a copy of this letter, and copies

of all other letters HHS has sent since 1993 raising concerns about ads

making cancer claims that may be ‘‘unduly alarming.’’ On what basis was

the ad found to be ‘‘unfortunately misleading,’’ ‘‘unduly alarming,’’ and that

it ‘‘does not accurately reflect the weight of the scientific literature’’?

In early 1996, NCI staff drafted a response to requests for information about the

scientific evidence concerning the relationship between induced abortion and breast

cancer risk. The letter was drafted for Dr. Klausner’s signature (Attachment 1),

but there are no copies of other drafts, or of correspondence to SEPTA, signed by

either Dr. Klausner or Dr. Lee in NCI’s central files system or with queried staff.

There were several meetings with Dr. Lee and/or members of his staff to discuss

a response. We have suggested to Mr. Wheat that he ask the Department of Health

and Human Services, too, to search for relevant documents. NCI did issue a press

statement (Attachment 2) on February 14, 1996, regarding the SEPTA campaign’s

representation of information from the scientific literature. A search of NCI’s central

files, and among files of queried NCI staff, revealed no correspondence since 1993

concerning other advertisements making other cancer claims.

9. In a line of questioning at the July 20 hearing before the Health and

Environment Subcommittee, the NCI witness was asked about a very substantial body of research linking cancer to what is clearly an eminently

avoidable exposure which you did not mention in your written testimony.

Fully 25 out of 31 epidemiologic studies worldwide and 11 out of 12 studies

in the United States (many of which, I am told, were conducted or funded

by the NCI) show that women who elect to have even one induced abortion

show an elevated risk of subsequent breast cancer. What studies has NCI

conducted or funded related to the link between abortion and breast cancer?

*Note: The written testimony for the July 20 hearing focused on recent advances

in cancer treatment, as it was our understanding that this was the intended topic

of the hearing.

The body of research conducted before 1997 was, as described in a systematic review of the literature by respected epidemiologists, ‘‘inadequate to infer with confidence the relation between induced or spontaneous abortion and breast cancer

risk, but it appears that any such relation is likely to be small or non-existent.’’

Three points stood out in 1996. The first point was that the type of study (case-control interview study) that dominated the scientific literature at that time was sub-
55

1Women under-report abortions, yet breast cancer patients are more willing to acknowledge

a previous abortion than other women—a difference that produces ‘‘recall bias.’’

ject to a demonstrated bias (‘‘recall bias’’) 1 that tended to create an association

where such association might not actually exist. Also, many of the early studies had

no controls for other important risk factors. The second point was that the published

studies showed no consistency in findings—and those that did showed what epidemiologists term ‘‘a weak association’’ (a relative risk between 0.7 and 1.3), or difficult to distinguish from bias or chance. The third point was that it seemed unlikely

that the type of study that was needed—a study design unencumbered by recall

bias, such as a cohort study—could be performed in the United States.

Epidemiologists thus regarded with interest the very large study, reported in

1997, which examined medical records—not personal interviews—from the entire female population of Denmark. In Denmark, routinely maintained population registries of births, deaths, medical procedures, and cancer make it possible to compile

the data required on a large scale without recall bias and with great statistical precision. The study found no increased risk of breast cancer in the Danish women who

had recorded abortions, as compared with women with no record of abortion.

The NCI conducts and funds many epidemiologic studies of breast cancer. Often

included in the surveys and/or questionnaires are inquiries about a woman’s reproductive history which, as stated above in the response to Question 2, is a strong

determinant for breast cancer. These questions typically address her history of spontaneous abortion, induced abortion, or full term pregnancy. NCI has funded three

studies directly related to abortion as a possible risk factor. They are listed below:

Breast Cancer in Relation to Prior Induced Abortion (completed 1990) (PI: Daling—

Fred Hutchinson Cancer Research Center, Seattle)

Induced Abortion and Risk of Breast Cancer in Shanghai (completed 1997) (PI:

Thomas—Fred Hutchinson Cancer Research Center, Seattle)

Induced Abortion and Breast Cancer Risk (expected completion 1999) (PI: De-Kun—

Kaiser Foundation Research Institute, CA)

In summary, the scientific literature does not suggest that women who have even

one abortion show elevated risk. It remains true that a woman whose first pregnancy is interrupted, either by spontaneous or induced abortion, does not gain the

same degree of protection against breast cancer as the woman who is pregnant for

the first time at the same age and carries her first pregnancy to term; instead, she

has delayed her age at first birth. The biologic effect of abortion is seen by comparing two women who give birth for the first time at the same age, one of whom

had a prior terminated pregnancy. These two women have the same subsequent risk

of developing breast cancer, based on the epidemiologic data available today.

10. Research presented to the Committee shows that induced abortion

has been linked with increased risk of breast cancer. What has NCI done

to alert women that induced abortion has been consistently associated with

increased breast cancer risk? How has NCI focused its public information

on at-risk populations?

Experts at NCI and elsewhere find that the evidence suggests that induced abortion is not associated with an increased risk for breast cancer. Our information to

women concerned about breast cancer risk after abortion addresses the research

data to date, and includes discussions about data inconsistencies. We also emphasize the importance of a woman’s discussing her personal risk of breast cancer with

her physician.

In general, NCI reaches out to patients, their families, health care providers, researchers, and the public to bring them the most accurate, up-to-date cancer information. The NCI provides that information by telephone, on the Internet, through

the media, in partnership with other organizations, and through a wealth of printed

and audiovisual materials.

• The Cancer Information Service (CIS) answers about 500,000 calls a year at 19

regional offices. The toll-free number, 1-800-4-CANCER, connects English- and

Spanish-speaking callers with the office that serves their area. The CIS provides nationwide service to all 50 states and Puerto Rico. It also has an outreach program that develops partnerships with nonprofit, private, and other

government agencies at national, regional, and local levels. Two-thirds of CIS

partners focus on reaching minority populations.

• PDQ is NCI’s computerized database that gives patients, health professionals, and

the public quick and easy access to the latest treatment, supportive care,

screening, and prevention information, as well as descriptions of clinical trials

that are open for enrollment.
56

• NCI’s Office of liaison Activities works with national advocacy, voluntary, and professional organizations concerned about cancer to disseminate the latest, most

accurate cancer information, and collaborates with these groups in areas of mutual interest. These organizations influence their members, the media, the public, and policymakers.

• NCI is developing a publication on genetic testing to help people decide if testing

is right for them. NCI is also working to increase health care professional

awareness and knowledge of human genetics and related ethical, legal, and psycho-social issues.

• NCI develops media and print materials designed for distribution to a variety of

audiences. Some of these are designed specially for minorities and the medically

underserved and are often implemented as part of national campaigns. These

materials support the main message of a campaign (for example, women over

age 40 should have regular mammograms) but are designed to be used by community leaders. For example, some materials for mammography screening include posters in English for African-American, Asian, and Native American

women, and in Spanish, Vietnamese, Chinese and Korean. NCI also contributed

to a nationally syndicated Spanish radio show promoting breast and cervical

cancer prevention and detection.

11. I understand that the body of worldwide epidemiological research on

the link between abortion and breast cancer reaches back as far as 1957.

And the first such study conducted in the United States occurred as early

as 1981. Is it not a fact that a majority of these studies show an increased

risk (average about 30%) among women who have chosen abortion even

just once?

The only cohort study published before 1996 found a statistically significant negative association (that is, abortion was associated with reduced risk for breast cancer). Of the 18 case-control studies published through 1996, most found no statistically significant association, positive or negative. Most of these studies did not control for known risk factors, or were limited by inadequate or possibly biased reporting of abortions. Because a very weak overall association might obscure a stronger

one in a subgroup of women (perhaps young women), investigators also reported any

associations noted in subgroups, even though the number of those subjects was very

small. The subgroups noted to be at risk in one study were not found to be at risk

in other studies. Thus, even before the large Danish cohort study was published the

weight of evidence suggested no association, or a very weak one. There remains

some uncertainty about the relative risk for women with very late induced abortions. More data on this finding would be valuable.

12. The NCI website on ‘‘Abortion and Breast Cancer’’ states that ‘‘although it has been the subject of extensive research, there is no convincing

evidence of a direct relationship between breast cancer and either induced

or spontaneous abortion. Available data are inconsistent and inconclusive,

with some studies indicating small elevations in risk, and others showing

no risk associated with either induced or spontaneous abortions.’’

A. Please identify and provide copies of the ‘‘extensive research’’ to which

the website text refers. Was this research peer-reviewed?

I have attached copies of a systematic review of the literature published in 1996,

a Dutch case-control study published later, and the large Danish cohort study (Attachments 3, 4, and 5). Each of these papers contain an extensive bibliography

which, when taken as a whole, represent the body of literature used by NCI experts

to develop the fact sheet to which you refer. All of these papers were published in

peer-reviewed journals.
57

B. The website states that there is no ‘‘convincing evidence.’’ What are

NCI’s criteria for identifying research that would be considered ‘‘convincing’’? Are there statistical benchmarks that NCI uses to distinguish

evidence that is convincing and that which is not? How is this evidence

measured that would control for bias among researchers or program

evaluators?

C. Does NCI draw a distinction between ‘‘direct relationship’’ and ‘‘indirect relationship’’ in determining causality?

D. NCI states that ‘‘available data are inconsistent and inconclusive.’’ Are

the data inconsistent, or are the studies inconsistent? What accounts

for data that ‘‘are inconsistent and inconclusive’’? Has NCI attempted

to replicate studies that may have shown a link between breast cancer

and induced abortion?

E. The NCI website states that some studies indicate a ‘‘small elevation

in risk.’’ What does ‘‘small elevation in risk’’ mean in this context? By

saying there is a ‘‘small elevation in risk,’’ is NCI placing the risk on

a continuum between no risk and high risk? How does the ‘‘small elevation in risk’’ rank on a comparative risk analysis continuum? Based

on this continuum, what action has NCI or other Federal agencies

taken to warn consumers of cancer risk-factors that are comparable to

that of induced abortion? Does ‘‘small elevation in risk’’ mean ‘‘acceptable risk’’? How does NCI determine that something is an acceptably

small risk?

Epidemiologists use the terms ‘‘weak associations’’ or ‘‘small risks’’ to express assessment of whether an association is ‘‘real’’; that is, the probability that a factor

causes the development of disease. Epidemiologic studies can be subject to errors

of several types: biases in selection of study participants; biases in the observation

of comparative data (such as the recall bias so problematic in collecting interview

data on induced abortion); and statistical imprecision as the study size becomes

smaller. Thus, ‘‘small’’ or ‘‘weak’’ are terms associated with the level of error methodologically expected for (1) chance occurrence, (2) a particular feature of the disease

or the exposure, and (3) study design. The increased risk of developing breast cancer

associated with each risk factor (see Question 2, above, for examples) varies from

1.5 to 4 times average risk.

An association typically is estimated as the ratio of risks, or the ‘‘relative risk.’’

‘‘Relative risk’’ is the ratio of disease incidence in the exposed population to the incidence in the unexposed population. A relative risk of ‘‘1.0’’ means that women exposed and women unexposed to a factor have the same risk of developing disease.

It is a mathematical computation well-suited for assessing biologic connection. It is

not intended to address comparison of absolute risk to benefit, or to judge what is

acceptable risk to each individual. The NCI publishes widely the facts known about

possible breast cancer risks, but decisions about ‘‘acceptable’’ risks must be made

by a woman and her health care provider.

For the relationship between abortion and breast cancer, the most complete current summary of the uncertainty comes from the Danish population record study.

The authors estimate that the relative risk for breast cancer in women with a recorded abortion is most likely between 0.94 and 1.06, with a very narrow interval

of uncertainty because the study was very large. If a relative risk of ‘‘1.0’’ means

that women exposed and women unexposed to a factor have the same risk, then the

Danish population record study demonstrates that the women exposed to—and

those not exposed to—the risk factor (induced abortion) have the same risk.

In many case control studies, a relative risk of 1.3 (or equivalently, a protective

effect seen in a relative risk of 0.7) would be weak, small, or low. A relative risk

of 2.0 is moderate. For example, if the initial research suggestion of an overall relative risk of 1.3 for developing breast cancer after abortion were supported by large

and well-controlled epidemiologic studies, and otherwise fulfilled criteria for causality (see Question 12F. below), NCI would, as with other peer-reviewed information, make that available through all our mechanisms of information dissemination

(see Question 10, above). NCI takes its responsibility for the public trust very seriously. All peer-reviewed study data are considered carefully, continuously, and comprehensively before we will say with certainty that a factor imparts a cancer risk.

As discussed previously, the scientific literature to date does not suggest that

women who have even one abortion show elevated risk. Our publications currently

reflect this.
58

F. NCI also states that some studies indicate ‘‘no risk.’’ What level of ‘‘elevation of risk’’ is considered to be ‘‘no risk’’ by NCI? How is ‘‘no risk’’

distinguished from that of ‘‘small risk’’ when proving causality is so difficult?

Evaluation of causality requires consideration of various types of evidence. Whether an exposure causes cancer may be assessed via several similar schema, the most

common being the Bradford Hill criteria: strength of association, consistency, specificity, temporality, biologic gradient, plausibility, coherence, experimental evidence,

and analogy. In many case control studies, a relative risk of 1.3 (or equivalently,

a protective effect seen in a relative risk of 0.7) would be weak, small, or low. The

authors of the Danish study estimate that the relative risk for breast cancer in

women with a recorded abortion is most likely between 0.94 and 1.06, with a very

narrow interval of uncertainty because the study was very large. This falls below

the level of risk epidemiologists would consider weak, small, or low.

13. Is it true that epidemiologic research has found no overall link between spontaneous abortion and breast cancer? Is that not also consistent

with the fact that most pregnancies which abort spontaneously are characterized by subnormal estrogen levels, whereas normal pregnancy levels of

estrogen are several times higher than non-pregnant levels? Is it also true

that some form of overexposure to estrogen, which stimulates the growth

of both normal and precancerous breast tissue, is the mechanism by which

most of the known breast cancer risk factors operate?

Yes, it is true that research has found no overall link between spontaneous abortion and breast cancer. There are many causes of spontaneous abortion, and not all

of them are characterized by subnormal estrogen levels. Breast cancer is a cancer

that is hormonally responsive, but it is unclear that estrogen is the only hormone

involved. Other hormones may also play an important etiologic role.

14. The NCI website’s first paragraph concludes with the sentence: ‘‘The

scientific rationale for an association between abortion and breast cancer

is based on limited experimental data in rats, and is not consistent with

human data.’’ Is this data to which you refer the Russo and Russo 1980

study? Is it accurate to summarize that this study, where rats were all

given a chemical carcinogen, most of those rats which were allowed to bear

offspring did not get breast cancer, while most of those which had their

pregnancies surgically aborted did get breast cancer?

The data referred to in the NCI Fact Sheet on the Web site is the Russo & Russo

study data. For breast cancer studies, suitable animal models have not been found,

so extrapolating from animal data to the human model may not infer an absolute

comparison. Russo & Russo found that pregnant rats who carried to term developed

fewer mammary tumors than did rats who never were pregnant, or whose pregnancies were terminated.

15. The NCI website refers to studies finding ‘‘small elevations in risk’’ in

the link between abortion and breast cancer. A 1994 Howard University

study on African-American women here in the Washington, DC area

showed a more than three-fold increase in breast cancer risk with induced

abortion. That same study showed that the risk was almost five-fold for African-American women over 50 years old. Is it accurate to call that kind of

risk elevation ‘‘small’’?

Abortion was not a risk factor studied in the project referred to above. The risk

you cite was actually the risk associated with a family history of breast cancer

among women with two or more abortions. This was not the risk associated with

abortion.

Please do not hesitate to contact me if you have further questions.

Sincerely,

RICHARD D. KLAUSNER

Director

Attachments
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60
61
62
63
64
65
66
67

Mr. COBURN. I would make one clarifying point. So it is important to people that are not medical here. There are non-aggressive

forms of human papilloma virus; those are of no interest to us, because they have no effect. It is only those that are aggressive that

we are concerned with, and it is only those that cause cancer. So

that, when we discuss them in total, we diminish the importance

of the aggressiveness of those that do affect humans, and it is important for everybody, when we are asking a question about HPV,

we are talking about those that are carcinogenic or oncogenic, rather than those that aren’t.

The other point that I would make, and I think our panel made,

that is not the only cancer that they cause. We see cancer of the

vulva, cancer of the rectum, cancer of the larynx associated with

these same HPV subtypes.

And I would yield to the gentlelady from California.

Ms. ESHOO. Thank you for recognizing me, and I want to thank

each one of the witnesses that are here today because you have

given us highly informative testimony. I hope there are a lot of people that are tuned in or will hear this through a repeat program,

wherever they are in this country, because I think in listening, that

at least part the intent of this hearing is to educate. Educate, educate, educate.

The first request that I have, before I ask my question, is, Dr.

Lee, Dr. Valdiserri, could you from the CDC provide for me—and

perhaps the rest of the members of the subcommittee would like

this as well—I would love to have a list of who you contract within
68

my congressional district for the services that you provide. I was

deeply involved in those issues before I came to the House, and the

county board of supervisors, and established a whole network of

clinics in a major county in the Bay area. So I would like to know

who you are working with. Also, we should all be looking into

whether we can do public service announcements in our congressional districts on this. Because to the extent that we get this out,

and to the extent that we have something in place right now, and

to the extent that this subcommittee and full committee and the

Congress pass Mr. Lazio’s and Congresswoman Capps’ and my

original co-sponsorship of the legislation, we can really go after this

and be effective. So if you can do that, we would really appreciate

it.

[The information referred to follows:]

Question. List of recipients (CBOs, etc) of BCCEDP funds in Ms. Eshoo’s District

(14th District in CA—includes Palo Alto)

Answer. CDC funds the California Breast and Cervical Cancer Early Detection

Program (CBCCEDP) to:

• provide screening to medically underserved women for breast and cervical cancer • provide appropriate and timely diagnostic evaluations for women with abnormal

screening tests and treatment services if needed

• develop and disseminate public information and education related to the detection

and control of breast and cervical cancer

• improve training of health professionals in the detection of these cancers

• and finally, evaluate program activities through the establishment of surveillance

systems.

The CBCCEDP partners with many organizations throughout the State to provide

specific services for at risk women. One such partnership in the 14th District of

California is the Santa Clara Valley Center in San Jose, which has breast and cervical cancer screening providers located in Palo Alto. Women of the 14th District

may also choose to receive services from the CBCCEDP sites of Alameda County

Medical Center and San Francisco Department of Public Health.

Santa Clara Valley Center

P.O. Box 21949

San Jose, CA 95151-1940

Attn: Jennifer Sedbrook, (408) 289-9260

Alameda County Medical Center Fairmont Hospital Administration

15400 Foothill Boulevard

San Leandro, CA 94578

Attn: Carol Oakley, (510) 667-7848

San Francisco Department of Public Health

101 Grove Street, Room 321

San Francisco, CA 95151-1940

Attn: Diane Carr (415) 554-2878

Question. The National Breast and Cervical Cancer Early Detection Program’s

legislation (Public Law 101-354) provides states with funds to offer screening services to women of low-income. What mechanisms are in place to provide treatment

to women who need it?

Answer. Ensuring that all women with abnormal screening results receive adequate follow-up and a definitive diagnosis is a crucial component of the National

Breast and Cervical Cancer Early Detection Program (NBCCEDP). Thus, diagnostic

services funded through the program include diagnostic mammography, breast

ultrasound, breast biopsy fine needle aspiration, colposcopy, colposcopy-directed biopsy and endocervical curettage.

The legislation that authorizes the NBCCEDP does not allow resources appropriated for the program to be used for treatment. However, participating health

agencies are required to identify and secure resources for diagnostic follow-up services that the program does not cover and for cancer treatment services for women

in need, regardless of their ability to pay. CDC provides careful oversight to assure

that women who need treatment receive it.

Analysis of program data for all abnormal screening mammograms reveals a median of 36 days between the initial screening mammogram and final diagnosis, and
69

a median of 9 days between diagnosis of breast cancer and treatment. Additionally,

surveillance data show that 96 percent of the women diagnosed with invasive or in

situ breast cancer have initiated treatment. Of the remaining 4 percent, 2 percent

reportedly refused care, 1 percent had a provider recommendation that treatment

was not currently indicated, and 1 percent were lost to follow-up.

In addition, CDC contracted with Battelle Centers for Public Health Research and

Evaluation and the University of Michigan to document the range of systems and

strategies used by states to obtain resources for treatment and ensure that women

diagnosed with cancer or precancerous lesions receive timely and appropriate followup and treatment services. Seven state programs (California, Michigan, Minnesota,

New Mexico, New York, North Carolina, and Texas) were studied in depth, ending

in December 1997. Almost 200 people were interviewed; more than half of them

were screening, diagnostic service, and/or treatment providers in local communities.

The study results show that innovative and creative approaches have been implemented to identify and secure resources for follow-up and treatment services.

Women diagnosed with cancer through the NBCCEDP are receiving treatment.

Without exception, study respondents reported that of their clients diagnosed with

breast cancer or invasive cervical cancer, all women who have wanted treatment

have indeed initiated cancer therapy.

Creative partnerships and responses to the lack of NBCCEDP resources for some

diagnostic services and all treatment services have been developed in programs at

the state, local, and provider levels. Implemented strategies are very similar for

breast and cervical cancer, although funding from state legislatures and private

foundations is more prevalent for breast diagnostic services than for cervical diagnostic services or for cancer treatment in general. Additionally, each of the seven

states studied currently has some type of fund, centralized at the state level, that

supplements the services provided by the NBCCEDP. Many financial barriers to diagnostic follow-up and some for cancer treatment have been reduced.

Findings suggest that state programs and their partners have invested significant

amounts of time and effort to develop systems of care for diagnostic follow-up and

treatment, and that these systems appear to be working. Tremendous effort is involved in developing, implementing, and maintaining strategies and systems for

these services. Rarely is there a standardized or set way that a state or even a facility uses to obtain services women need that are not covered by the NBCCEDP. Efforts typically are tailored to an individual client’s needs and resources.

The goal of the NBCCEDP is to reduce mortality from breast and cervical cancers,

and the success of this effort hinges on the identification and treatment of early

stage cancers. As they have in the past, CDC and its state partners in the

NBCCEDP will continue to give priority to this critical aspect of the early detection

effort.

STRATEGIES FOR PROVIDING FOLLOW-UP AND TREATMENT SERVICES IN THE NATIONAL

BREAST AND CERVICAL CANCER EARLY DETECTION PROGRAM UNITED STATES, 1997

The Breast and Cervical Cancer Mortality Prevention Act of 1990 (Public Law

101-354) authorized CDC to establish the National Breast and Cervical Cancer

Early Detection Program (NBCCEDP) to increase screening services for women at

low income levels who are uninsured or underinsured (1). Although the NBCCEDP

covers most diagnostic services that women need after receiving an abnormal mammography or Papanicolaou (Pap) test result, the program does not reimburse for

breast biopsies. In addition, the Act prohibits the use of NBCCEDP funds for cancer

treatment. Participating health agencies must ensure that NBCCEDP clients receive timely, appropriate diagnostic and treatment services. In 1996, CDC began a

case study to determine how early detection programs in seven participating states

(California, Michigan, Minnesota, New Mexico, New York, North Carolina, and

Texas) identified resources and obtained diagnostic and treatment services. This report summarizes the results of the study (2), which indicate that respondents in

these states reported that treatment had been initiated for almost all NBCCEDP

clients in whom cancer was diagnosed. However, respondents also considered the

strategies used to obtain these services as short-term solutions that were labor-intensive and diverted resources away from screening activities.

In the seven states, NBCCEDP sponsored screening services had been provided

for ≥3 years, and breast cancer had been diagnosed in ≥60 women. The states were

selected to provide a range of geographic locations, a combination of urban and rural

populations, and racial/ethnic diversity among program clients. Researchers conducted semistructured interviews with 192 persons affiliated with the seven state

programs. Of these interviewees, 120 (63%) were providers of screening, diagnostic,

and/or treatment services; 58 (30%) were state program staff; and 14 (7%) were coa-
70

lition members. Interviews included topics such as guidelines related to diagnostic

and treatment services, strategies used to obtain and pay for services, level of effort

required to secure these services, and changes in strategies over time. Each interview was tape recorded and transcribed. Using a systematic scheme derived from

the research questions, three researchers coded the same transcripts until an interrater agreement of 80% was reached. Thereafter, all transcripts were coded independently. Coding results were entered into text analysis software that sorts text

from transcripts into sets of information, themes, and evidence relevant to the specific research questions (3). The results reflect a synthesis of the interviewees’ responses. Respondents described several strategies used to ensure necessary diagnostic and treatment services for women screened through the NBCCEDP. State

level strategies in all states included 1) computerized tracking and follow-up systems that used program surveillance data to identify and manage clients in need

of diagnostic and treatment services; 2) provisions in contracts requiring screening

providers to arrange for diagnostic follow-up and treatment before screening women;

and 3) arrangements with provider groups and state professional associations for

free or reduced cost services for NBCCEDP clients. All states also had access to public or private funds to help support services not covered by the program; such revenue sources included state appropriations from general or tobacco tax revenues or

funds from private foundations. These funds were available primarily for breast diagnostic services.

Local strategies tailored to the needs of individual clients were used to obtain diagnostic and treatment services. Common strategies reported by respondents included the following: providers billed public or private insurance plans; providers or

local health departments helped clients apply for public assistance programs; providers referred clients to public hospitals; county indigent care funds and hospital

community benefit programs financed services; clients received services through individually negotiated payment plans; and clients paid reduced or full fees for services.

Respondents strongly supported the continued growth of NBCCEDP and its goals

but expressed several concerns. First, considerable time and effort were involved in

developing and maintaining systems for diagnostic follow-up and treatment. Second,

the process of identifying available resources within states for diagnostic and treatment services was considered labor-intensive. Third, the lack of coverage for diagnostic and treatment services negatively affected recruitment of providers and restricted the number of women screened. Fourth, respondents believed that an increasing number of physicians will not have the autonomy, because of changes in

the healthcare system, to offer free or reduced fee services to NBCCEDP clients.Respondents reported that arrangements for treatment were made for almost

all NBCCEDP clients who received a diagnosis of breast cancer or invasive cervical

cancer. Respondents stated that some women experienced time delays between

screening, definitive diagnosis, and initiation of treatment. State program officials

reported that, according to 1992-1996 surveillance data, small numbers of clients in

whom cancer was diagnosed (i.e., from three to 13 women in each state) subsequently refused treatment. Because these clients were not interviewed, it could not

be determined whether financial barriers contributed to their decisions to refuse

treatment or their loss to follow-up.

Respondents were concerned that the NBCCEDP did not provide funding for all

diagnostic procedures and treatment for the diseases for which clients were being

screened; approaches for delivering services were fragmented; and the process of obtaining resources required substantial effort at the state, local, and provider levels.

Respondents reported that the continuation of every strategy for diagnostic and

treatment services beyond the next few years is uncertain. Reported by: PM Lantz,

PhD, Univ of Michigan School of Public Health, Ann Arbor. LE Sever, PhD, Battelle,

Centers for Public Health Research and Evaluation, Seattle, Washington. Program

Svcs Br, Office of the Director, Div of Cancer Prevention and Control, National Center for Chronic Disease Prevention and Health Promotion, CDC.

Editorial Note: During July 1991-March 1997, the NBCCEDP provided 576,408

mammograms to women aged ≥40 years, and 3409 cases of breast cancer were diagnosed. During this same period, the program provided 732,754 Pap tests; 23,782

cases of cervical intraepithelial neoplasia and 303 cases of invasive cervical cancer

were diagnosed. These totals included women referred to the program for diagnostic

evaluation of an abnormal screening result. The NBCCEDP internal estimates suggested that during this period only 12%-15% of uninsured women aged 40-64 years

in the United States had been screened by the program (CDC, unpublished data,

1997).

Screening alone does not prevent cancer deaths; it must be coupled with timely

and appropriate diagnostic and treatment services. The Congressional mandate for
71

NBCCEDP requires grantees to take all appropriate measures to ensure provision

of services required by women who have abnormal screening results. CDC provides

funds for case management to help these women access healthcare services. To increase the comprehensive nature of the program, CDC recently approved the use of

NBCCEDP funds for breast biopsies.

The results of this study indicate that state health departments and their partners in the seven states had developed a wide range of strategies for diagnostic and

treatment services in the absence of program resources. However, the time and effort required to arrange and maintain these services diverted resources away from

screening activities.

This study was subject to at least two limitations. First, the results were based

solely on the experience and opinions of informed professionals affiliated with the

program and did not include the perspectives of NBCCEDP clients. Second, the results may not reflect the program experiences in other states. Case study methods,

however, are an appropriate and well-accepted approach to gaining in depth understanding of complex programs in realife situations (4). The validity of the findings

was enhanced by developing standard instruments to guide the semistructured

interviews, protecting the confidentiality of respondents’ remarks, using interview

transcripts for data analysis rather than relying on interviewer notes, and obtaining

feedback concerning state summary reports from respondents.

As more women are screened by the NBCCEDP, a greater burden will be placed

on participating health agencies, providers, and other partners to obtain resources

for breast and cervical cancer treatment. Case management services will continue

to be essential in helping underserved women overcome financial, logistical, and

other barriers to receiving these services. Other long term solutions to ensure that

women in the program receive necessary treatment services are being pursued.

References

1. Henson RM, Wyatt SW, Lee NC. The National Breast and Cervical Cancer Early Detection

Pro-gram: a comprehensive public health response to major health issues for women. J Public

Health Management and Practice 1996;2:36-47.

2. Lantz PM, Macklem DJ, Hare M, Richardson LC, Sever LE, Orians CE. Follow-up and

treatment issues in the National Breast and Cervical Cancer Early Detection Program: results

from a multiple-site case study—final report. Baltimore: Battelle, Centers for Public Health Research and Evaluation, 1997.

3. Miles MB, Huberman MA. Qualitative data analysis: an expanded sourcebook. 2nd ed.

Thou-sand Oaks, California: Sage, 1994.

4. Yin RK. Case study research: design and methods. Sage: Newbury Park, 1989.

Strategies for Providing Follow-Up and Treatment Services in the National Breast

and Cervical Cancer Early Detection Program—United States, 1997. Lantz PM, Sever

LE, Henson R, Lee NC. MMWR, March 17,1998; Vol. 47. No. 11. pp 215-218

Ms. ESHOO. When the CDC does the early detection and the

screening and something is found, do you have any certain way to

set women on a path outside of that? Tell me what you do.

Ms. LEE. Yes. Yes, I will. Well, as you know, the 1990 act specifically forbade the use of Federal Government funds to pay for treatment.

Ms. ESHOO. Well, we know that. That is why the bill is——

Ms. LEE. Yes, right, and that’s why you have introduced this bill.

We are allowed to pay for diagnostic services, and so we do provide

central diagnostic services.

Ms. ESHOO. But once you do what the 1990 legislation set up,

and I’m not suggesting——

Ms. LEE. Okay, so then we diagnose.

Ms. ESHOO. [continuing] for giving you permission to go get into

trouble to go beyond it. Do you have set information for women

or——

Ms. LEE. Yes, we actually have a published paper because we

have done a study on this. We have a partnership with our health

agencies, the health agencies, the American Indian tribes, et

cetera, and as part of that partnership, it is the responsibility of

the State health agency to assure that all women diagnosed with
72

cancer or a pre-cancerous condition receive the treatment that they

need.

Ms. ESHOO. Well, it is not happening, but that is not your fault;

it is that we haven’t taken the next step. But that’s instructive to

me, because I don’t think it is happening.

Ms. LEE. Well, we actually have a study that was published last

year——

Ms. ESHOO. That says——

Ms. LEE. [continuing] that says, by and large, it is happening.

Ms. ESHOO. That they all got treatment?

Ms. LEE. Yes, except for the few, less than 10 percent of

women——

Ms. ESHOO. Well, is it on a timely basis?

Ms. LEE. Yes, it is on a timely basis. There are some——

Ms. ESHOO. I’d like to see that.

Ms. LEE. Yes, I would be happy to provide you that.

Ms. ESHOO. I’m not here to question you. I’m here to question

some of the outcomes and the results.

Ms. LEE. Right. We feel very good that we are getting—but the

problem is, it is a very tenuous system. We really need the kind

of help that your bill may provide for us. But because they have

to put it together with a lot of charity, donated charity case from

this provider——

Ms. ESHOO. Well, I think the system, at best, once it comes to

treatment, is unpredictable Dr. LEE. Yes, absolutely.

Ms. ESHOO. It is a patchwork quilt at best—if you even want to

bring the word ‘‘best’’ into this. I think that families and women

in this country deserve much better. I mean, if we can get to the

moon, we can do something about this, and we got to the moon a

long time ago.

Let me go to another question, because I think I probably don’t

have that much time left. To Drs. Lowey and Trimble, in section

106 of H.R. 358, the Patients’ Bill of Rights, it calls for the requirement of managed care providers to pay for treatment provided in

the clinical trial. In your view, would enactment of such a provision

expand access to clinical trails and speed up research aimed at preventing, treating, and curing cervical cancer? I mean, we are talking about screening; then we are talking about treatment. We know

that a lot of the treatment isn’t there or isn’t paid for; there is

underinsurance for it. But the fact of the matter is that we don’t

have a cure for this.

So, can you maybe just comment on that part of the legislation?

I think it’s a very important section, but I would like to know what

your views are about it.

Mr. TRIMBLE. Only 2.5 percent of adults in the United States

with cancer are enrolled on cancer treatment trials, and the National Cancer Institute has been working closely with a number of

third-party payers to encourage them to pay for the patient care

costs associated with these clinical trials. The NCI has never had

the funds to pay for patient care costs. We pay for data management or some of the costs of data management.

We have had reasonable success with some of the third-party

payers. We have worked out agreements with the Veterans’ Administration and the Department of Defense, so that the patients that
73

they cover can have access to our clinical trials. We have not yet

been able to reach an agreement with the Health Care Financing

Administration, and we have continued to work with the HMOs,

but certainly we are supportive of all efforts to gain all Americans

access to our trials.

Ms. ESHOO. So this would be——

Mr. COBURN. Would the gentlelady yield for a minute?

Ms. ESHOO. Well, I don’t have any time to yield, Mr. Chairman.

Mr. COBURN. Well, I will be very benevolent with the time if we

can.

We have a cancer patient, a survivor, who is going to testify, and

I would like to ask you all if you would remain there until the rest

of our committee can finish their questions, and if I can have unanimous consent to have her come and give her testimony now, because she has her flight in a very short time; otherwise, we will

not be able to obtain her testimony.

Ms. ESHOO. Absolutely. Thank you for the time and thank you

to the panel for your words and professionalism.

Mr. COBURN. Ms. Piker, would you mind coming forward, please,

and giving us your testimony?

Mr. LAZIO. Mr. Chairman, could I just ask for unanimous consent

to make a remark for about 30 seconds?

Mr. COBURN. Yes, sir.

Mr. LAZIO. I am so conflicted. I am supposed to be chairing the

committee meeting across the hall right now. Just two quick remarks and they are: First of all, the need to get more adults in

clinical trial, I think, is made all the more compelling because of

the success in childhood cancer. The amount of children that are

in clinical trials, I think it is up around the 90’s, either in clinical

trials or in NIH protocol hospitals, and the success rates, especially

in certain leukemias, I think really bear out the fact that we need

to do much better in terms of getting adults into clinical trials.

The second point is—this is really in response to Ms. Lee’s comments about care for those women who receive bad news after they

have gotten screening through the CDC program—is that, actually,

the timeliness is much in question by a number of advocate groups,

about whether they are getting the treatment in a timely manner,

and whether it is done in a way that doesn’t accelerate or compound the stress and anxiety that women are under.

For example, many women that we have talked to have incurred

substantial debt, and we are talking about women, obviously, who

are at the lower-income levels, minimum wage people, waitresses,

people who have no hope of wiping out a $20,000 debt. And so I

would not want to leave the impression that what we have here is

a system of care that is reliable and that is timely and that does

not compound the stress that women face when they find out that

they have a malignancy.

Thank you, Chairman, for your indulgence.

Mr. COBURN. Ms. Piker.

STATEMENT OF LINDA GRACE PIKER, CERVICAL CANCER

SURVIVOR

Ms. PIKER. Mr. Chairman, thank you for inviting me to share my

experience with cervical cancer with this committee. I speak today
74

as a cervical cancer survivor, a co-founder of a gynecological cancer

support group, a cancer advocate, the Chair of the Kentucky Breast

Cancer Coalition, which addresses both breast cancer and other

women’s cancer in the Commonwealth, and most of all, I speak as

a friend and a confidante to numerous women who have been

touched by this disease. I have seen the despair and the destruction that cervical cancer has caused these women, their families,

and their friends. There are some stories that I’ll never forget.

I’ll never forget the beautiful young woman who was about 30

years old, whose physician called me and asked if I could talk to

her, and when I talked to her, I was totally empty handed. She had

had a pelvic exenteration at age 32. I also talked to another woman

who had received the same treatment who was 40 years old. I

think these are some of the treatments that nobody has any idea

take place. I mean, the majority of the public does not.

And I’ll never forget another beautiful young woman who came

to speak to the Cervical Cancer Advisory Committee just weeks before her death, and I knew the man that was deeply in love with

her and I know how much despair he went through after this.

In addition to the original diagnosis of cervical cancer, these

women are at increased risk for vaginal, vulva, and anal cancers.

One woman who was first diagnosed with cervical cancer, and then

vulva cancer a few years later, stands out in my mind. She had the

toughest exterior. But when you got to know her and you really listened to her, she had despair; she was embarrassed, and the fears

were all there. She fought long and hard, but eventually she died.

These are only a few of the women I would like to represent.

These deaths were needless. If diagnosed early, cervical cancer has

a 5-year survival rate of approximately 90 percent. Most importantly, with proper screening and with treatment, cervical cancer

is a preventable disease. We need to educate women on the risk

factors for the disease, screening, and, if necessary, where to find

information, treatment, and support.

In addition to the shock of being diagnosed with cancer in September 1990 when I was 44 years old, I could not understand how

this could have happened. Since I was 19 years old, I had received

annual Pap tests. I had had no problems. The more I read about

the disease, the more confused I became, and the more frightening

the issue became for me. Did I have an aggressive tumor? Would

I live to see my 10-year-old son grow up? My gynecologic oncologist

kept saying, ‘‘You’ll be fine, Linda. You are going to have a radical

hysterectomy with regular followup.’’ Well, for about the next year,

I was very frightened because I couldn’t figure out why this would

happen; I did everything you were supposed to do; what was happening?

And then to alleviate my fears, I happened to talk to one of the

fellows who had worked with me from the beginning of my cancer,

and he said, ‘‘Okay, Linda, what you really need to do is get your

Pap smear slides, let’s look at them, and I can tell you if it’s aggressive and we will follow you more closely, and if not, this should

give you some peace of mind.’’

Well, we had moved to Kentucky the previous year, and so I had

to call my former physician’s office and ask for my slides to be sent

to Lexington, Kentucky. I was given the address of a laboratory in
75

California. When I called, there was no listing for the lab, and this

was even more confusing. I just could not understand, you know,

and so I called back to the physician’s office and I said, ‘‘There’s

no listing.’’

Well, to shorten my long story, I found out that my physician

had been sending the Pap slides to a lab in California that was allegedly closed because of poor quality assurance. Had I known the

name of the lab my Pap slides had been sent to, I could have read

about it, because they were named in The Los Angeles Times and

The Wall Street Journal. Physicians were not liable for the Pap

test; therefore, it is my understanding that some physicians decided not to notify their patients that the physicians had sent the

patient’s Pap slide to this lab.

My cancer was diagnosed when I had a Pap test the following

year and my Pap slides were read by a different facility in Lexington. I spoke to my physician out of State about notifying other

patients. We had quite a long discussion. It took me three phone

calls to get to talk to the person, but my physician was not receptive to doing this at that time.

I suppose this was the crucial experience of my becoming an advocate for myself and other women. Not only do women need to be

educated about the risks associated with cervical cancer, but they

also need to know what questions to ask about screening methods

and their laboratories.

Since 1993, I have worked in the public health arena, where I

focus on ways to bring women into local health departments for

breast and cervical cancer screening. I also work with health departments to eliminate missed opportunities for screening of current clients. For approximately the last 3 years, I have worked

with community cancer coalitions which have unique ways to target women in their communities for breast and cervical cancer

screening. Cooperative partnerships and education are key components in their success for increasing the number of breast and cervical cancer screenings in the communities.

For any education campaign addressing the issue of human papilloma virus, or HPV, a clear message will need to be presented in

a sensitive manner; otherwise, an ill-conceived education campaign

might well become a barrier for women seeking screening.

As I leave here today, I thank you for holding a hearing on cervical cancer. As a mom of a childhood cancer survivor and relative

to friends or individuals with the various types of cancer, I often

call myself the generic cancer survivor. Although I am grateful to

this committee for addressing the issue of cervical cancer, I think

that a more comprehensive approach to fighting the war on cancer

would be more effective. I have never been a cancer survivor who

wanted to fight the body part wars. I look forward to the day when

we all unite and fight cancer together. Thank you.

[The prepared statement of Linda Grace Piker follows:]

PREPARED STATEMENT OF LINDA GRACE PIKER

Mr. Chairman, thank you for inviting me to share my experience with cervical

cancer with this committee. I speak today as a cervical cancer survivor, confounder

of a gynecological cancer support group, cancer advocate, the chair of the Kentucky

Breast Cancer Coalition, which addresses breast cancer and other women’s cancer

issues in the Commonwealth, and, most of all, I speak as a friend and confidant
76

to numerous women who have been touched by this disease. I have seen the despair

and destruction that cervical cancer has caused to these women, their families, and

friends. There are some stories I’ll never forget: the beautiful young woman in her

thirties who had a pelvic exenteration or the distressing call from a forty-year-old

woman who had undergone the same treatment. I’ll never forget one beautiful

young woman who spoke to a cervical cancer advisory committee only weeks before

her death or the young man who was devastated by her death. In addition to their

original diagnosis of cervical cancer, these women are at increased risk for vaginal,

vulva or anal cancer. One woman, who was first diagnosed with cervical cancer and

then vulva cancer, stands out in my mind. She was alone, had no medical insurance,

and had a low paying job prior to her illness. She had a very tough exterior, but

when you got to know her and listened to her, the despair, embarrassment, and

fears were all there. She fought long and hard, but she eventually died. These are

only a few of the women I would like to represent. These deaths were needless. If

diagnosed early, cervical cancer has a five-year survival rate of approximately 90%.

Most importantly, with proper screening and treatment, cervical cancer is a preventable disease. We need to educate women on the risk factors for the disease, screening, and, if necessary, where to find information, treatment, and support.

In addition to the shock of being diagnosed with cancer, in September 1990, when

I was forty-four years old, I just could not understand how this could have happened. Since I was nineteen years old, I had received annual Pap tests. I’d had no

problems. The more I read about the disease, the more confusing and frightening

this issue became for me. Did I have some aggressive tumor? Would I live to see

my ten-year-old son grow up? My gynecologic oncologist kept saying I’d be fine. I

would have a radical hysterectomy and regular follow-up. To alleviate my fears of

an aggressive cancer, I called my former physician’s office and asked that my slides

be sent to my physician in Lexington, KY. I was given the address of a laboratory

in California. When I called, there was no listing of the lab. I was even more confused. To shorten this story, I found out that my physician had been sending the

Pap test slides to a lab in California that was allegedly closed because of poor quality assurance. Had I known the name of the lab my Pap test slides had been sent

to, I could have read about the lab in the Los Angeles Times or the Wall Street Journal. Physicians were not liable for the Pap test; therefore, it is my understanding

that some physicians decided not to notify their patients that they had sent their

slides to this lab. My cancer was diagnosed when I had my Pap test the following

year and a lab in Lexington read my slides. I spoke to my physician about notifying

other patients, I did not feel that the physician was receptive to doing this at that

time. I suppose this was the crucial experience in my becoming an advocate for

other women and myself. Not only do women need to be educated about the risk

factors associated with cervical cancer, but also they need to know what questions

to ask about screening methods and laboratories.

Since 1993, I have worked in the public health arena where I focus on ways to

bring women into local health departments for breast and cervical cancer

screenings. I also work with health departments to eliminate ‘‘missed opportunities’’

for screening our current clients. For approximately the last three years, I have

worked with community cancer coalitions, which have found unique ways to target

women in their communities for breast and cervical cancer screenings. Cooperative

partnerships and education are key components in their success for increasing the

number of breast and cervical cancer screenings in their communities. For any education campaign addressing the issue of human papilloma virus (HPV), a clear message will need to be presented in a sensitive manner. Otherwise, an ill-conceived

education campaign might well become a barrier for women seeking screening.

As I leave here today, I thank you for holding hearings about cervical cancer. As

a mom of a childhood cancer survivor and relative or friend of individuals with various types of cancer, I often call myself the ‘‘generic cancer survivor.’’ Although I

am grateful this committee is addressing the issue of cervical cancer, I think that

a more comprehensive approach to fighting the war on cancer will be more effective.

I’ve never been a cancer survivor who wanted to fight the ‘‘body part wars.’’ I look

forward to the day when I can see us all united to fight cancer. Thank you.

Mr. COBURN. Thank you, Ms. Piker. I will defer any questions to

the ranking member. Do you have any questions of the witness?

Any other members of the committee have questions for this witness?

[No response.]

Ms. Piker, thank you for being here.

The gentleman from Tennessee is recognized.
77

Mr. BRYANT. Thank you. Let me add my appreciation, Ms. Piker,

before you go back to Kentucky, I assume, for your being here and

also for the very learned panels that we have had here.

At this time, I have been asked by the chairman if I would yield

my time to the chairman. I would be happy to do that.

Mr. COBURN. I thank the gentleman. I just have a couple other

questions that I kind of want to follow up on. I introduced into the

record a few moments ago a letter we received on the 19th from

Dr. Klausner. The testimony today—we have two different testimonies. One testimony is that a condom is effective in HPV, and

one that says it is not. I wonder if any of the panel would help this

committee know what this answer is to that question. Anybody

have an answer for that?

Mr. VALDISERRI. Let me start. I think it’s an extremely important

question, and I think it is easy to understand why there might be

some confusion on it.

What we know in general—and I’m talking generally now; I’m

not talking about HPV—but what we know in general about

condoms and viruses lead us to believe that the condom has at

least a theoretical possibility of preventing transmission if the lesion is confined to the penis that is covered by the condom. Now,

there are a lot of ‘‘if’s.’’ Obviously, there are a lot of ‘‘if’s’’ and conditions. Given that HPV infection may not result in a visible lesion

and that typically that there are multiple sites of infection on the

genitalia, I think that what you will see in most of the articles or

textbooks or review articles is the statement that there have not

been definitive studies, prospective studies, that have evaluated

condom efficacy in terms of preventing HPV. So, I think that’s why

there is that confusion.

Mr. COBURN. I would quote Dr.—and you don’t have the benefit

of this letter, but Dr. Klausner states additional research efforts by

NCI on the effectiveness of condoms in preventing HPV transmission are not warranted. And he states in his letter why it’s not.

It’s because if you, in fact, are infected, the scrotum is infected as

well.

If I could make one point, you all are behind the curve on this.

The epidemic is way ahead of you. Is that not really true? I mean,

the epidemic associated with evasive HPV and cervical dysplasia is

ahead of where we are. We really don’t have the knowledge on this

sexually transmitted disease that we have on many others. Is that

a fair statement?

Mr. VALDISERRI. In some areas, I would agree with certain aspects of that statement. Definitely in terms of some of the condom

efficacy studies and, as we discussed earlier, in terms of some of

the surveillance information, especially about specific types of

HPV.

Mr. COBURN. I guess if I had my heart of hearts, what I would

want everybody to know is that we really don’t know all the answers right now about HPV and that there is an epidemic of dysplasia out there. All you have got to do is ask any pathologist what

they are seeing in their Pap labs. I mean, it is growing like crazy

right now. We are seeing tons of carcinoma in situ, and I know the

studies are ongoing in that.
78

The fact is, we don’t know. We have an unknown quality right

now. As we talk about access, there is not one woman that I don’t

want to have access to a high quality Pap smear and physical exam

every year. I want that for every woman in this country, those that

have been sexually active and those that have not. But I also want

them to have the knowledge about what the danger is of this disease.

I mentioned earlier a Green Journal study in 1987 or 1988,

where they did culture HPV, one of the aggressive serotypes from

amniotic fluid, where they do, can culture this same virus in the

reproductive tract of newborn babies, male and female, it is an important consideration that our highest institutions have not aggressively researched.

And so, my point—and I’m going to submit a list of questions,

and they will be given to each of you and then I’ll ask that we divide those up to the appropriate—actually, I’ll try to get them divided up to the appropriate expert that we have here today.

You know, we really ought not to worry about where we have

been, but we really ought to get busy about where we need to go

on human papilloma virus. I have been in practice 16 years. I have

never seen anything like it in my office. And if you go talk to practicing physicians that are in the middle low-income and with teenagers and Medicaid patients, we are seeing an explosion of this disease right now. And it is aggressive types. I mean, we are seeing

a ton of high-grade dysplasia.

So, my wish is that, tell us what we need to do so that we really

know what the science is, because I don’t believe it’s out there right

now.

Mr. VALDISERRI. I don’t want to be parochial, but I couldn’t agree

with you more. I do want to say, again, that we have been working

at CDC and our center and with our colleagues on trying to develop

a specific plan focused on—we looked first at herpes, which is not,

obviously, not the focus of this meeting, but now we are doing the

same thing with HPV. We have this big meeting in April with a

lot of experts coming in and we have actually generated close to 45

specific questions that we want these people to grapple with.

So, I couldn’t agree with you more, Dr. Coburn, that there are

still some issues that we have to invest in getting answers to.

Mr. COBURN. Before I would yield to anybody that would like additional time—we know that a condom is not preventive. I mean,

we know that right now. Unless we wrap everybody in saran wrap,

we are not going to prevent human papilloma virus.

Mr. VALDISERRI. And we also know that there is more than HPV

as a sexually transmissible disease. So we have this complex issue

of—it is not an issue if people are abstinent, but we have this complex issue for people who are sexually active, where condoms can

be helpful in preventing other STDs. How do we craft the message

so that they know that it might not necessarily protect against

HPV? And then they will say, ‘‘Well, gee, why even bother?’’

Mr. COBURN. Very easy. It is a condom won’t protect you from

human papilloma virus, the No. 1 cause of cervical cancer in this

country, and it affects 50 percent of those people who are sexually

active, regardless that it might protect you from HIV. If it won’t

protect you from the No. 1, then it’s a false safe sex message. It
79

doesn’t work. And so we can continue down that line of false assumptions, but you are going to find the science that will say it

doesn’t work, and we know it doesn’t. The practicing physicians out

there today know it doesn’t work.

So, all I’m saying is, we need to look at the data completely from

a pure scientific—and give us a plan to where we can give treatment, whatever we do. I treat kids who are going to be sexually

active, if they tell me they are; I give them very tool I can. But the

point is, is we can’t send a false message about HPV.

Mr. VALDISERRI. Well, we don’t intend to send a false message.

Mr. COBURN. Thank you. And the ranking member, Mr. Brown.

Mr. BROWN. Mr. Chairman, I’m a little concerned about the sort

of exchange and the questions, the letter you have submitted, and

I’m glad that we finally got a copy of it. I understand, from what

you just said, you will submit some more questions of this panel.

I would hope that this subcommittee would—and I don’t lay the

blame at your feet and I appreciate your genuineness about this—

but would see fit to share with the minority some of this information. This letter, it started off—you posed 15 questions about the

possible relationship of induced abortion to breast cancer; these are

pretty volatile issues that people have very strong feelings about.

I know, it’s more than that; I understand that, but that was the

lead sentence in it. We just found out about this a month after it

was received by Mr. Bliley.

I would just like to encourage this subcommittee on the majority

side to make sure the minority, particularly when we are talking

about issues that people care about and the discussion you had

with Dr. Valdiserri, just now, that we have this information ahead

of time.

Mr. COBURN. Mr. Brown, the staff tells me that you all received

a copy of that letter the day it was sent.

Mr. BROWN. My understanding from our staff is that we received

the letter that you sent to the doctor, that Chairman Bliley sent

to HHS, but we have not gotten the response until today.

Mr. COBURN. If, in fact, you didn’t, that is a grave error that

should be corrected by this committee, and you should have the response and any letter that comes to this committee, based on a letter from it. As you know, I am not in the position to empower that

that happens each time.

I would just like to ask if any of the other members of this panel

would like to offer anything for us, tell us where we know what we

need to do, make recommendations outside of what you have made

in your testimony.

Mr. VALDISERRI. May I just again say, please don’t forget, in addition to the basic research needs, don’t forget the whole host of

operational research questions; and that’s fairly parochial, because

it is what we tend to do at CDC. But our last interchange about

how do you craft a message for sexually active people, about what

condoms can and can’t do, given that in the real world there are

many, many STDs, as a perfect example of the kind of work that

is very important—so, I would like to, again, go on record saying

that that is a need that we have.
80

Mr. COBURN. The gentlemen from New York is here. Would you

like to ask questions, Mr. Towns? Yes, the gentleman is recognized

for 5 minutes.

Mr. TOWNS. Thank you very much, Mr. Chairman.

What population is considered to be at high risk for developing

cervical cancer? Anybody?

Ms. LEE. There are lots of risk factors. Probably the strongest

risk factor that is sort of the cause of it is what we have been talking about today, which is infection with certain subtypes of human

papilloma virus. Another very important risk factor is failure to be

regularly screened with Pap smears. Then, you find higher rates of

cervical cancer developing, and women dying from it, in foreignborn women in the United States and women who are Hispanic,

who are African-American, and who are from certain subpopulations from Asia. You also find cervical cancer to occur, and especially cervical cancer deaths, to occur more often in older women.

Mr. TOWNS. Decreasing the incidence of cervical cancer 30 percent, is that dependent on treatment, new treatment methods,

or——

Ms. LEE. Most all of that is probably because of Pap screening

and you identify the pre-cancerous condition. It is easily treated in

almost all instances. You cure it and then the woman never develops cervical cancer, and therefore, then she doesn’t get counted as

a cancer statistic. And she doesn’t have it, either.

Mr. TOWNS. Are the new treatment methods for cervical cancer

considered experimental, or are the likely to be widely accepted by

the insurance companies as a new standard of treatment?

Mr. TRIMBLE. There have now been five studies, of which three

have been published in the medical literature. We think that they

will be considered as standard of care, and insurance companies

will reimburse for their use.

Mr. TOWNS. Any other comments on that from anybody else?

[No response.]

Have we solved the lab certification issue or do we need to promote something comparable to the mammography quality standards act for Pap smears?

Ms. LEE. I am not sure any of us are really up on that. I think

that the CLIA Act—I can’t even come up with what that acronym,

Clinical Laboratory—oh, yes, you know that; thank you. It was designed—and I’m not very much up on this—but it was designed, as

one of the motivating reasons for its passage back, I think last decade, was because of problems with Pap screening; and whether is

solved it or not, I am not equipped to tell.

Mr. TOWNS. Well, let me just say, first of all, Mr. Chairman,

thank you very much and let me thank all of you for your testimony. I am sorry I was not here when you actually testified, but

I did read almost all the testimonies; I want you to know that, and

I do plan to read all of them. I was involved in another meeting

is the reason I was not here; because I am very interested in this.

You know, I come from a family of four and I lost my entire family,

except myself, from cancer. So, I’m always very interested in terms

of learning as much about this as I possibly can. I lost my mother,

father, and a brother from this disease. So I am very interested in

what you have to say.
81

So I will be reading all the material, and I really appreciate the

time and the effort you have taken to come here to share with us,

as well. Thank you so much.

Mr. COBURN. The gentleman yields back.

I have two things. Dr. Lee, would you note for the record when

we asked you a question, cancer, under the definition of those

cases, does that include carcinoma in situ or not? In terms of the

incidents that you all are quoting, is that quoting including carcinoma in situ as well as invasive cancers?

Ms. LEE. From our program, you mean?

Mr. COBURN. Yes.

Ms. LEE. No.

Mr. COBURN. It is invasive cancer only?

Ms. LEE. The 508 are invasive only, and the carcinoma in situ’s

are actually folded in with the CIN-3’s.

Mr. COBURN. All right. The other question I would ask, if you

would, in response to Mr. Towns’ question, the new epidemiological

data that I am seeing is saying that the cancer now is occurring

in earlier and earlier and younger and younger women. And, in answer to his question, your response was it is actually in older

women. Would you mind forwarding any new material that you

have to this committee, in terms of trends, epidemiologically?

Ms. LEE. Sure.

Mr. COBURN. The friends I have across the country that are practicing medicine, what they are seeing and what they are saying is

that this is a disease that is moving to young women.

Ms. LEE. Actually, what I said was the cervical cancer deaths are

highest in the older women. In fact, the people from the NCI collect

the good data on this, and we have looked at it quite a bit. The

rate of cervical cancer among women under 50, the new diagnoses

are actually going down. I looked at it the other day. They are

going down, based on seer data.

Mr. COBURN. Okay. Thank you very much. We have one additional question.

Mr. BROWN. I’m sorry to keep you here for the rest of the

evening, but, Dr. Lee, you in your testimony mention approximately half the inaccuracies—you said that the Pap test is far from

100 percent accurate; approximately half of the inadequacies are

due to an inadequate collection of the Pap smear by the provider,

and the other half are due to errors at the laboratory. And I know

your expertise is not centered around this, but does it make sense

for us to pursue perhaps the MQSA model, where there is inspection once a year, except for those who have a record of doing very,

very well, inspection of facilities once a year? I don’t know if inspection is the key, or working with, actually re-training of the people regularly, the technicians, all of that, re-licensing, some of the

things that MQSA does. Is that something we should consider

here?

Ms. LEE. That’s really something that I am not totally expert in.

I will tell you this: that the majority—and some people might even

call the substantial majority—70 to 80 percent of all new cervical

cancer cases occur in women who have not been screened in the

last 5 years. The issue: There are lab errors, and Ms. Piker was

one of those unfortunate people. There are lab errors, but that is
82

not where the bulk of the problem is. And so I will put to you that

I think, until we have something wonderful like an HPV vaccine,

that we can use to prevent, or other therapies, that our biggest, the

most important thing is to continue to go out and try to find

women who aren’t being screened. Because if we spend a lot of time

trying to improve the collection, we are still going to only maybe

be affecting up to 20 percent, and not the other 80 percent.

Mr. VALDISERRI. To comment on that, there is a part of CDC that

deals specifically with these issues, our Public Health Practice Program Office, and when we go back I will talk to their Division of

Laboratory Systems—they have been involved in the implementation of CLIA—and see if they have any specific information, both

related to what Mr. Towns asked and what you have asked. There

may be some data; we just don’t have it at our fingertips. It does

make the point, though, that you always need to remember provider education, even when you get all these other issues taken

care of.

Mr. COBURN. Let me thank the panel again for being here and

persisting with us. I appreciate your input.

I would just make one last comment, Dr. Valdiserri: that the providers in this country are way behind where they need to be in

terms of diagnosing STDs. We need to have a good national effort

to bring them back up. And thank you again.

We will bring forward the third and final panel, and I wish to

apologize for the length of your wait. Dr. John Thomas Cox from

the University of California in Santa Barbara California, and Dr.

Sharyn Lenhart, and Rosemarie Gatshca—I like that name—that’s

great—from the American Society of Clinical Pathologists.

Dr. Cox, if you would care to start and, if you could, be as brief

as possible with your testimony, so we can spend as much time as

we can discussing it.

STATEMENTS OF JOHN THOMAS COX, STUDENT HEALTH

SERVICES, UNIVERSITY OF CALIFORNIA AT SANTA BARBARA; SHARYN LENHART, IMMEDIATE PAST PRESIDENT,

AMERICAN MEDICAL WOMEN’S ASSOCIATION: AND ROSEMARIE GATSCHA, CYTOLOGY MANAGER, AMERICAN SOCIETY

OF CLINICAL PATHOLOGISTS

Mr. COX. Chairman Bilirakis, Dr. Coburn, members of the House

Subcommittee on Health and the Environment, my name is John

Thomas Cox, and I am director of the Women’s Clinic, University

of Southern California in Santa Barbara, Chair of the steering committee of the National Cancer Institute-sponsored ASCUS LSIL

trial, also known as ALTS, and Chair of the Practice Guidelines

Committee of the American Society of Colposcopy and Cervical Pathology.

I wanted to express my thanks to you for providing me the opportunity to present a clinical perspective on the issues related to

women and cervical health as I see it in 1999. In the interest of

time, the following comments are a markedly shortened version of

my written statement, and I will not be discussing the many

positives of the Pap smear screening program, as has already been

mentioned here today. But I do want to mention some of the factors
83

that we run into as clinicians, and I know, Dr. Coburn, you run

into them as well.

Despite the positives of the Pap screening program, the following

problems loom large: that while the majority of cervical cancer develops in the segment of the population that remains unscreened,

approximately 6,000 women develop cervical cancer annually, who

have had reasonable, if not all perfect, Pap smear screening. And,

although the incidence of cervical cancer and associated mortality

has decreased over 40 percent since 1973, these numbers have remained constant for over a decade. Additionally, since 1986, there

has been an annual 3 percent increase in the incidence of invasive

cervical cancer in white women under the age of 50. And now, this

is the first information I have had that that has now ceased to increase.

The risk of missing disease in the screened population is attributed primarily to false negative cytology. The false negative rate of

the Pap has been variously estimated to be from 2 to 50 percent.

However, the Agency for Health Care Policy Research just released

the evidence report, technology assessment entitled, ‘‘Evaluation of

Cervical Cytology,’’ which estimated the true sensitivity of the Pap

to be just 0.51. Their conclusion was that, ‘‘Despite the demonstrated ability of the cervical cytologic screening in reducing cervical cancer mortality, the conventional Pap test is less sensitive

that it is generally believed to be.’’ Because of the concern over the

risk of missing disease, the medical community has responded by

pursuing the diagnosis and followup of the most minimal cellular

atypia on the pap. The resulting loss in specificity brings exceptional numbers of normal women in for further evaluation. The cost

in dollars and distress of evaluation of approximately 2 million

women given the borderline reading of ASCUS has been very high.

The result is an excessively expensive, approximately $6 billion,

screening program fraught with the risk of over-diagnosis, overtreatment, and increased psychological burden.

So, I think we need to work on solutions. First, of course, we

need to start with education, which we have talked a great deal

about today. Education and outreach, especially to populations particularly reluctant to attend screening clinics, must be placed at

highest priority, since the failure to draw the unscreened portion

of the population in for routine Pap smears remains the most common reason for development of cervical cancer. The nature of failure of women to get adequate screening is not well understood, and

is likely to be the result of a complex milieu of cultural, societal,

and educational factors. Intense efforts will be necessary to understand the reasons women do not get Pap smears, or do not return,

as directed, for followup.

Additionally, women receiving cervical screening should be educated about the ideology of cervical cancer and the reasons for

doing Pap smears, including the association with HPV. Education

must extend to the healthcare providers as well, as outreach is

doomed to failure without a well-informed and empathetic health

services sector.

Second, we need a more efficient screening system, and there will

be some controversy over this, but I think we need to talk about

it. The limitations of cervical cytology in the screening system re-
84

quires a reappraisal, with the following deserving our utmost attention. We need to ask whether beginning screening at age 18, as

now recommended, is the best way to spend our cervical cancer

screen resources, since this is an age in which cervical cancer is

virtually non-existent, but transient HPV manifestations are very

common.

Additionally, the inability of caregivers to accurately predict

which women are low risk continues to foster annual screening. We

will never be able reduce the cost of the screening system until we

can safely increase the screening interval. In order to safely increase the screening interval, we will need to reduce the risk of

missed disease. New technologies have been developed to improve

the sensitivity and efficiency of detection of cervical disease. These

include liquid-based thin layer cytology, automated computerized

analyzers, and tests for the presence of HPV. Despite increasing

evidence that many of these new technologies are already improving the effectiveness of cervical cancer screening, or hold great

promise in the future, availability of the patient has been severely

eliminated.

In order to improve the efficiency of the system, we must find the

most efficient and patient acceptable manner of evaluating ASCUS

paps. The NCI ALTS study is designed to provide a clear understanding of the advantages and disadvantages of various options

for the followup of women given the Pap reading of ASCUS or LSIL

low-grade squamous intraepithial lesion. This study should settle

the question once and for all, whether women given this Pap reading are best referred immediately to colposcopy, best followed by

several repeat paps at accelerated intervals, or best tested for HPV

and referred to colposcopy only if the HPV test is positive.

Finally, the present intense public interest in healthcare quality

issues includes questions regarding who should make decisions

about how effective cervical cancer screening will be, and by what

measure should effectiveness be evaluated. Until now, new cervical

screening technology assessments, which have influenced public

policy, have focused almost entirely on the single end-point of costeffectiveness as measured by cancers prevented and lives saved.

In contrast, women deserve that cervical cancer screening policy

be set by a much fairer model, that encompasses quality-of-life

issues associated with decreasing the ambiguity of equivocal paps

and with earlier detection of disease. This would include reproductive implications and reductions in invasive treatments, patient

anxiety, and loss of time from work and childcare.

We must acknowledge the individual patient’s interest in receiving information about the benefits, risks and costs of traditional

Pap followup compared with new cytology screening enhancements.

Women have a right to be routinely informed of these issues and

to participate in decisionmaking regarding their health choices.

And, thank you for the opportunity to address these issues, and

I will be pleased to answer any questions that you may have.

[The prepared statement of J. Thomas Cox follows:]

PREPARED STATEMENT OF J. THOMAS COX, DIRECTOR, WOMEN’S CLINIC, UNIVERSITY

OF CALIFORNIA, SANTA BARBARA

Chairman Bilirakis, members of the House Subcommittee on Health and the Environment, my name is John Thomas Cox, MD. I am Director of the Women’s Clinic
85

at the University of California in Santa Barbara, Chair of the Steering Committee

for the National Cancer Institute sponsored ASCUS/LSIL Triage Study (ALTS) and

Chair of the Practice Guidelines Committee of the American Society of Colposcopy

and Cervical Pathology. I want to express my thanks for providing me the opportunity to present a clinical perspective on the issues related to women and cervical

health as I see it in 1999.

The Positives of Cervical Cancer Screening

In countries without cervical cancer screening, cervical cancer remains first or second amongst all cancers in women in both incidence and mortality. The measure

of success of the Pap smear screening program in countries fortunate enough to

have such a program, such as the US, is relegation of cervical cancer to the 6th commonest cancer amongst women and the 10th leading cause of cancer death. These

decreases in the US are so dramatic that Pap smear screening is one of the few

interventions to receive an ‘‘A’’ recommendation from the U.S. Preventive Services

Task Force even though there have been no randomized trials demonstrating its effectiveness.

Problems with the Cervical Cancer Screening Program

Approximately 14,000 women develop cervical cancer in the US annually and approximately 5000 die of the disease. While the majority of cervical cancer develops

in the segment of the population that remains unscreened, approximately 6000

women develop cervical cancer annually who have had reasonable, if not all perfect,

Pap smear screening. The lifetime likelihood that a women never screened will develop cervical cancer is 3,748 women per 100,000 (3.7%), but even with annual

screening approximately 305 per 100,000 women (0.3%) will develop cervical cancer

during their life. Although this dramatic drop in incidence demonstrates the remarkable effectiveness of the Pap screening program, nevertheless this is a toll that

is individually agonizing for both patient and for care-giver. Even though the incidence of cervical cancer and associated mortality have each decreased over 40%

since 1973, these numbers have remained fairly constant for over a decade. Additionally, since 1986 there has been an annual 3% increase in the incidence of

invasive cervical cancer in young white women under the age of 50.

These statistics highlight both the success of cervical cytologic screening and the

fact that, like any other test, achievement will never reach a perfect score. The risk

of missing disease in the screened population is attributed primarily to false-negative cytology. The false-negative rate of the Pap has been variously estimated to be

from 2% to greater than 50%. In January, 1999 the Agency for Health Care Policy

and Research (AHCPR) released the Evidence Report/Technology Assessment, ‘‘Evaluation of Cervical Cytology’’. Using a stringent meta-analysis of published studies

comparing cervical cytologic diagnosis with clinical diagnosis based on colposcopy or

biopsy, the AHCPR provided an estimate of the true sensitivity of the Pap to be

0.51. Their conclusion was that ‘‘despite the demonstrated ability of cervical

cytologic screening in reducing cervical cancer mortality, the conventional Pap test

is less sensitive than it is generally believed to be’’.

Such statistics are in direct conflict with the public perception that the Pap smear

is, or should be, an infallible test. The result in failed expectations is exceptional

medicolegal liability related to the development of cervical cancer in any women

with a history of previous cervical screening. For this reason, failure to diagnose cervical cancer is the second leading cause of liability losses for gynecologists and the

leading liability for laboratories even though revenue from cytology accounts for only

a small fraction of total laboratory income.

While false-negative cytology accounts for the majority of failures in the screened

population, the poor specificity of cytology may be a greater problem for both the

individual and society. The low rate of cervical cancer makes the risk of missing disease statistically small for each individual patient and for each Pap. However, the

reality of the imperfect nature of the test looms large for both the laboratory personnel reading the Pap and for the caregiver. When the threshold for evaluation of

a woman with an abnormal Pap is set very high, i.e. a high-grade or HSIL Pap,

the specificity of the Pap is very good. That means that disease with significant

threat to the woman is likely to be found on further evaluation. However, in order

to protect our patients and ourselves from the vicissitudes of missed cervical cancer,

the medical community has responded by pursuit of even the most minimally atypical cells. When the threshold for evaluating women with an abnormal Pap is set

low, specificity falls dramatically. This means that many normal women will be

evaluated for minimally abnormal Paps. The result is an excessively expensive (6

billion dollar) screening program fraught with the risk of overdiagnosis, overtreatment, and increased psychological burden. While all who have taken the Hippocratic

Oath de-
86

sire to do anything and everything possible to prevent an untimely loss of life, we

must admit that much of our response to minor cytologic abnormalities has developed less out of reason than out of fear of liability.

Solutions

How can we penetrate this impasse in the further reduction in cervical cancer incidence and mortality? Will attempts to further reduce the rate of cervical cancer

make the system unaffordable? Should we ‘‘tinker’’ with the present system or is

there reason, or promise, to justify a major re-evaluation of how we approach cervical cytologic screening and follow-up to abnormal Pap smears? How can we motivate the unscreened population to obtain good cervical health care? I believe that

the answers to these questions can be found by vigorous pursuit of the following:

Education

Education and outreach, especially to populations particularly reluctant to attend

screening clinics must be placed at highest priority since the failure to draw the

unscreened portion of the population in for routine Pap smears remains the most

common reason for development of cervical cancer. While financial barriers are often

cited as a major reason in limiting access to cervical screening, most studies have

concluded that cost plays a minor, almost insignificant role. For example, Canadians, for whom all health care coverage is provided, have non-compliance patterns

nearly identical with those of patients in the United States. Additionally, approximately 60% of women getting cervical cancer in one of the largest prepaid HMOs

in the U.S. had not received adequate Pap smear screening even though a large percentage of these women had seen their primary care physician in the recent past.

These statistics highlight the complex nature of failure of women to get adequate

screening, which is likely to be the result of a complex milieu of cultural, societal

and educational factors. Education must extend not only to women in the

unscreened population, but women already being screened and to their caregivers.

Intense efforts will be needed to understand the reasons for failure to attend screening and to apply the resources necessary to overcome these barriers.

Additionally, women receiving cervical screening should be educated about the etiology of cervical cancer. In 1995 the Agency for Research in Cancer and the World

Health Organization (WHO) proclaimed cervical cancer to be the virtually exclusive

result of the long-term persistence of human papillomavirus (HPV). Education must

extend to health care providers as well, as outreach is doomed to failure without

a well-informed and empathetic health services sector. Women must be made aware

of the etiology of cervical cancer and its precursors, and, thereby, of the reason for

which Pap smear screening is performed. Discussion of the sexually transmitted nature of the process cannot be avoided. However, it must be done without prejudice

and with great care, compassion, and reassurance given that although the virus is

extremely common, the risk for the development of cervical cancer is very low, especially with conscientious Pap smear screening. Clinicians must be continually reminded of the importance of cervical cancer screening so that women attending for

medical care for other reasons may yet obtain a Pap smear in what may be their

only encounter with the medical community.

A More Efficient Screening System

Taking a new look at what is generally considered to be a successful system is

never without controversy. However, the limitations of cervical cytology and the

screening system requires a reappraisal, with the following deserving our utmost attention.

1). Optimal age to begin screening and optimal screening interval: The pattern of

practice in cervical cancer screening has been largely unchanged for 50 years. Annual Paps beginning at age 18 or within one year of beginning sexual activity,

whichever comes first, remains the standard of care even though ACS and ACOG

guidelines provide the option to extend the screening interval to 3 years in women

considered at low risk. Concerns regarding false-negative cytology, medicolegal liability and the improbability of being able to accurately predict which women are

really at low risk has served as the major impediment to implementation of prolonged screening intervals. Additionally, due to the high-prevalence of HPV and its

induced cytologic changes in young women, a significant portion of the funds available for cervical cancer screening are spent on diagnosis and treatment of a commonly transient manifestation at little to no immediate risk of cervical cancer, and

low long-term risk. While it is very important to test for sexually transmitted diseases (STDs) in this age group, the peculiar characteristics of HPV may not make

Pap screening in very young women the most prudent approach.

In order to provide the safest, yet still cost-efficient coverage, we must consider

redirecting the greatest concentration of our cervical cancer screening resources to
87

those populations at greatest risk and least likely to be traumatized unnecessarily

by medical intervention. This may require beginning screening at a somewhat later

age and extending the screening interval. However, safely extending the screening

interval would require greater reassurance than that provided by a screening test

with just over 0 .50 sensitivity.

2). Reducing the risk of missed disease: New technologies have been developed to

improve the sensitivity and efficiency of detection of cervical disease. These include

liquid-based thin-layer cytology, automated computerized analyzers, and tests for

the presence of HPV. False negative Paps are generally very difficult Paps to read,

often with very few abnormal cells, and often compromised by obscuring inflammation, blood or other exudate. Liquid-based cytology eliminates much of the potential

for obscured Paps and may provide a more representative sample. Computer analyzers have been approved for both primary review of the Pap and for CLIA mandated rescreening. HPV testing as an adjunct to the Pap smear in women over the

age of 30, who are less likely to be positive for HPV in the absence of cervical disease, would appear to increase the negative predictive value of the screen to approximately 97% without flooding the system with normal women. Yet, despite increasing evidence that many of these new technologies are already improving the

effectiveness of cervical cancer screening, or hold great promise in the near future,

availability to the patient has been severely limited. The reasons for this are quite

clear. In the present managed care environment it is not sufficient to prove increased efficacy. Increasingly, the interests of third-party payers have dictated the

interaction between clinician and patient. There is now the opportunity to make a

significant impact on both the loss of life and on the inefficiency of the cervical cytology screening program if we have the will and the foresight to integrate the best

that these technologies provide. If we do not, the present impasse in further reduction in cervical cancer will remain, and the commercial viability and future availability of these major improvements will be lost. Much not only depends upon the

willingness of third-party payers to cover appropriately effective emerging technologies, but also upon a full understanding by clinicians of their potential and the

willingness to discuss the new methods with their patients.

3). Providing the most objective and efficient triage of women with equivocal Paps:

The NCI/ALTS Study is designed to provide a clear understanding of the advantages and disadvantages of various options for the follow-up of women given the

equivocal Pap smear reading of atypical squamous cells of undetermined significance (ASCUS) and the more diagnostic reading (for the probability of association

with HPV) of low grade squamous intraepithelial lesion (LSIL). The follow-up options being evaluated include a). Immediate referral to colposcopy of all women with

ASCUS or LSIL Paps, b). Repeat Pap until the woman has obtained 3 or 4 normal

follow-up Paps with referral to colposcopy if any repeat is abnormal, or 3). Testing

for the presence of HPV and referral to colposcopy only if the test is positive for

an HPV type known to be associated with high-grade cervical precancers and cancer. Until this time there has been substantial disagreement amongst the medical

community regarding which of these options is best. Recently, however, the availability in research settings of Hybrid Capture II, a new HPV test with improved

sensitivity has provided very favorable results as a triage option for ASCUS. The

comprehensive, randomized protocol of the ALTS Trial should once and for all settle

the question of which follow-up option is most reliable, most cost-efficient, and, perhaps of greatest importance, most acceptable to women.

4). Evaluating the cost-effectiveness of cervical screening options: The present intense public interest in health care quality issues includes questions regarding who

should decide how effective cervical cancer screening will be, and by what measures

should effectiveness be evaluated? Two important technology assessment reports

have recently been released; the report of the Technology Evaluation Center of the

Blue Cross and Blue Shield Association (April, 1998) and the AGOG Committee

Opinion: New Pap Screening Techniques (August, 1998). Both emphasize the group

perspective on cost-effectiveness, almost to the exclusion of, or even acknowledging

the individual patient’s interest in receiving information about the benefits, risks,

and costs of traditional Paps compared with new cytology screening enhancements.

Unfortunately, cost-containment analysis has focused only on reduction in death

from cervical cancer. Considering the already relatively low rate of cervical cancer,

this is an endpoint doomed to show insignificant changes in increased life expectancy when factored over the entire population of women screened. A much fairer

model for women is one that takes into account all the factors of cervical cancer

screening that affect their lives. This would encompass quality-of-life issues associated with earlier detection of disease, including reproductive implications, and reductions in invasive treatments, patient anxiety and loss of time from work and

childcare. In addition, cost-benefit analysis includes an evaluation of the benefits de-
88

rived for both patient and caregiver of reducing and clarifying the nature of borderline Pap readings and obscured or otherwise compromised specimens that result in

unnecessary repeat visits. Women have a right to be routinely informed of these

issues and to participate in decision-making regarding their health choices.

Again, thank you for the opportunity to address these issues. I will be pleased

to answer any questions that you may have.

Mr. COBURN. Dr. Lenhart.

STATEMENT OF SHARYN LENHART

Mr. LENHART. Thank you. Good afternoon, Mr. Chairman and

members of the subcommittee. My name is Dr. Sharyn Lenhart. I

am the immediate past president of the American Medical Women’s

Association, and I also chair AMWA’s Advisory Committee to the

National Cervical Cancer Public Education Campaign.

The American Medical Women’s Association or AMWA is a national multi-specialty organization comprised of more than 10,000

women physicians and medical students. As a leading advocate for

women’s health issues since 1915, AMWA members have advocated

for Federal legislation, influenced local policy, developed physician

education programs, and spearheaded national consumer education

campaigns to ensure that women patients and women physicians

maintain a voice in upholding the highest standards of care as they

relate to women’s health.

AMWA believes that there is an important role for the Federal

Government to play in improving women’s health. We believe that

this role can be fulfilled through Federal legislation that recognizes

the need for women to understand how they can prevent and detect

cervical cancer, and through legislation which supports adequate

coverage of cervical cancer screening technologies, treatments, and

preventative measures. Medicare reimbursement for Pap tests isn’t

adequate currently to cover the costs of providing laboratory services and should be increased to ensure the continued availability of

this primary screening device.

Each year in the United States approximately 15,000 women are

diagnosed with cervical cancer and 5,000 United States women die

of the disease. Since the introduction of the Pap test almost 50

years ago, cervical cancer rates have been reduced by 75 percent.

The majority of cervical cancers now occur in the minority of

women who are not adequately screened. Two-thirds of cervical

cancers occur in women who have not been screened and who constitute minority groups, by and large.

Despite the enormous success of the Pap smear, however, onethird of preventable cervical cancer occurs in women who have had

a Pap test, at least in the last 5 years. Because cervical cancer is

a slowly progressing cancer, often taking 10 to 15 years to develop,

regular Pap smear screening, combined with new and cutting-edge

screening tools, can lead to greater success in prevention.

The success of cervical screening is that it detects abnormal cells

which can be treated before an actual cancer develops. Recent clinical studies have confirmed that the human papillomavirus, HPV,

is the primary cause of cervical cancer. HPV is a very common

virus which can infect any man or woman who has ever had sexual

intercourse. In most cases HPV is harmless and asystematic. It is

estimated, however, that up to 80 percent of women in the United

States contract the virus at some point during their lives. Only a
89

few of these women, those with persistent HPV infection of a highrisk type, will develop cervical cancer.

Seventy types of HPV have been identified and approximately 13

of those are high-risk. The ability to identify the precedents of the

high-risk cancer groups or HPV groups may be the key in our efforts to combat this disease. Unfortunately, a recent survey confirmed that 70 percent of women are unable to name the cause of

cervical cancer. While women should receive regular Pap smear

screening, 2 million of these screenings produce borderline results,

and another 1.5 million produce abnormal results. Recent studies

have shown that as a followup to borderline Pap smear results, the

use of enhanced screening technologies, including a new test that

detects the presence or absence of the HPV, can give a woman’s

health provider added information about the cause of her borderline results. Follow-up options can then be tailored appropriately.

AMWA believes that cervical cancer can be the first major victory in the war against cancer. We believe that, in order to achieve

this victory, American women and their providers need more education about cervical cancer, the importance of regular Pap smear

screening, appropriate enhanced screening technologies, treatment

modalities, and current and cutting-edge tests for the causes of cervical cancer. As an organization of women physicians, AMWA recognizes the crucial role we play in leading the fight against this

cancer. We are more likely to provide Pap smear screening, inform

our patients about cervical cancer, and encourage routine screening.

Essentially, the battle against cervical cancer can only be won

with a twofold strategy of increasing the number of well-educated,

pro-active women consumers and enlisting the help of physicians

who encourage and provide routine screening. AMWA views the

Pap smear screening as a critical device in detecting cervical cancer. We also regard enhanced screening technologies and HPV testing, in the event of a borderline Pap smear result, to be an effective

way to provide healthcare providers with important additional information.

To this end, we have become a lead partner in the National Cervical Cancer Public Education Campaign. The Campaign is a collaborative educational effort involving representatives from leading

women’s health and civic organizations designed to inform women

about the link between HPV and cervical cancer, to reinforce the

importance of regular Pap smear screening, to introduce them to

new and existing methods to detect cervical cancer, and to empower them to take an active role in discussing the disease with

their healthcare providers. The goal of the Campaign is to reduce

the number of preventable deaths caused each year by cervical cancer through increased education and outreach.

Mr. COBURN. Dr. Lenhart, can you summarize?

Mr. LENHART. Yes. AMWA calls on Members of Congress to demonstrate their support for public education about cervical cancer by

signing on as co-sponsors of the Cervical Cancer Awareness Resolution and the Breast Cancer Treatment Act.

The key to winning the fight against cervical cancer is early detection. We can screen for it; we can test for HPV, and we can treat
90

it. No woman in this country needs die from cervical cancer. If we

all do our part, we can make this a reality. Thank you.

[The prepared statement of Sharyn Lenhart follows:]

PREPARED STATEMENT OF SHARYN LENHART, IMMEDIATE PAST PRESIDENT, AMERICAN

MEDICAL WOMEN’S ASSOCIATION

The American Medical Women’s Association (AMWA) is a national medical organization comprised of more than 10,000 women physicians and medical students. A

leading advocate for women’s health issues, AMWA is dedicated to improving the

quality of women’s healthcare. Since 1915, AMWA members have advocated for federal legislation, influenced local policy, developed physician education programs, and

spearheaded national consumer education campaigns to ensure that women patients

and women physicians maintain a voice in upholding the highest standards of care

as they relate to women’s health.

AMWA believes that there is an important role for the federal government to play

in improving women’s health. We believe this role can be fulfilled through federal

legislation that recognizes the need for women to understand how they can prevent

and detect cervical cancer and through legislation which supports adequate coverage

of cervical cancer screening technologies. Currently, Medicare reimbursement for

Pap tests is inadequate to cover the costs of providing laboratory service. Reimbursement should be increased to adequately cover costs, ensuring women have access to the most effective technology for detecting cervical cancer. The majority of

deaths from cervical cancer are unnecessary and preventable.

THE SCOPE OF THE PROBLEM

Each year in the United States, approximately 15,000 women are diagnosed with

cervical cancer and 5,000 women die of the disease. Since the introduction of the

Pap test over forty-five years ago, U.S. incidences of cervical cancer have been reduced by 75%. The majority of cervical cancers now occur in the minority of women

who are not adequately screened. Two-thirds of cervical cancers occur in women who

have not been screened. Yet despite this enormous success, one third of preventable

cervical cancer occur in women who have had a Pap smear in the last five years.

Because cervical cancer is a slowly progressing cancer, often taking ten to fifteen

years to develop, regular pap smear screening combined with new and cutting edge

screening tools can lead to greater success in prevention. The success of cervical

screening is that it detects abnormal cells which can be treated before cancer even

develops.

CERVICAL CANCER AND THE HUMAN PAPILLOMAVIRUS (HPV)

Recent clinical studies have confirmed that the human papillomavirus (HPV) is

the primary cause of cervical cancer. HPV is a very common virus which can infect

anyone who has ever had sexual intercourse. In most cases, HPV is harmless and

people never realize they have it. It is established that up to 80 percent of women

in the United States contract the virus at some point during their lives. But, only

a few of the women with HPV will develop cervical cancer. Although infection with

certain types of HPV increases the risk of cervical cancer, most infected women do

not develop cancer. In fact, of the more the 70 types of HPV, only 13 are associated

with cervical cancer. The ability to identify the presence of high risk HPV may be

the key in our efforts to combat this disease. Unfortunately, a recent survey confirmed that 70 percent of women are unable to name the cause of cervical cancer.

While women should receive regular pap smear screening, in many cases, these

screenings produce borderline results. Of the 50 million Pap smears performed in

the United States annually, 3.5 million produce abnormal results. Recent studies

have shown that as a follow-up to borderline pap smear results, the use of enhanced

screening technologies, including a new test that detects the presence or absence of

HPV, can give a woman’s healthcare provider added information about the cause of

her borderline results. Follow-up options can then be tailored appropriately.

AMWA’S PERSPECTIVE ON CERVICAL CANCER

AMWA believes cervical cancer can be the first major victory in the war against

cancer. We believe that in order to achieve this victory, American women and their

healthcare providers need more education about cervical cancer, the importance of

regular pap smear screening, enhanced screening technologies, and current and cutting edge tests for the causes of cervical cancer. As an organization of women physicians, AMWA recognizes the crucial role we play in leading the fight against this
91

cancer. We are more likely to provide pap smear screening, inform their patients

about cervical cancer, and encourage routine screening. Essentially, the battle

against cervical cancer can only be won with the two-fold strategy of increasing the

number of well-educated, proactive women consumers and enlisting the help of physicians who encourage routine screening. AMWA views regular pap smear screening

as critical in detecting cervical cancer. We also regard HPV testing, in the event of

a borderline pap smear result, to be an effective way to provide healthcare providers

with important additional information. To this end, we have become the lead partner in the National Cervical Cancer Public Education Campaign. The Campaign is

a collaborative, educational effort involving representatives from leading women’s

health and civic organizations designed to inform women about the link between

HPV and cervical cancer, reinforce the importance of regular pap smear screening,

introduce new and existing methods to detect cervical cancer, and empower them

to take an active role in discussing the disease with their healthcare providers. The

goal of the Campaign is to reduce the number of preventable deaths caused each

year by cervical cancer through increased education and outreach.

CONCLUSION

AMWA calls on Members of Congress to demonstrate their support for public education about cervical cancer by signing on as cosponsors of the Cervical Cancer

Awareness Resolution that has been introduced by Representatives MillenderMcDonald, Lazio and Coburn. The key to winning the fight against cervical cancer

is early detection. We can screen for it, we can test for HPV, and we can treat it.

No woman in this country need die from cervical cancer. If we all do our part, we

can make this a reality.

Mr. COBURN. Thank you, Dr. Lenhart.

Ms. Gatscha, please.

STATEMENT OF ROSEMARIE GATSCHA

Ms. GATSCHA. Mr. Chairman, members of the subcommittee, on

behalf of the American Society of Clinical Pathologists, I would like

to thank you for inviting me to speak here today. My name is Rosemarie Gatscha, and I am the Cytology Manager at Memorial Sloan

Kettering Cancer Center in New York City. I am here representing

the ASCP, which is the largest medical laboratory organization in

the world. ASCP represents 75,000 members, including board-certified pathologists, clinical scientists, and certified technologists

and technicians.

I would like to take a moment to explain what I do as a cytotechnologist. Cells are collected from a woman’s uterine cervix,

placed on a smear, sent to the laboratory for processing and evaluation. Part of my job is processing. Most of my job is evaluating

these Pap smears.

As you can see here, this gives you an example of some cells that

are present on a smear. These cells, in particular, are cancer cells

from cervical cancer. It gives you a feeling for the numbers of cells

that are present on this smear. It varies anywhere from 30,000 to

200,000 cells. It is important that a well-trained eye be reviewing

these cells, and that is what a cyto-technologist does, discriminates

between normal and abnormal cells.

While it is difficult to believe more women die of cervical cancer

because they have never had a Pap smear or because they haven’t

had a Pap smear in the last 5 years than those that die of a false

negative Pap smear, there are many reasons why some women do

not have Pap smears and there are reasons why they are less

available to some women. Let’s look at availability first.

ASCP’s Board of Registry, in conjunction with MORPACE International, based in Detroit, conducts the biennial wage and vacancy
92

survey of 2,500 medical laboratory supervisors. The 1998 data was

just made available, and the information regarding cyto-technologists is of particular concern. The current vacancy rate for cytotechnologists working at the staff level is 10.5 percent. This is a 3

percent increase over the 1996 rate, which was 7 percent. This is

the first increase in the cyto-technologist staff level vacancy rate in

the last 8 years. What is critical to note is that the vacancy rate

in rural areas is 17.6 percent. While the overall vacancy rate for

supervisors, cyto-technology supervisors, has decreased slightly

over the past 2 years, the vacancy rate in small medium-sized cities is increasing. It is 20 percent.

These data show some cause for concern, and I realize that sometimes numbers of this type may be meaningless, but to put it in

perspective, you may recall the nursing shortage crisis. At the

height of their crisis, the shortage was 11.3 percent.

Cyto-technologists are highly skilled and trained individuals.

Laboratories rely on certified cyto-technologists to evaluate Pap

smears. With high vacancy rates, there is concern that some laboratories will not have the appropriate personnel available to

evaluate those Pap smears. This leads me to a related issue.

Cyto-pathology smears are currently priced at $7.15 on the Medicare laboratory fee schedule. The actual cost of the conventional

Pap smear is between $13 and $17. This price includes cyto-technologists’ salaries, overhead costs, CLIA-mandated quality control,

and laboratory supplies, and also supplies that are given to

healthcare providers who obtain the Pap smear. The Medicare payment rate for Pap smears should increase significantly. This, in

turn, will help to alleviate the personnel shortages that exist which

are amongst our most serious concerns.

Despite increased publicity and a greater emphasis on cervical

cancer screening, a lack of knowledge continues to be a barrier to

women in obtaining a Pap smear. A woman is more likely to obtain

a smear if symptoms are present and if there is social pressure on

her to do so. Barriers to obtaining a smear also include fear and

embarrassment, belief that Pap smears are unnecessary for older

women, economic factors, and language and cultural barriers.

We look forward to continuing to work with you on the prevention of cervical cancer by increasing the availability of trained cytotechnologists, increasing Medicare reimbursement for Pap smear

testing, and minimizing economic and cultural factors that stop

women from having Pap smears. Thank you very much for your attention. If there are any questions, I would be pleased to answer

them.

[The prepared statement of Rosemarie Gatscha follows:]

PREPARED STATEMENT OF ROSE MARIE GATSCHA, AMERICAN SOCIETY OF CLINICAL

PATHOLOGISTS

Chairman Bilirakis, members of the subcommittee, my name is Rose Marie

Gatscha, SCT(ASCP). I am Cytology Manager at Memorial Sloan-Kettering Cancer

Center in New York City. I am here today representing the American Society of

Clinical Pathologists.

The American Society of Clinical Pathologists (ASCP) is a nonprofit medical specialty society organized for educational and scientific purposes. Its 75,000 members

include board certified pathologists, other physicians, clinical scientists, and certified technologists and technicians. These professionals recognize the Society as the

principal source of continuing education in pathology and as the leading organiza-
93

tion for the certification of laboratory personnel. ASCP’s certifying board registers

more than 150,000 laboratory professionals annually.

THE PAP SMEAR FACTS

The Pap smear is a proven screening method of detecting and preventing cervical

cancer. It is the most effective cancer screening test in medical history as it is largely responsible for the 70% to 80% decline in death due to cervical cancer over the

last 50 years in the United States.

Approximately 4,900 women die from cervical cancer annually in this country,

making it the tenth leading cause of death from cancer in women. Approximately

14,000 new cases of cervical cancer are diagnosed each year.

The Pap smear is a safe, noninvasive, cost-effective medical procedure. Cells collected from a woman’s uterine cervix are sent to a cytopathology laboratory where

the cells are evaluated. The cytotechnologist prepares the slide and evaluates the

specimen, which is composed of thousands of cells—usually between 30,000 to

200,000 cells in a single specimen. If the specimen is within normal limits, a report

is sent to the woman’s health care provider. If an abnormality is detected, then a

pathologist examines the slide and issues a final diagnosis.

BARRIERS TO PAP SMEAR TESTING

While it is difficult to believe, more women (80%) die of cervical cancer because

they have never had a Pap smear or they have not had a Pap smear in the last

five years than those that die of a false negative Pap smear. We believe this is unconscionable.

There are many reasons why some women do not have Pap smears, or why Pap

smears may be less available to women. I’d like to devote the rest of my comments

to exploring those reasons.

Trained Cytotechnologists Are Needed

The American Society of Clinical Pathologists’ Board of Registry, in conjunction

with MORPACE International, Detroit, conducts a biennial wage and vacancy survey of 2,500 medical laboratory managers. The survey measures the vacancy rates

for 10 medical laboratory positions, and compares and contrasts these data with

that from 1988, 1990, 1992, 1994, and 1996 studies. The 1998 data has just been

made available, and the information regarding cytotechnologists, the professionals

who interpret cellular material such as Pap smears, is of particular interest and

concern.

The current vacancy rate for cytotechnologists (staff level) is 10.5%, an increase

over the 1996 rate, which was 7.1%. This is the first increase in the cytotechnologist

(staff level) vacancy rate in eight years. It is also important to note that for rural

areas, the cytotechnologist (staff level) vacancy rate is 17.6%, and totals 9.7% for

small-medium size cities and 12.1% in large cities. Also, while the vacancy rate for

cytotechnologist (staff level) in large hospitals is 8.3%, the vacancy rate nearly doubles for hospitals with a 100-299 bed size—up to 15.8%. Hospitals with bed size of

300-499 reported vacancy rates for these professionals at 14.3%.

Laboratory managers were questioned about the difficulty they have in filling

work shifts. 21% reported problems recruiting cytotechnologist (staff level) for day

shifts, three times higher than the 8% reporting such difficulties in 1996.

While the overall vacancy rate for cytotechnologist (supervisor) has decreased over

the past two years, 10% down from 12.5%, the vacancy rate in small-medium size

cities for cytotechnologist (supervisor) is 20.0%. Vacancy rates for cytotechnologist

(supervisor), while virtually non-existent in the east north central, west south central, and far west regions of the country, are explosive in the northeast (16.7%),

south central atlantic (18.2%), and west north central (12.5%) parts of the nation.

These data show some cause for concern. Cytotechnologists are highly skilled and

trained individuals, who must have at least a baccalaureate degree followed by a

year of specialized training in cytology. Cytotechnologists must then take a rigorous

national certifying examination, administered by the ASCP, in order to become certified. Laboratories rely on certified cytotechnologists to evaluate all Pap smears.

With high vacancy rates, there is concern that some laboratories will not have the

appropriate personnel available to evaluate Pap smears.

Medicare Reimbursement

Cytopathology smears are currently priced at $7.15 on the Medicare laboratory fee

schedule. The actual cost of the conventional Pap smear (excluding new technology

and the professional component for physicians) is in the range of $13 to $17. The

cost of new liquid-based Pap testing is $28-$32. This price includes cytotechnologist
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salaries, overhead costs, CLIA-mandated quality control, laboratory supplies, and

supplies given to healthcare providers who obtain the smear. The Medicare payment

rate for Pap smears should increase significantly.

ASCP and other organizations are working with the Health Care Financing Administration to increase the Medicare payment rate for Pap smears. In addition,

Representative Neil Abercrombie and Representative Mary Bono have recently

sponsored legislation, HR 976, to increase the Medicare payment rate to $14.60.

ASCP supports this effort to bring attention to the need for the Pap test and a more

appropriate payment rate.

Liability

With annual screening, the chance of a woman developing cervical cancer can be

reduced to less than 1%. Pap smears have an irreducible false negative rate (10%-

40%) due to sampling errors on the part of health care providers and screening errors occurring in laboratories.

According to a March 1997 report in the Archives of Pathology and Laboratory

Medicine, the continued availability of Pap cancer screening test is threatened by

lawsuits because the legal system demands a zero error rate which is mathematically unachievable even in the most competent professional hands.

Socioeconomic Barriers

According to Healthy People 2000, the National Health Promotion and Disease

Prevention Objectives, there are several key assumptions that may be used to help

overcome barriers to cervical cancer screening. The objectives state, ‘‘low income,

low education and advancing age are all associated with a decreased likelihood of

receiving Pap tests.’’ The report continues that ‘‘age influences both cervical cancer

incidence and survival. While younger women are more frequently diagnosed with

cervical cancer, older women are more often diagnosed at later stages of the disease

and are more likely to die from it than younger women.’’ We are also aware that

certain populations of women—African American, Hispanic, Asian, and low-income

rural women—often face cultural and economic barriers to Pap screening.

For example, it is not uncommon for low-income women of Hispanic descent to

refuse Pap testing. Even if the Pap smear is free or of little cost, these women,

whose families may rely on them for income and support, refuse the test because

they do not want to know if they have cancer. A cancer diagnosis, in this instance,

would mean extensive, and often prohibitive, medical costs to treat the cancer, and

would tear the women away from their families for extended periods of time. Many

women in this situation prefer not to know their potential cancer status. In addition, a lack of culturally appropriate materials or information communicated in

Spanish is a barrier to Hispanic women being screened.

In a study compiled by the Centers for Disease and Prevention, it was determined

that transportation and its costs were barriers to Pap testing for Native American

women. In speaking with public health officials, we are also aware of examples in certain

Asian-American communities where it is considered shameful for women to have a

Pap smear. In this culture, husbands may not want their wives to be examined ‘‘in

that way’’ by a male physician.

SOLUTIONS

The Pap smear, named for its creator Dr. George N. Papanicolaou, is one of the

most effective cancer screening tools available to women today. There are ways to

lessen the barriers that exist to Pap testing, so that cervical cancer becomes a less

formidable disease to women.

ASCP continues to work with the cytology community to provide continuing education and certification for these laboratory professionals. ASCP has also established

a scholarship program for medical technology students, including cytotechnologists.

The Society awards 100 student scholarships each year to assist with educational

finances.

Last year, your Committee reauthorized Title VII of the Public Health Service Act

(Health Professions Education Partnerships Act of 1998, P.L. 105-392), which included a program for Allied Health Project Grants. This program has been effective

in addressing the training and educational needs of allied health personnel, including cytotechnologists. However, further strides in funding are still needed to increase the number of cytotechnologists to an adequate level.

Increasing the Medicare reimbursement for Pap testing to an amount more in line

with current costs would also help to attract and retain professionals in the field.

ASCP, along with many other organizations, are working to educate the general

public and the priority populations mentioned above about the importance and effec-
95

tiveness of the Pap smear. We are particularly proud of the efforts we have undertaken to help educate other health care providers about the Pap smear.

ASCP believes it is important to develop and disseminate educational materials

to targetted populations and to the health care providers that serve them, and develop relationships with community organizations, such as schools, retailers, employers, social facilities, and churches, to assist in reaching women that are not participating in cervical cancer screening programs.

We aim to continue these educational efforts, and look forward to working with

you and others in the prevention of cervical cancer.

I would be pleased to answer any questions you may have.

Mr. COBURN. Thank you, Ms. Gatscha.

I am going to take the first round of questions, if I may. Dr. Cox,

would you tell us a little more about the ALTS study and what you

hope to come out of that, and the implications for us in terms of

health policy?

Mr. COX. Yes, I would be very happy to. As you know, the 1988

Bethesda guidelines created a new category called ASCUS. And

ASCUS, as an OB-GYN, you know has been probably the hardest

Pap smear reading for us to deal with. That is why many people

say, ‘‘Don’t ASCUS,’’ because it is an equivocal pap. The problem

with it is that it is the most common Pap smear reading that is

considered abnormal. It is the least risky in terms of the percentage of those with ASCUS that have high-grade disease. About 6 to

8 percent will have high grade disease. However, the total highgrade disease discovered by Pap smear in the United States, about

30 to 40 percent of it comes from ASCUS. A great deal of cancer

comes from under that Pap smear reading as well. So, it is our biggest problem, because most people are normal, but there is this

hidden sort of group underneath that are very, very risky.

So the ASCUS LSIL trial was set up to evaluate whether it is

best to refer women immediately to colposcopy, which is looking at

the cervix with a microscope on the stand in the doctor’s office,

whether it is better to do that immediately, whether it is better to

follow ASCUS by repeating the Pap 3 or 4 times, and if any repeat

Pap is abnormal, then colposcopy in those women, and if they are

not abnormal, sending them back to annual exams; or whether it

is better to test for the causing by bringing the woman back in and

doing an HPV test on followup; and colposcopy in those women

high-risk positive and returning the women that are not a highrisk positive either to a Pap in 6 months and then annual exams,

or maybe immediately to Pap smear annually. So the ASCUS LSIL

trial was specifically set up to determine which triage is most costeffective, which detects the most high-grade disease, which is most

patient-acceptable, as a very extensive ongoing patient questionnaire to see what kinds of issues and anxieties are involved with

each office visit, et cetera, so that we get some kind of an idea what

women want to do the most.

Mr. COBURN. You mentioned, can you explain for the rest of the

panel a little bit, about what the new thin-prep is and how it works

and why it is reported to help us in terms of diagnostic criteria?

Mr. COX. In 1996, the FDA approved thin-prep paps, and they

are, I believe, going to be soon approving a liquid-based Pap for

Roche as well called CytoRich. These are Pap smears in which the

sample is taken from the cervix in the same manner as for a glass

slide pap, which is a conventional pap. But instead of putting the

swab in, or with a collection device immediately on, a slide is put
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into a liquid media. In terms of the thin-prep pap, that liquid

media is sent to the cyto-pathology laboratory. A cylinder is put in

the liquid media and spun to disperse the cells. The cells are

sucked into a filter, and when about 70,000 cells hits that filter

enough, a vacuum pressure, the vacuum pressure device determines how many cells are there. It shuts the vacuum off, and then

that little filter, 2-centimeter filter of cells is turned upside down

on a slide, and a positive pressure puts the cells in the slide. What

it does is it removes potentially obscuring materials, especially vaginal discharge. It disperses the cells on a slide in what is called a

monolayer, so that the cells are not overlapping each other. So

what it allows is for the slide to be looked at by the cyto-tech without having the potential of inability to see individual cells.

I should actually have, Ms. Gatscha, or a——

Ms. GATSCHA. Yes.

Mr. COX. There you are. I couldn’t see you there for a minute.

Basically, that would be something for you to comment on as well.

So that is a thin-prep process, and it has been evaluated in the

ALTS trial as well as HPV testing.

Mr. COBURN. Okay, there’s just one followup. Could you let the

panel know that the difference is in cost in your area for a thinprep versus a conventional pap?

Mr. COX. Right. Well, my wife had one recently and it was $60.

I don’t know; I think the lab charges for—this is private paid—the

lab charges $32 or $34 for conventional pap. For the health center,

I can say that the conventional Pap is $10. The thin-prep Pap is

$20. Basically, the thin-prep Pap has a set incremental fee that has

to be attached until the prices come down, and that is that it is

$9.75 for the materials that are disposable in the pap, because of

the filter, the liquid media, and some element of usage of the thinprep machine which cost in itself for the lab to get.

Mr. COBURN. The gentleman from Ohio.

Mr. BROWN. Thank you, Mr. Chairman.

I think you heard, I think all three of you were sitting there patiently during the last panel, and I had a discussion with Dr. Lee

about MQSA, what Congress did with that and with licensing and

inspection of mammography facilities, and how that, I think, has

been a true success across the country. Could you comment, I suppose especially Ms. Gatscha, but really all three of you, on any

thoughts you would have with—obviously, with mammography facilities there is not the problem, as Dr. Lee said, as with Pap

smears of 50 percent of errors due to healthcare provider errors, 50

percent lab errors. I mean, it is obviously a different phenomenon

with MQSA and with mammography facilities.

But could you run through what might make the most sense in

terms of better national licensing or annual inspections or licensing

and training of personnel or what we might want to do?

Ms. GATSCHA. Yes. What I have found to be the most remarkable

thing that has happened is CLIA-88. Many laboratories that were

called into question in all of these articles that we read in The Wall

Street Journal, et cetera, have been forced to institute quality assurance programs. And that, in my estimation, has been the

strongest avenue to pulling the test results into place—getting
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more accurate results, results that correlate with surgical pathology. I think that has been the strongest impetus.

Mr. BROWN. Dr. Lenhart, do you have any thoughts on it?

Mr. LENHART. Well, I think you have to take into consideration

more that we are just beginning to regulate those who read the

slides. Because some of the newer techniques involve less and less

technology from the individual pathologists. The auto-prep and

papnet involve computerized technologies. So that if you were only

to look at making sure that—it is not really analogous to mammography. That is why we are proposing that the public as well as

healthcare providers start thinking about the best way to use these

enhanced technologies. Because they might eliminate some of those

errors through the enhanced technologies without the regulation.

They also might allow for screening to occur less frequently. They

also might make it clear to those women who are dealing with borderline paps who is really at risk and who isn’t, which would eliminate a lot of anxiety. So we see it as more complicated than just

looking at how to make sure that those who read Pap smears do

it consistently and well.

Mr. COBURN. Would the gentlemen yield for just a second?

Have there not been a couple of studies that have already

showed those advanced technologies as improving our diagnostic

skills at a lower cost?

Mr. LENHART. Yes.

Mr. COX. You know, I think enhancing regulation will not be

very helpful. I think it is clear CLIA-88 has had a major impact

on lab quality in almost every area except Pap smear. There have

been several good studies on the 10 percent rescreening, and it has

shown that really the amount of disease picked up by 10 percent

rescreen is very, very little. I think that if we are going to really

look at how to make the system work better, we have to realize

that a false negative pap, only about 30 percent are screening or

interpretive errors. There is the other 70 percent that are sampling

or preparation errors or cells just not on the slide, for whatever

reason. And if we are going to make a major impact in this problem, we need to try to improve the Pap upfront, if that is possible.

Now, I think the thin-layer cytology does improve the Pap smear

upfront, but on a year-to-year, on an annual basis of using it annually, it probably is not cost-effective, unless we are willing to put

that extra money into it and just say it is a better test and that

we are willing to fund it. But if we really look at the ability of a

better Pap to potentially allow us to increase the screening interval, and realizing that many people have an increased screening interval anyway—many people only go in every two or 3 years. So

if we have a better Pap applied to that, then in the end, we don’t

have to do paps every year, that would save substantial money

down the road.

Part of the reason it would save substantial money is that you

have to remember that 5 to 10 percent of women that go in and

get paps every year on an annual basis will get either an equivocal

Pap or a Pap that is limited in quality; both of those require a physician response, bringing the patient back for some response. So,

those are in many instances false positives. If we don’t have to do

that on a yearly basis and bring all of those in, but only have that
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risk, say, every 3 years, our system will get much more cost-efficient than it is right now, and we can still, I think, pick up as

much or more cancer than we are picking up under the present

system.

Mr. COBURN. The gentlelady from California.

Mrs. CAPPS. Thank you. I want to acknowledge—first of all,

thank you for your testimony, and I would like to address it briefly.

I know the hour is getting late, but we have sitting through this

whole discussion this afternoon Dr. Wanda Jones, from the Women’s Health Office, Department of Health and Human Services. I

think that is a credit to what they are doing in their office and also

bears a lot on what we are talking about today.

It calls to mind for me the United States Public Health Service,

in combination with the Department of Defense, this wonderful mobile unit for a mammogram, the state-of-the-art that I was able to,

when I was a congressional spouse, had a tour of. There are innovations happening in cancer detection here, in our Nation’s Capital,

but also all throughout the country. That is what I find intriguing

about it.

So I want to commend the efforts of the Women’s Health office

for what you do, and also the three of you are touching on—and

I know that it must be frustrating for you because we are barely

getting into the topics that you care so deeply about. But that is

the nature of what we do here. And right now, at this late hour,

we are getting to part of the discussion that we could really sink

our teeth into and say, you know, what is the next thing to do?

Here I feel such an dichotomy. We have a treatable disease, and

I have had a personal experience now. My daughter was just diagnosed with cancer, not this kind, within the last month. So I am

entered into a world that I didn’t think I would have to learn about

this way.

But here we have a preventable disease, according to a screening

device, which is fairly routine, and I hear from you, Ms. Gatscha,

the reimbursement rate has something to do with how effective

this is going to be and we need to be addressing that here on the

Hill. Also, we have the challenge of getting this screening out to

more women and having them know more about—well, not just

women, our society in general. I don’t want to pin it all onto

women—to know what to do about our bodies and how to prevent

preventable diseases. So we don’t want to lose that track.

Yet, you are saying we should be going the next step. We

shouldn’t be content with the Pap smear that was around 50—I

know it has been improved, but maybe there is different concepts.

So, with the little tiny bit of time, can you tell me how we should

proceed here on the Hill with this topic now? And thank you.

Mr. COX. Where I have a hard time answering that is I am not

sure what laws or power you have in terms of making changes in

this. My personal feeling is that the agencies that have been set

up to explore cost-effectiveness and cervical cancer screening have

taken only a single end-point and used a model that was made in

1985 or made in 1990, but used 1985, International Agency for Research on Cancer data. The model uses a $3 cost for Pap smears.

It uses a false negative rate of Pap smears of 2 to 3 percent. It uses

as the only end-point years of life saved, which if you divide the
99

number of lives lost in the United States per year by 50 million

women screened, comes out to very small numbers, especially when

you talk about enhancements that might improve that.

So, what I would really like to see you all encourage is that, in

those situations in which there are official assessments of cost-effectiveness, that really we take into account cost-benefit analysis

and quality-of-life years. Because those are what really matter to

women. Women are not at huge risk over their lifetime of dying of

cervical cancer, but they are at huge risk of getting anxiety and

distress over being diagnosed with something that may have little

adverse effect on them either now or in the immediate future.

I think that we can utilize cost-benefit analysis in a way in

which we can find that this system can be organized in a much better way than it is, and that it can be still as effective, and probably

more so, with not nearly so much trauma, both physical and psychological, to women.

So that is where I would like to take it. I would also mention

maybe not starting the screening interval at 18, and I figured I’d

get some real hackles out of people for that. I am basically in a center where I see 18- to 22-year-olds, and I have never seen a cancer

in this age group, not an epithelial cancer. I’ve seen rabdomile sarcomas, et cetera, but not epithelial cancers. And, indeed, epithelial

cancers are extremely uncommon in women under the age of 24.

So I think that we could consider, if we have to save money in

the screening system to put elsewhere, to higher-risk groups, et

cetera—maybe we don’t—but if we do, I think we could consider

looking at what the rest of the world does and make that screening

start a little bit later, especially in terms of the trauma that occurs

with young people considering the very high positive rate of HPV

in that group, the very high positive transient nature of the HPV

effect in that age group.

Mrs. CAPPS. Thank you. More flexibility then, or——

Mr. LENHART. I would like to add two thoughts that we learned

through the AMWA campaign that might be utilized on a more

Federal basis. The first is the importance of involving multi-specialty groups in formulating policy. Our advisory committee not

only included pathologists, cytologists, and some experts in virology, but also practicing clinicians, both primary care physicians,

obstetrician, gynecologists. It was a very variable group. And if you

want to really tease out cost-effectiveness, and the complexity of

the issue, you want to develop policy based on a consensus group

that is more variable than is often involved.

The second thing that we learned was not to underestimate the

low cost in high efficiency of women’s capacity to be pro-active and

to communicate. The cost of our campaign is relatively low because,

essentially, we took our multi-specialty advisory committee, said,

what are the key things that women should know that they don’t

know about both what’s new and about what they should be doing

more of? Then we gave that information free of charge to a number

of women’s organizations, many of them minority organizations,

and said to them, ‘‘This is what is important. You figure it out.’’

We gave them suggestions. ‘‘But you figure out the best way to get

this information across to your groups.’’ That is pretty cheap.
100

Mr. COBURN. Dr. Lenhart, let me interrupt and give Mr. Towns

his time, if we may. We are running way over, and many of us

have to be in other places about 10 minutes ago. The gentleman

from New York.

Mr. TOWNS. I will definitely try to respect that, Mr. Chairman,

and be as brief as possible.

You know, I guess I want to ask each panelist this. In your opinion, what is the greatest constraint for women to get access to quality Pap smears? What is the greatest constraint?

Mr. COX. There is a whole slew of studies and literature on this

right now. And, unfortunately, they are not going to help answer

that question very much because most of them have indicated the

cost is not the primary issue. And, in fact, you can look at the Kaiser system, and you can look at the Canadian system, where cost

is not a factor—women get free access to Pap smears—and, yet,

this same percentage of women that get cervical cancer in that system are those women that don’t get screened. So, it is not, it

doesn’t appear to be a cost issue.

There really are societal, cultural issues, especially cultural, that

we have a harder time penetrating, and especially in our wonderfully diverse society we have so many cultures come in, in which

really something that is in that part of the human anatomy is really not something that is shown even for exam. And, it is those

kinds of issues that we have a hard time getting beyond. If we can

find ways to overcome the cultural and societal issues, then I think

that we may be able to get many, many of these women in. But

that is the hardest thing to crack, I believe.

Mr. TOWNS. Let me ask you, Doctor, if they come in—I am not

sure that I am hearing that the medical staff encourages them,

even when they come in. Then when they come in for something

else, do they actually encourage them to take a Pap smear? Is that

going on? I get the feeling that there is something missing here.

Mr. COX. I agree. I think that what you are alluding to is that

there are often visits to the medical practitioner by patients, by

women, who have never had a Pap or have not had one in many,

many years, and they are there for some other reason and the Pap

smear is not done. And I think that is one of the things that we

have to do. We have to educate physicians to always be wary of the

fact that when a woman comes in, a Pap needs to be done.

Kaiser published a good study in the Green Journal this year in

which they showed that 60 percent of the cancers in their population were in women that had not had a Pap smear or not had

one in the last 5 years, and the majority of those women had been

in the Kaiser system for some other reason and had just not had

a Pap when they were there. This is a real tragedy and something

that has got to be corrected.

Mr. LENHART. We would agree with that. We think that a lot of

the new information, as well as a lot of vital women’s health information in general, is often missed in the doctor’s office. So we have

sponsored a number of physician education programs that are targeted at getting the information out, as well as converting the doctors into advocates and better communicators, but also patients

into advocates and better communicators with their physicians. We

think that dialog is a very important one to monitor.
101

Mr. TOWNS. Do you want to add to this?

Ms. GATSCHA. Yes, well, just one thing really, because those are

the cruxes of this matter. But I think, also, this information has

to be disseminated at other levels because there are lots of people

who don’t go to a doctor. They are just well. They don’t go and no

one says, ‘‘Hey, have you had a Pap smear?’’ I think that at the

community level, churches, schools, this information has to be part

of health programs in elementary and high schools. Hopefully, by

college, when many young women do become sexually active, then

they will have these tools to use to help them prevent this disease.

Mr. TOWNS. Thank you. Just one other question which is sort of

really bothering me: Is it realistic to expect that women, and particularly low-income women, will have access to new cervical cancer

treatment? Is it realistic to think that they will.?

Mr. COX. Well, I think that resources are available in most

States. I can only answer for my State—that that there are resources for almost all women to get Pap smear screening. There is

Medical/Medicaid. There is State Office of Family Planning, which

provides Pap smears to women coming in for family planning. I

think that it is uncommon in the State of California for there to

be women totally outside the system, unaffordable. Even for women

that are caught between the really low-income level and the job

level where they have insurance coverage, there are some women

that are not rich and not poor and don’t have insurance. Those are

the ones that often have the hardest time, but paps are available

through Planned Parenthood, for instance, and other agencies on a

sliding scale that can be very helpful for those women.

I think one of the things we forget is that Planned Parenthood

provides about 2.5 million paps in the United States per year. It

provides more paps than any other organization in the United

States, and so that is a very important function for it, that women

that might otherwise slip through the cracks would have access to.

Mr. COBURN. Would the gentleman yield?

Dr. Lee did testify—she was asked that specific question by Ms.

Eshoo, and her response was, they are getting the care, you know,

which surprised me. I will just admit to you I was surprised at her

answer, and I am going to ask her for that data, which leads me

to the next question.

I would like unanimous consent to add to the record and leave

the record open until the questions are formulated for our panel.

Other then that, I want to thank each of you for being here and

for your contribution and your time.

Mr. COX. Thank you very much.

Mr. COBURN. The meeting is adjourned. I guess you do this:

[using gavel].

[Whereupon, at 5:45 p.m., the subcommittee was adjourned.]

[Additional material submitted for the record follows:]

PREPARED STATEMENT OF CAROL ANN ARMENTI, DIRECTOR, CENTER FOR CERVICAL

HEALTH

It is my privilege to contribute to these proceedings on cervical issues as a cervical

cancer survivor, a patient advocate and a healthcare professional. In a recent media

interview I was asked with how many women did the Center for Cervical Health

have direct contact over the past year. I was surprised to find that our website,

which we are proud to say has been reviewed, approved by and linked to such pres-
102

tigious organizations as Yale University, the Women’s Cancer Network, and the Society of Gynecological Oncology, receives several thousand accesses a week, and that

I personally counsel and refer for treatment as many as a dozen women in a week.

It has been my distinct pleasure and honor this past year to be the first patient

advocate appointed to the American Medical Association National Patient Safety

Council, to serve as the New Jersey State Cervical Chair of the Center for Disease

Control Breast and Cervical Program, and to be cervical cancer survivor representative to the National Cancer Institute Survivorship Research Conference. I served on

the National Institute of Health cancer survivorship grant funding panel which—

for the first time—permitted advocates a full vote on funding proposals. It was a

similar honor to testify before the Food and Drug Administration, this past year,

on new technologies in the detection of cervical disease.

I am blessed with the support of the print and broadcasting media, advocacy organizations, medical groups and private industry. But I am most blessed with this opportunity to represent to you the courage of those suffering from cervical disease

in this country, it is with frustration and anger on their behalf that I advise you

of their unmet needs, and it is with hope that I ask for the increased support they

deserve.

I call to your attention that fourteen per cent of all cancer survivors are those

surviving cervical cancer. Other than breast cancer, it arguably represents the largest group surviving any form of cancer in this country yet relatively little is done

to support these women who have had what is unique to their being, their reproductive organs, mutilated and destroyed. This past week at a National Cancer Institute

Survivorship Research Conference not one research project which focused on cervical

cancer was presented in two days of lecture.

Of the nearly eighty grant proposals on cancer survivorship submitted to the National Institute of Health not one—other than a DES follow-up study—focused on

cervical cancer. Indeed, I was recently contacted by a cancer center in Colorado

which was attempting a study on cervical cancer survivors. The researchers were

disconcerted because they could not find more than two dozen cancer survivors eligible and willing to participate in a study. I immediately contacted two prominent

cancer advocates whom I know to be surviving cervical cancer and I was told that

they did not wish to become ‘‘public.’’

Our society has branded these women pariahs. They are ashamed to discuss their

disease, and even worse, they are so embarrassed to discuss their symptoms that

they frequently do not seek detection of early precursor conditions or obtain effective

treatment of disease. It is incumbent upon us as a nation to provide women with

the education they need in their earliest, as well as their latest, years to protect

their lives and their reproductive system. It is further incumbent upon us as a nation to provide adequate funding and assurances that women who seek detection

and treatment will receive it.

Strides are currently being made in the areas of detection, new technologies which

may prove successful in determining the genesis of disease. New treatments and

vaccines are showing great promise for the reduction in morbidity and mortality of

cervical disease. Yet I see little improvement in the education of young women

which may help them make better choices. We must see programs which will inform

all women on the damage to their reproductive systems caused by smoking, and inform young women especially of the increased risk to which they expose themselves

by relations in their teenage years when their immune systems may be especially

unable to fight disease.

Similarly, I see little in this country done to educate physicians to the symptoms

of cervical disease and even less done to inform them on new methods of detection

and treatment.

Nearly two years ago because of the great silent suffering of these women who

were willing to share their experiences with me both as a sister survivor and psychologist, I began my efforts to increase public awareness. Part of those efforts resulted in the declaration of January as Cervical Health Month by this administration. Our reward was dozens of programs across the country encouraging women to

protect themselves by having Pap tests, the single most successful cancer screening

device ever devised, and to have pelvic examinations. Part of our efforts is the Resolution, consistent with its predecessor sister resolution for breast cancer survivors,

currently before the Senate declaring Cervical Health Month and conveying the

sense of the Senate that these women and their families deserve support.

I further ask this Committee to support increased funding programs for the detection of cervical disease. It is oftentimes said that fully half of the women who develop cervical cancer did not receive a Pap test. This statement is made as an indictment of those women who develop the disease as if they were somehow responsible

for their own illness. In the State of New Jersey we are both proud and saddened
103

to say that we gave a party and everyone came. That is, not only did we achieve

our goals in the numbers of women who responded to our CDC underserved program, more women came than we had funds to test. We must ensure that all women

who wish to be tested, are tested.

I ask that this Committee encourage studies which will ease the burden of those

surviving cervical cancer. We can learn from these women how best to treat future

disease with less destruction and less mortality. I call to your attention that while

the death rate of other cancers has declined, the mortality rate of cervical cancer

is expected to increase this year.

Finally, I ask that you encourage the education of both women and physicians on

causes, symptoms and treatments of this disease, and that we do so without the

moral judgment which has made women too ashamed in the past to seek detection

and treatment.

I once again thank you for this opportunity to address this Committee.

DEPARTMENT OF HEALTH & HUMAN SERVICES

NATIONAL CANCER INSTITUTE

April 8, 1999

The Honorable MICHAEL BILIRAKIS

Chairman, Subcommittee on Health and Environment

Committee on Commerce

House of Representatives

Washington, D.C. 20515

DEAR MR. CHAIRMAN: I am responding to your letter of March 19, 1999, in which

you pose five questions as a follow-up to my testimony before the Subcommittee on

Health and Environment on March 16, 1999.

As requested, the questions have been restated below. The answer follows each

numbered question.

Question 1. What are some of the side effects of various forms of cervical cancer

treatment?

Response. Three kinds of treatments are used for cervical cancer: surgery, radiation therapy and chemotherapy and side effects vary depending on the type of

treatment chosen. There are also several different types of surgery that are used

to treat cervical cancer. The stage of cervical cancer at the time of diagnosis determines the type of treatment and will determine possible side effects.

Methods for removing or destroying small cancers on the surface of the cervix include: cryosurgery which kills the cancer by freezing; cauterization (burning) or

laser surgery which destroys the abnormal area without harming nearby healthy

tissue; a loop electrosurgical excision procedure (LEEP) may be preformed in which

an electrical current is passed through a thin wire loop that acts as a knife to remove the abnormal tissue; and conization in which a cone-shaped piece of tissue is

removed where the abnormality is found. These treatments may cause cramping or

other pain, bleeding, or a watery discharge.

Hysterectomy is another surgical procedure used in the treatment of advanced

cervical cancer. Women who have a hysterectomy may experience pain in the lower

abdomen for a few days following surgery. They will no longer have their menstrual

periods and can no longer have children. Sexual dysfunction is another possible side

effect. Women who undergo hysterectomy also face the risks of major surgery, including bleeding, infection, and damage to other organs.

Side effects of radiation treatment can include infertility, sexual dysfunction, fatigue, hair loss, skin conditions, diarrhea, and frequent and uncomfortable urination.

Side effects of chemotherapy depend on the drugs and doses the patient receives.

Side effects can include increased susceptibility to infections, bruising, low energy,

hair loss, poor appetite, vomiting, and mouth sores. Side effects gradually go away

during the recovery periods between treatments. Women treated with cisplatin can

also develop chronic neuropathy and renal damage.

Question 2. How can screening methods for cervical cancer be improved?

Response. The Pap test is currently the accepted method used to screen for cervical cancer and has been very successful in reducing the death rate from cervical

cancer. However, as with any medical test, the Pap smear has limitations, particularly with respect to false-negative screening results. Recently, interest has focused

on development of technologies to enhance the accuracy of cervical cancer screening.

Some of these techniques are directed at improving the sampling and specimen

quality, others are focused on improving the laboratory microscopic screening process, and some techniques are visual or molecular rather than microscopic.
104

Methods to improve sampling and specimen quality include the use of liquidbased collection techniques. Liquid-based collections offer improved fixation and

presentation of the material in a more uniform manner than traditional smears

which could make detection of abnormal cells easier. This technique also has the

ability to test for HPV infection if there is a low-grade or equivocal cytology result

which eliminates additional patient visits for testing.

Computer image analysis has been approved to screen cervical cytology specimens

in an effort to reduce false-negative results. While this technology increases the

screening sensitivity for atypical squamous cells of undetermined significance and

low grade squamous intraepithelial lesion diagnosis it comes at a significant cost.

Used in a secondary screening mode, these technologies are cost-effective only if incorporated into a less frequent screening strategy.

Question 3. What type of education campaign has the National Cancer Institute

(NCI) sponsored to increase the awareness of cervical cancer? Please be specific in

describing how NCI has coordinated its activities with other Federal agencies and

programs.

Response. Federal agencies are designated to serve the United States in specific

ways. The National Institutes of Health (NIH), of which NCI is a part, is a research

agency. In its mission to protect and improve human health, the NIH (and NCI)

conducts and supports basic, applied, and clinical and health services research to

understand the processes underlying human health and to acquire new knowledge

to help prevent, diagnose, and treat human disease and disabilities. This may include developing an information campaign such as the Pap Tests: A healthy habit

for life campaign and evaluating its effectiveness at achieving its goal. NCI also has

a mandate to disseminate research findings so that when the development and evaluation are completed, other Federal and state agencies, and private sector organizations, may take this information and apply it accordingly. NCI, therefore, plays an

integral role in these activities.

The NCI disseminates research findings widely through scientific publication,

press conferences, press statements, clinical alerts, patient education materials,

meetings of professional societies, television and radio, the World Wide Web, our

toll-free Cancer Information Service, our PDQ databases, and the Information Associates Program. Our staff has many contacts within agencies for a variety of programs and issues. Through these personal contacts, and those mechanisms mentioned above, Federal agencies and offices have direct access to information pertinent to their programs. In addition, we maintain and foster close working relationships with other Institutes that have formal collaborative relationships with the Office os Population Affairs-our projects and programs are thus included in that broad

knowledge base. NCI has several partnerships with other federal agencies and nonfederal groups to enhance our information dissemination activities The following are

examples of two specific information campaigns on cervical cancer:

Pap Tests: A healthy habit for life: In May 1998 the Office of Cancer Communications began a campaign to alert the public of the results of a survey that

showed that older women were unaware of their continued risk for cervical cancer. National activities have included the distribution of a media packet that focused on cervical cancer and older women. Additionally, NCI collaborated with

the Health Care Financing Administration (HCFA) to reprint an NCI cervical

cancer publication with Medicare information for older women. Other activities

have included conducting research with physicians to identify their attitudes

and perceptions of Pap test screening among women 65 and older. Based on this

research, a print public service announcement and newsletter article are being

developed that encourage physicians to talk to their older patients about Pap

test screening. These materials will be promoted through physician publications

and newsletters.

The Pap Test and Cervical Cancer Video: An intertribal video on the early detection

of cervical cancer for American Indian women was produced by the NCI in conjunction with the Nebraska Department of Health. The video comes with educational material to help inform American Indian women of the importance of

regular Pap tests.

Question 4. What is being done to improve the quality of life for women who are

diagnosed and treated for cervical cancer?

Response. Improving the quality of life for cancer patients is a very important

part of research at NCI. Currently, NCI is working to evaluate interventions which

can reduce sexual dysfunction caused by radiation therapy. In addition, the NCI has

ongoing research on ways to reduce damage to normal tissue from radiation therapy. The NCI also has plans to study fertility-sparing surgery for women with early

stage cervical cancer.
105

Question 5. In your testimony, you discussed clinical trials that NCI is conducting

on cervical cancer. What is the percentage of cervical cancer patients who participate in these trials?

Response. Approximately 2-3% of women diagnosed with cervical cancer are enrolled on cancer treatment trials sponsored by the NCI. This figure is consistent

with other adult cancer sites.

Please do not hesitate to contact me if you have further questions.

Sincerely,

EDWARD L. TRIMBLE, M.D.

Head Surgery Section, Division of Cancer Treatment and Diagnosis

DEPARTMENT OF HEALTH & HUMAN SERVICES

NATIONAL CANCER INSTITUTE

April 8, 1999

The Honorable MICHAEL BILIRAKIS

Chairman, Subcommittee on Health and Environment

Committee on Commerce

House of Representatives

Washington, D.C. 20515

DEAR MR. CHAIRMAN: I am responding to your letter of March 19, 1999, in which

you pose twelve questions as a follow-up to my testimony before the Subcommittee

on Health and Environment on March 16, 1999.

As requested, the questions have been restated below. The answer follows each

numbered question.

Question 1. The National Cancer Institute (NCI) is in the process of conducting

a randomized trial to establish the best way to manage abnormalities that are discovered during Pap smear tests. This study is often referred to as ASCUS/LSIL

Triage Study or ALTS. Please explain the purpose and significance of this trial?

Response. NCI is conducting a large randomized trial to find the best way to manage the mild abnormalities that often show up on Pap tests and may, in rare instances, progress to cancer if left untreated. The ALTS trial is comparing three approaches: 1) immediate colposcopy (a procedure in which a physician examines the

cervix through a magnifying instrument and biopsies any abnormal area; 2) repeating the Pap test every six months (because most abnormalities return to normal

without treatment); and 3) testing for cancer-associated types of HPV as a means

to differentiate between abnormalities that need immediate colposcopy and those

that can be best followed with repeat Pap tests. Researchers will compare the three

different groups to assess the effectiveness of each management option in detecting

the serious abnormalities that can progress to cancer, the acceptability of each option to patients, and the cost effectiveness of each option.

Question 2. When do you estimate the NCI will develop a vaccine for human

papillomavirus (HPV)? Can you describe all of the different HPV vaccines that are

being tested?

Response. There are both preventative and therapeutic HPV vaccines which have

been developed by the NCI that are currently being tested in clinical trials. They

seek to prevent infection or to induce regression of established infection via immune

recognition of specific HPV-encoded proteins or peptides. Such vaccines can be delivered either directly as a protein or by viral vectors derived from organisms of a different but related species.

Question 3. What effect, if any, does HPV have on men?

Response. Scientists have found an association between several types of HPV and

the development of anal cancer and cancer of the penis (a rare cancer). HPV also

frequently causes benign warts.

Question 4. In addition to cervical cancer, what other effects can HPV have on

the body?

Response. Genital warts (condylomata acuminata or venereal warts) are caused

by only a few of the many types of HPV. Other common types of HPV infections,

such as those that cause warts on the hands and soles of the feet, only rarely cause

genital warts. In women, the warts occur on the outside and inside of the vagina,

on the cervix, or around the anus. In men, genital warts are less common. If

present, they are seen on the tip of the penis or the urethra; however, they also

may be found on the shaft of the penis, on the scrotum, or around the anus. Rarely,

genital warts also can develop in the mouth or throat of a person who has had oral

sexual contact with an infected person.

Question 5. Please provide the number of HPV cases in the U.S. Is this number

increasing or decreasing? To what can this trend be attributed?
106

Response. It is important to remember that estimating the prevalence of HPV is

difficult. Prevalence depends on many factors which include: the population

screened, the sexual habits of those screened, what is classified as HPV infection

at the time of screening, etc. Estimates for the number of HPV cases varies. In November of 1996 the CDC estimated that 24 million Americans were infected with

HPV. The incidence of HPV infection has increased with changing sexual mores

starting in the 1960’s. It is difficult to know whether variations in incidence and

prevalence reported during the 1990’s represent an actual change in the number of

cases of HPV.

Question 6. What, if any symptoms are associated with HPV? If it is asymptomatic, how would one know one is infected?

Response. HPV may cause warts with many different characteristics. They may

appear small or large, flat or raised, single or multiple; sometimes the warts may

not even be visible to the naked eye. The most common places to notice genital

warts are outside the vagina, on the penis, and around the anus. In women, HPV

can lead to the development of warts inside the vagina and on the cervix as well.

For many people who have HPV infection, there are no obvious signs of infection.

However, if warts are present, a doctor can diagnose HPV infection by their characteristic appearance and the history of how they developed. In women, to look for

warts on the cervix or in the vagina, a doctor may use a colposcope, which is like

a telescope. In addition, Pap smear results may be suggestive of HPV infection.

There is currently no blood test that has proven reliable in the diagnosis of HPV

infection and it is not possible to routinely culture HPV. However, there are sensitive DNA based assays which can be used to diagnose symptomatic and asymptomatic HPV infection.

Question 7. How widespread or common is HPV? Of the women who have HPV,

what is the percentage of those women who will develop cervical cancer?

Response. More than 80 types of HPV have been identified. However, approximately 25 types infect the uterine cervix; of these, only some are associated with

invasive cervical cancer. They are therefore classified into low-risk types, HPV 6 and

11, and high-risk types, most commonly 16, 18, 31, and 45, which account for more

than 80 percent of all invasive cervical cancers. Less than 15 percent of women infected with HPV will develop either low-grade squamous intraepithelial lesions

(LSIL) or high-grade squamous intraepithelial lesions (HSIL). At least one-third of

all grades of SIL will fade, whereas less than half persist and approximately onequarter progress. Of lesions that progress, approximately 10 percent progress to carcinoma in situ and 1 percent to invasive cancer.

Since the virus is transmitted primarily through sexual intercourse, there seems

to be a peak prevalence of infection in sexually active women who are younger than

25 years of age. The prevalence of infection decreases with increasing age, suggesting that most infections in women and men resolve over time through host immune responses.

Question 8. The NCI has identified risk factors, such as the human

papillomavirus, in the development of cervical cancer. What work has NCI done to

coordinate a Federal response to the prevention of cervical cancer? Specifically, what

has NCI done to coordinate with the Department of Health and Human Services

(HHS) Office of Population Affairs and the HHS Health Resources and Services Administration (HRSA) to alert women concerning the risk factors associated with cervical cancer?

Response. Federal agencies are designated to serve the United States in specific

ways. The National Institutes of Health (NIH), of which NCI is a part, is a research

agency. In its mission to protect and improve human health, the NIH (and NCI)

conducts and supports basic, applied, and clinical and health services research to

understand the processes underlying human health and to acquire new knowledge

to help prevent, diagnose, and treat human disease and disabilities. This may include developing an information campaign such as the Pap Tests: A healthy habit

for life campaign and evaluating its effectiveness at achieving its goal. NCI also has

a mandate to disseminate research findings so that when the development and evaluation are completed, other Federal and state agencies, and private sector organizations, may take this information and apply it accordingly. NCI, therefore, plays an

integral role in these activities.

The NCI disseminates research findings widely through scientific publication,

press conferences, press statements, clinical alerts, patient education materials,

meetings of professional societies, television and radio, the World Wide Web, our

toll-free Cancer Information Service, our PDQ databases, and the Information Associates Program. Our staff has many contacts within agencies for a variety of programs and issues. Through these personal contacts, and those mechanisms mentioned above, Federal agencies and offices have direct access to information perti-
107

nent to their programs. In addition, we maintain and foster close working relationships with other Institutes that have formal collaborative relationships with the Office os Population Affairs-our projects and programs are thus included in that broad

knowledge base. NCI has several partnerships with other federal agencies and nonfederal groups to enhance our information dissemination activities. Following are

examples of two specific information campaigns on cervical cancer:

Pap Tests: A healthy habit for life: In May 1998 the Office of Cancer Communications began a campaign to alert the public of the results of a survey that

showed that older women were unaware of their continued risk for cervical cancer. National activities have included focusing on minority media outreach and

the distribution of a media packet that focused on cervical cancer and older

women. Additionally, NCI collaborated with the Healthcare Financing Administration (HCFA) to reprint an NCI cervical cancer publication with Medicare information for older women to be distributed through HCFA and NCI networks.

Other activities have included conducting research with physicians to identify

their attitudes and perceptions of Pap test screening among women 65 and

older. Based on this research, a print public service announcement and newsletter article are being developed that encourage physicians to talk to their

older patients about Pap test screening. These materials will be promoted

through physician publications and newsletters.

The Pap Test and Cervical Cancer Video: An intertribal video on the early detection

of cervical cancer for American Indian Women was produced by the NCI in conjunction with the Nebraska Department of Health. The video comes with educational material to help inform American Indian women of the importance of

regular Pap tests.

Question 9. Please name the NCI liaisons with CDC, HRSA, and the Office of Population Affairs. Has NCI coordinated activity with the Title V Abstinence Education

Grant Program or the Title XX programs within those agencies?

Response. As previously stated, NCI staff has many contacts within agencies for

a variety of programs and issues. Liaisons with CDC, HRSA and the Office of Population Affairs vary on the program and issue involved.

NCI has not formally collaborated specifically on Title V Abstinence Education

Grant program or the Title XX programs. As a research agency, NCI’s role is to conduct and support research, then disseminate widely, new knowledge gained. This is

done through information campaigns like the Pap Tests: A healthy habit for life

campaign.

Question 10. What is the amount of research dollars spent by NCI on HPV as

compared to the virus that causes AIDS? How many women die annually in the

United States from cervical cancer? How many women die annually in the United

States from AIDS?

Response. There are over 80 types of HPV, about 15 of which are associated with cancer of the cervix. NCI estimates that it will spend about $38 million on cervical

cancer-related HPV research, and about $235 million on AIDS related cancers, in

FY 1999. There are about 5,000 deaths in the U.S. from cervical cancer each year,

and more than 200,000 deaths world wide. Over 90 percent of these cancers are

HPV-related. There were about 4,600 female deaths in the U.S., and 900,000 worldwide, from HIV-related illness in FY 1997.

Question 11. On January 12, 1999, Chairman Bliley sent a letter to the NCI on

women’s health issues, including cervical cancer. In response to that letter, NCI estimated the number of Americans with HPV to be 24 million. In testimony before

this committee by Dr. Ronald Valdiserri, of the Centers for Disease Control and Prevention (CDC), on March 16, 1999, he indicated that number is 45 million. Can you

explain the discrepancy in numbers?

Response. The NCI estimated number of Americans with HPV came from the

CDC website. The entry title is ‘‘The Challenge of STD Prevention in the U.S.’’ and

it was written in November 1996. CDC was not contacted by NCI for verification

of this number and the CDC testified using an estimated number that may be more

current than the one posted. Once again, it is important to remember that estimating the prevalence of HPV is difficult. Prevalence depends on many factors

which include: the population screened, the sexual habits of those screened, what

is classified as HPV infection at the time of screening, etc.

Question 12. In the above referenced letter from NCI to Chairman Bliley, NCI

stated that, ‘‘Condoms are ineffective against HPV because the virus is prevalent not

only in mucosal tissue (genitalia) but also on dry skin of the surrounding abdomen

and groin and it can migrate from those areas into the vagina and cervix.’’ That letter went on to say that ‘‘additional research efforts by NCI on the effectiveness of

condoms in preventing HPV transmission are not warranted.’’ To the contrary, Dr.

Ronald Valdiserri of CDC testified on March 16, 1999 that ‘‘Several studies have
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shown condoms to provide some protection against cervical cancer . . .’’ Can you explain the difference in conclusions made by CDC and NCI?

Response. The NCI conclusion that condoms are ineffective against HPV infection

is based on the results of several long term studies which have failed to show that

barrier contraceptives prevent cervical HPV infection, dysplasia, or cancer (Attachment 1, 2, 3). Dr. Valdiserri’s testimony might be based on studies that show that

while condoms are ineffective in preventing transmission of HPV, they are quite effective at preventing transmission of HIV and other sexually transmitted diseases.

CDC would be able to provide insight into the basis of Dr. Valdiserri’s statement.

Please do not hesitate to contact me if you have further questions.

Sincerely,

DR. DOUGLAS LOWY

Deputy Director, Division of Basic Sciences, NCI

Enclosures
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CDC RESPONSES TO QUESTIONS ON HPV AND CERVICAL CANCER FROM THE

SUBCOMMITTEE ON HEALTH AND ENVIRONMENT

Question: 1. How does CDC decide for which sexually transmitted diseases it will

compile surveillance data? Please provide a list of all sexually transmitted diseases

for which CDC currently recommends that states compile data. Please provide the

number of female deaths per year associated with the sexually transmitted diseases

for which the CDC has surveillance data.

Answer: Notifiable diseases are determined by individual state laws, not by CDC.

All reports of notifiable diseases to CDC are voluntary on the part of the states.

Generally, CDC compiles surveillance data for sexually transmitted diseases that

are notifiable in all 50 states (gonorrhea, syphilis, chancroid; chlamydia is reported

in 49 states). CDC also monitors non-notifiable diseases such as genital herpes by

conducting special prevalence studies in the U.S. population (e.g., the National

Health and Nutrition Examination Survey) and in smaller subpopulations. These

kinds of special studies define the disease burden in the U.S. and often establish

the need for diseases to become notifiable at the state level.

According to a CDC study, there were 2,665 female deaths attributable to HIV,

99 to syphilis, and 3 to gonorrhea in 1992, the latest year for which comparable data

are available (Ebrahim et al. Mortality related to STD in US women, 1973 through

1992. American Journal of Public Health 1997;87:938-944).

Question: 2A. Can the human papillomavirus (‘‘HPV’’) be transmitted in non-sexual manner? 2B. How can someone prevent its transmission?

Answer: A. Of the approximately 80 different types of HPV infection, about 50 are

considered to be non-genital (i.e., almost never occur on genital skin) and are almost

always transmitted in a non-sexual manner. Of the approximately 30 genital types,

sexual intercourse appears to be the predominant route of transmission. However,

it has also been suggested that in rare cases, infection of genital skin with HPV can

result from vertical transmission (mother-to-child during vaginal delivery);

‘‘autoinoculation’’ of non-genital types of HPV to the genital skin from another body

part (such as the hand); inoculation through casual contact with genital skin, such

as bathing; or transmission by inanimate objects (such as towels). (Cason, 1995).

B. The most reliable means of preventing sexual transmission of genital HPV infection is likely to be abstinence, although, as noted above, non-sexual routes of

transmission are possible. Other means of protection are more uncertain. The protection provided by condoms has been difficult to evaluate because current laboratory tests for HPV infection cannot determine whether an infection is new or acquired months or even years before. Latex condoms should provide protection if they

cover the infected genital skin and if used consistently and correctly. The greater

surface area of the female condom may provide even greater protection, although

there are no data evaluating its effectiveness in this regard. Finally, microbicides

under development may provide some protective benefit (Howett, 1999). The most

promising approach for prevention of transmission will be the development of preventive vaccines. Carefully designed studies of all of these transmission prevention

approaches will be important in designing more effective prevention strategies.

Question: 3A. Can the body eliminate HPV from its system? 3B. What can be done

for those people who have compromised immune systems?

Answer: A. Whether the body can eliminate HPV from its system, that is, totally

eradicate it (which is what we think happens with respiratory viruses such as those

which cause influenza or the common cold) has been difficult to determine. There

is good evidence that in most people genital HPV infections become ‘‘undetectable’’

by even highly sensitive lab tests for detection of HPV DNA (such as PCR) over the

course of a few months to a few years (Ho, 1998), and it appears that such people

do not have an increased risk for development of dysplasia or cancer. On the other

hand, people with persistently detectable HPV infection appear to be at higher risk

for dysplasia, and probably also cancer.

Evidence which suggests that undetectable HPV infection might not be totally

eradicated from the body comes from patients with compromised immune systems,

such as those taking immunosuppressive medication after an organ transplant or

those with HIV infection, in whom the rate of detectable HPV infection is much

higher than it is in patients whose immune systems are normal (Sun, 1997; Halpert,

1986). While some of this difference could be attributed to a greater risk of acquiring a new HPV infection among those with greater sexual risks (such as those with

sexually acquired HIV), the fact that the rate of detectable HPV increases directly

with declining immune function, even among patients who become less sexually active due to their illness, suggests that at least some or most of this excess level of

infection is due to reactivation of previously undetectable infection which was quies-
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cent but not completely eradicated. The similar experience in older, and probably

less sexually active transplant recipients, is also consistent with such a process.

B. For those with compromised immune systems, there are two current approaches to help them with potential HPV-related problems. The first is to be sure

that women undergo Pap smear screening at recommended intervals (which for

those with HIV infection is every 6 months for a year and then annually thereafter),

as well as follow-up evaluation of any abnormalities, in order to prevent what may

be an increased risk of cervical cancer. The second approach is to attempt to maintain and improve immune function if possible, such as with the use of highly active

antiretroviral therapy in those with HIV infection, which has the potential to reduce

the risk of HPV-associated dysplasia and cancer. Better studies are needed to help

develop management approaches in people with compromised immune systems.

Question: 4. On January 12, 1999, Chairman Bliley sent a letter to the National

Cancer Institute (NCI) on women’s health issues, including cervical cancer. In response to that letter, NCI estimated the number of Americans with HPV to be 24

million. In testimony before this committee on March 16, 1999, you indicated that

number is 45 million. Can you explain the discrepancy in numbers?

Answer: Because HPV infection is not diagnosed in most people who are infected

and because there are no systems in place for reporting of HPV infection, assessment of prevalence can only be based on very general estimates. This issue is further complicated, as noted in the answer to Question 3, by the problem that it has

not yet been determined whether infection no longer measurable by sensitive HPV

DNA detection tests such as PCR have truly resolved or are simply quiescent but

still present, which is the assumption made for other viral sexually transmitted diseases such as genital herpes.

With these complexities in mind, there have been several attempts to quantify the

prevalence of what are considered to be active genital HPV infections. Prior to 1999,

the most widely quoted estimate of active genital HPV infection was 24 million

(IOM Report). As of 1999, new revised estimates for the prevalence of the various

sexually transmitted diseases stated that ‘‘a conservative estimate of the prevalence

of productive HPV (persons with active shedding of HPV DNA) is approximately 20

million’’ (Cates, 1999).

Estimates of viral sexually transmitted disease prevalence based on serologic

studies (assessments based on the presence of antibody in the blood) are much higher. For genital herpes, the estimated prevalence is 45 million, and the number of

cases of genital HPV infection appears to be at least as great as the number of cases

of genital herpes. However, estimates of the number of people who have been infected (and might still be at least quiescently infected) with genital HPV based on

serologic studies are as high as 100 million (Koutsky, 1997).

Clearly, a very large number of Americans have genital HPV infection, and better

studies are needed to further refine these estimates.

Question: 5. NCI stated that ‘‘additional research efforts by NCI on the effectiveness of condoms in preventing HPV transmission are not warranted.’’ CDC’s testimony stated ‘‘Several studies have shown condoms to provide some protection

against cervical cancer.’’ Please explain the difference in conclusions and also cite

the studies to which you refer.

Answer: NCI statement refers to genital HPV infection, not cervical cancer. Two

case-control studies documented a strong protective effect of condom use and cervical cancer. In one study in Utah, condom use was associated with a lower risk

of cervical cancer in women who had more than one sex partner; these women had

a 47% lower risk of cervical cancer compared to women who did not use condoms

(Slattery ML, Overall JC, Abbott et al: Sexual activity, contraception, genital infections, and cervical cancer: support for a sexually transmitted disease hypothesis.

American Journal of Epidemiology 1989;130:248-258). In another study conducted in

Los Angeles, women who used condoms for 2-9 years had a 50% reduction in risk

of cervical cancer, and those who used condoms for 10 or more years had a 60% reduction in risk, compared to women who had 0-2 years of condom use (Peters RK,

Thomas D, Hagan DG, et al. Risk factors for invasive cervical cancer among Latinas

and Non-Latinas in Los Angeles County. Journal of the National Cancer Institute

1986;77:1063-1077).

Other studies have not shown a protective effect (Hildeshim A, Brinton LA,

Mallin K et al. Barrier and spermicidal contraceptive methods and risk of invasive

cervical cancer. Epidemiology 1990; 1:226-272 and accompanying editorial Daling

JR, Weiss NS: Are barrier methods protective against cervical cancer? Epidemiology

1990; 1:261-272.)

Question: 6. The CDC has identified risk factors, such as the human

papillomavirus, in the development of cervical cancer. What work has CDC done to

coordinate a Federal response to the prevention of cervical cancer? Specifically, what
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has CDC done to coordinate with the Department of Health and Human Services

(HHS) Office of Population Affairs and the HHS Health Resources and Services Administration (HRSA) to alert women concerning the risk factors associated with cervical cancer? Who are the liaisons with CDC, HRSA, and the Office of Population

Affairs? Has CDC coordinated activity with the Title V and Title XX programs within those agencies?

Answer: CDC has developed effective partnerships with HRSA and OPA on a local

level. HRSA directs national health programs which improve the health of the nation by assuring quality health care to underserved, vulnerable and special-need

populations. Under HRSA’s direction, a nationwide network of 643 community and

migrant health centers, and 144 primary care programs for the homeless and residents of public housing serve 8.1 million Americans each year. CDC’s National

Breast and Cervical Cancer Early Detection Program (NBCCEDP) contracts with

many local HRSA health centers to provide services. Women eligible for CDC’s program are referred to HRSA services for screening, diagnostic and treatment services

as needed. To assist this effort, CDC and HRSA partnered on a successful conference, ‘‘Cancer Institute on Prevention and Treatment Strategies for Underserved

Minority Populations,’’ to focus effective outreach, prevention, screening, diagnosis,

and cancer treatment services for underserved minority populations.

The OPA, within the Office of Public Health and Science of the DHHS, provides

resources and policy advice on population, family planning, reproductive health, and

adolescent pregnancy issues. OPA also administers two grant programs, the national Family Planning Program, authorized under Title X of the Public Health

Service Act (PHSA) and the Adolescent Family Life Program, authorized under Title

XX of the PHSA. In Fiscal year 1999, Title X Family Planning Clinics expect to

serve nearly 5 million persons through a nationwide network of 4,600 clinics. Priority is given to persons from low-income families; services are provided at no cost

to persons at or below the poverty level and on a sliding fee scale up to 250 percent

of the poverty level. Many of CDC’s NBCCEDP programs collaborate with Title X

programs and share information with Title XX demonstration projects on a local

level. Certain Breast and Cervical Cancer programs contract with family planning

programs for screening services and some OPA’s Title X programs refer women to

NBCCEDP’s contracted facilities for additional follow-up and diagnostic care when

Pap testing detects abnormalities. These special partnerships are arranged on a

local, State-by-State or program-by-program basis.

Finally, CDC’s Division of Reproductive Health (DRH) is currently examining the

effects of parity (the number of children born alive to a woman) and age at first

birth on risk of invasive cervical cancer. CDC is using data from a population-based,

case-control study of cervical cancer in Costa Rica collected between 1982 and 1984.

Preliminary results suggest that risk of cervical cancer increased with increasing

parity and decreased with increasing age at first birth.

The liaisons for the respective agencies are Nancy C. Lee, M.D., Division Director,

CDC/NCCDPHP/DCPC; Marilyn H. Gaston, M.D., Associate Administrator, DHHS/

HRSA/BPHC; and Thomas Kring, Deputy Director, DHHS/OS/OPHS/OPA.

Question: 7A. What is the amount of research dollars spent by CDC on HPV as

compared to the virus that causes AIDS? 7B. How many women die annually in the

United States from cervical cancer? 7C. How many women die annually in the

United States from HIV-related illnesses?

Answer: A. During FY98, CDC spent approximately $1.25 million dollars for research on HPV and $41.356 million for research on HIV and AIDS.

B. In 1996, the latest year for which complete data is available, 4,552 women died

of cervical cancer in the United States (CDC, National Center for Health Statistics,

Deaths: Final Data 1996, National Vital Statistics Reports; Volume 47, Number 29).

C. In 1996, the latest year for which complete data is available, there were 5,853

HIV-related deaths among women in the United States (CDC, National Center for

Health Statistics, Deaths: Final Data 1996, National Vital Statistics Reports; Volume 47, Number 29).
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