NEWSLETTER OF THE NCI DIVISION OF CANCER PREVENTION 1

The ultimate aim of

early detection is to

decrease cancer mortality. In the Division

of Cancer Prevention,

our early detection

goal is to develop and test

early detection methods to achieve that aim.

Further, we do so with controlled clinical

trials that meet the most stringent criteria

for quality of evidence as articulated by the

U.S. Preventive Services Task Force (USPSTF). The USPSTF is an expert group that

periodically reviews early detection research

and provides clinical guidelines for the medical profession and the public. Their first

and strongest level of evidence is “Evidence

obtained from at least one properly randomized controlled trial.”

In DCP, several research groups work on

such trials. The design, management, and

analysis of early detection clinical trials falls

to the Early Detection and Biometry

Research Groups. The Organ Systems

Research Groups add medical expertise to

research teams focused on early detection,

and the Cancer Biomarkers Research Group

utilizes new technologies for biomarker

development and validation that may provide better means in the future for risk 

prediction and detection of early neoplasia.

Biorepository maintenance and research is

done in collaboration with NCI’s. Division

of Cancer Epidemiology and Genetics.

Prostate, lung, colorectal, and ovarian

cancers together account for about half of

all cancers diagnosed and half of all cancer

deaths in the United States each year. DCP’s

Early Detection Research Group is managing a large-scale randomized trial evaluating

prostate-specific antigen, digital rectal exam,

chest x-ray, sigmoidoscopy, CA125 tumor

Early Detection Research PETER GREENWALD

DIRECTOR, DIVISION OF CANCER PREVENTION

One objective of cancer prevention is to decrease the incidence of invasive cancers by

identifying people at high risk and then intervening with preventive strategies in such

individuals. High risk may be due to a prior cancer, hereditary mutations (e.g., BRCA1

in breast, APC in colon), other factors (e.g., smoking), or hormonal stimulation. Persons in

these population-based groups are at higher risk than average but (except for high penetrance

germ-line mutations) have a lifetime risk of less than one in four for any specific cancer. One

approach to assessing individualized risk is to examine people for the changes associated with

the carcinogenic process or perhaps even the earliest stages of invasive cancer. Early attempts at

determining personal risk have often involved the use of imaging techniques; such as chest xrays which is one of the techniques used in the Prostate, Lung, Colorectal and Ovarian Cancer

Screening Trial (PLCO).

continued on page 5

IN THIS ISSUE

Early Detection Research 1

Molecular Diagnosis and the Early

Detection Research Network 1 

Screening for Cancer 2

The ALTS Trial 3

PreventionPOST Credits 3

Cancer Prevention Fellowship Program 4

DCP Trials Reach Major Milestone 6

History of Cancer Prevention:

George Papanicolaou 7

Annual Lecture on Cancer Prevention 9

DCP Awardees 9

Highlights on Conferences, Workshops,

and Retreats 10

Transitions 11

Endpoints 12

January 2002

V O L UME 4/ISSUE 1

NEWSLETTER OF THE NCI DIVISION

OF CANCER PREVENTION

PreventionPOST

Molecular Diagnosis and the Early Detection Research Network (EDRN)

R ON LUBET AND LORA KUTKAT

continued on page 2
T

he diagnosis of the cancer is being pushed back in time.

Smaller and smaller cancers are being found through

screening and early detection. This backward push is

reflected in national survival and mortality statistics and types

of specimens submitted by surgeons. 

Carcinoma in situ of the uterine cervix is now three times

more common than its invasive counterpart. As a result, mortality for this disease in the US has decreased significantly. In

the early 1970s, most reported series of breast cancers included only a small proportion of in-situ ductal carcinomas, usually less than 5%. Currently, in some publications the frequency of ductal carcinoma in situ approaches 30%.

Screening has literally revealed a new disease of the breast.

The mortality for breast cancer has consistently decreased for

the last 10 years and most likely will continue to decrease.

For prostate, the systematic use of PSA (prostate specific antigen) testing in men over 50 has resulted in the increased

detection of prostate intraepithelial neoplasia and early prostatic cancer. For colon, the systematic excision of adenomas

found through endoscopy has contributed to a reduction in the

incidence of invasive carcinomas. If we could routinely detect

and treat these small tumors, we would for practical purposes

be able to eliminate the mortality from the vast majority of

invasive cancers without even knowing their cause.

There is reasonable expectation that molecular biology will

eventually provide new tools for screening and early detection.

These tools should have the ability to detect very small cancers

including those present in poorly accessible anatomic sites,

such as prostate and ovary. This expectation frames the work

of the Early Detection Research Network whose mission is to

discover and validate biomarkers for early detection.

At the present time, more traditional forms of screening

continue to contribute to success in our fight against cancer.

This has been recognized by DCP in its long range planning

and program development. The Division recognized that 

previous successes, for instance the HIP trial for mammogra2 PreventionPost J ANUARY 2002

markers, and transvaginal ultrasound to see if these screening

tests will reduce mortality from these four cancers. Known as

the PLCO Cancer Screening Trial, this landmark study

includes about 155,000 screened participants and usual care

controls at ten centers. The trial will go through 2012.

Newer, promising early detection methods are also being

studied:

• Low-dose spiral (or helical) computed tomography (CT)

has been shown to be more sensitive than chest x-ray in

detection of small lung lesions. However, the relative 

benefits and harms of spiral CT screening for lung cancer have not been determined. Randomized clinical trials in the 1970s showed that chest x-ray and sputum

cytology could improve detection of resectable lung

cancers, but did not show a decrease in mortality.

PLCO investigators showed the feasibility of a randomized, spiral CT lung screening trial by screening 3373

high risk people. A definitive trial, the National Cancer

Screening Trial, will be conducted jointly by PLCO

investigators and the American College of Radiology

Imaging Network.

• Dr. David Ahlquist and his colleagues at the Mayo Clinic

have explored the feasibility of a stool assay panel of

selected DNA alterations in distinguishing persons with

colorectal cancer from people with polyps or without

lesions. Analyzable human DNA was recovered form the

stools of all 61 persons tested and the method was shown

to hold promise as a stool screening approach for colorectal neoplasia. A larger study is proposed.

• Drs. Lance Liotta, chief of NCI’s Laboratory of

Pathology, and Emanuel Petricoin of the Food and Drug

Administration are studying proteomic patterns of

serum from patients with ovarian or prostate cancer,

benign conditions, or no prostatic or ovarian disease to

see if low-molecular-weight serum proteins, analyzed by

an artificial intelligence recognition algorithm, can be

used to distinguish these three groups. Initial studies

show promise of this technique.

Randomized clinical trials are an essential step in determining

the effectiveness of new technologies for reducing cancer 

mortality. DCP puts a high priority on this type of research. ■

Early Detection Research continued from page 1

Screening for Cancer DONALD E HENSON

continued on page 8
IN MEMORIUM

The ALTS Trial

KATHLEEN FOSTER

DCP suffered a great loss when

Carolyn Clifford, Ph.D., passed

away on May 31, 2001. Carolyn

worked at NCI for the past 17

years and her research focused

on the importance of diet in cancer prevention. At the time of

her death she was co-acting

Deputy Director of the Division

of Cancer Prevention. In the past

few years, she served as acting

Chief of the Nutrition Research

Group and acting Chief of the

Prostate and Urologic Cancers

Research Group. She was active

in nutrition research across the

NIH community and was a member of the NIH Nutrition

Coordinating Committee and of

the Women’s Health Initiative.

Her milestone contributions to

the field of cancer prevention

and dedication to DCP will not be

forgotten.

Carolyn Clifford, Ph.D.

EDITORIAL GROUP

Doug Weed 

(Editor-in-Chief), 

Garça Dores, 

Susan Perkins, 

Dee Sullivan

DISTRIBUTION

GROUP

Kathleen Foster, 

Judy Smith, 

Susan Winer

Terry Cornelison

WEB GROUP

Kara Smigel-Croker

Lora Kutkat

PRINTING GROUP

Jennifer Flach,

Don Henson, 

Ron Lubet

PreventionPOST

DCP Newsletter Project Team

NEWSLETTER OF THE NCI DIVISION OF CANCER PREVENTION 3

T

he ASCUS/LSIL Triage Study (ALTS) was designed to

resolve questions regarding the best possible management of low-grade and equivocal

cytologic abnormalities of the cervix

found on Pap tests. These Pap test

results, referred to as ASCUS (Atypical

Squamous Cells of Undetermined

Significance) and LSIL (Low-Grade

Squamous Intraepithelial Lesions),

though considered mildly abnormal or

ambiguous, account for millions of cases

of abnormal Pap smears in the United

States each year. In the majority of

cases, finds of ASCUS and LSIL will

resolve without treatment. However,

occasionally they indicate a pre-cancerous condition, or rarely, cancer. This

medical management dilemma indicated

a need to develop effective colposcopy

triage strategies that would identify

patients with clinically significant disease while avoiding excessive follow-up evaluation for those

determined to be low risk. 

ALTS originally evolved from a joint workshop held in

1993 by ACOG (American College of Obstetricians and

Gynecologists) and NCI, which mandated a trial to shed light

on this clinical problem. Organized and funded by the NCI

and administered by the Division of Cancer Prevention in collaboration with the Division of Cancer Epidemiology and

Genetics, this randomized trial enrolled

5,000 women with a recent diagnosis of

ASCUS or LSIL. Dr. Diane Solomon

(DCP) and Dr. Mark Schiffman served

as Co-Project Officers for the study.

Four clinical centers in geographically

diverse regions around the country followed the cohort for a total of two

years. The trial consisted of three management arms. The first arm utilized

immediate colposcopy (magnification of

the cervix and biopsy of any clinical relevant lesions). The second arm involved

HPV (Human Papillomavirus) triage,

using colposcopy only if there is a positive HPV result. The third arm was a

conservative management arm, with

routine follow up cytology. If HSIL

(High-Grade Squamous Intraepithelial

Lesion) or worse was seen, triage to colposcopy was indicated.

ALTS has also compared the efficacy of different strategies in

the early detection of high-grade lesions. 

Conclusions reached are threefold. For women with

ASCUS testing for HPV is a highly sensitive way of detecting

the underlying abnormalities that are at risk of progressing to

continued on page 7
In July the Cancer Prevention Research Training Merit Awards were

presented to Lisa Colbert, Lori Beth Dixon, Ann O’Mara and Rachael

Stolzenberg-Solomon. This is the second year that the Cancer

Prevention Fellowship Program has awarded these certificates for

outstanding performance.

David Berrigan, a third year fellow, won the Cooper Institute 2001

Research Conference Paper Competition.

Qing Lan, a first year fellow, was awarded the Scholar-in-Training

Award at the American Association for Cancer Research at the

March meeting in New Orleans, LA. In addition, she was awarded the

Outstanding Research Paper by a Fellow in the Division of Cancer

Epidemiology and Genetics for the year 2001. ■

ON THE PERSONAL SIDE

A W ARDS

Best wishes go to Kerri McGowan-Lowery and her husband, Doug, on

the birth of their daughter, Morgan Grace. ■

CAREER MOVES

The Cancer Prevention Fellowship Program had a great

number of applicants to the program – 88 applications

for the 2002 entry into the fellowship program. This is

an increase of 37% over last year. The newest feature of

the program is a career track in the Ethics of Public

Health and Prevention. 20 applicants applied in response

to this new career track.

Interviews for the Cancer Prevention Fellowship

Program Class of 2002 were held on October 31,

November 1 and 2. 30 applicants were interviewed and

selected for the program to begin in July 2002. As a special feature former fellows give lectures on their career

and research and how the fellowship program helped

them attain their goals. This year the lecturers were:

Corinne G. Husten,, MD, MPH, Branch Chief,

Epidemiology Branch, Office of Smoking and Health,

Centers for Disease Control and Prevention in Atlanta

GA; Ellen Velie, PhD, MPH, Assistant Professor,

Department of Epidemiology, Michigan State University,

East Lansing, MI; and Sheila Prindiville, MD, MPH, former Assistant Professor of Medicine, University of

Colorado Health Sciences Center, Denver, CO.

Second year fellows are currently working with preceptors in the following divisions: Division of Cancer

Prevention ; Division of Cancer Control and Population

Sciences; Division of Clinical Sciences; and the Center

for Cancer Research.

First year fellows are getting their MPH at the following schools: Johns Hopkins University’s Bloomberg

School of Public Health, Harvard University, New York

Medical College and the University of North Carolina at

Chapel Hill.

The Cancer Prevention Fellowship Program suite in

EPS, T41 is undergoing major renovations. Several staff

members have relocated to the adjoining building in

EPN Suite 3109. Dr. Shine Chang, an Epidemiologist,

joined the program to spearhead program evaluation

efforts. She came from the M. D. Anderson Cancer

Center in Houston, Texas. ■

At the Forefront of Training SUSAN WINER

Cancer Prevention Research Training Merit Awardees with Steve Husting

and Doug Weed.

4 PreventionPost J ANUARY 2002

RECRUITMENT FOR 2003

As the new fiscal year has begun,

the recruitment effort is in full

swing for the Cancer Prevention

Fellowship Program. In conjunction

with the Office of Communications,

NCI, the fellowship program will be

represented at more than 10 scientific meetings. In Spring of 2002,

the office will travel to the Johns

Hopkins University’s Bloomberg

School of Public Health’s career

fair and a career fair at Harvard

University. ■

Lisa H. Colbert, PhD, MPH has

joined the National Institute on

Aging as a Senior Research

Fellow; Rita Misra, PhD, MPH

joined the Division of Cancer

Treatment and Diagnosis, NCI,

as a Biologist; Ann O’Mara, PhD,

MPH joined the Division of

Cancer Prevention, NCI as a

Program Director; and Heng Xie,

MD, MPH joined the Division of

Cancer Treatment and Diagnosis

as a Program Director.

Congratulations and best wishes

on their continued success. ■

C ANCER PREVENTION FELLOWSHIP PROGRAM 
Alternatively, one can identify molecular changes associated with cancer or the carcinogenic process. This is the

primary focus of the EDRN. The explosion in the field of

molecular biology in the past 20 years has helped to define

many of the changes in cells that contribute to the carcinogenic process. These include 1) changes in DNA, e.g.,

mutations, recombination, and amplification or deletion of

genes; 2) altered expression of specific genes resulting in

altered expression of the proteins they encode; and 3) posttranslational modifications, including phosphorylation and

prenylation, which can alter the activity of proteins.

Changes in these classes are seen in all cancers. Prostate

specific antigen (PSA), for instance, is a protein that is

expressed at higher levels in tumors than normal epithelium. We will briefly discuss two, of many, molecular biology approaches.

Determination of DNA methylation patterns in lesions 

and serum

Most cancers have various genes with altered expression

when compared with control tissues. One way of decreasing

gene expression is through decreasing the rate at which the

gene is transcribed (made into RNA). Perhaps the most

common manner of achieving decreased transcription is by

methylation of the DNA of the gene. In fact, altered methylation patterns are common and early events in most cancers. The tools of molecular biology, like methylation-specific endonucleases and methylation-specific PCR primers,

allow detection within a mixture of cells of some cells with

methylation at specific sites. If methylation of specific genes

is associated with cancer, scientists can examine a mixture of

cells from the individual and determine whether neoplastic

cells are present in the mixture. In a study looking for methylation of the APC gene (K. Kawakami, et al., JNCI 92,

1805-1811, 2000) in patients with esophageal adenocarcinoma (EGA), methylation was observed in 92% of samples

with EGA, in 40% of samples from patients with Barrett

esophagus (a preinvasive lesion which may be a precursor to

EGA), but in 0% of normal control tissues. This methylation pattern could be used to support a diagnosis of EGA

but might also help identify the individuals with Barrett

esophagus at highest risk for progression to EGA. These

persons would be particularly appropriate for chemopreventive intervention. This approach appears applicable to many

of the major epithelial cancers, including lung cancer.

Proteomics: Altered protein expression in tumors and 

body fluids

Differences in expression of proteins are associated with all

tumors. Some may be directly associated with the carcinogenic process, whereas others may be secondary bystander

effects. Regardless, these altered protein levels may be diagnostic, prognostic or risk markers. Recent improvements in

2-dimensional gel electrophoresis and SELDI (Surface

Enhanced Laser Desorption/Ionization) and MALDI

(Matrix Assisted Laser Desorption/Ionization) technologies,

which allow the separation of proteins based on their ability to bind to surfaces with specific chemical characteristics,

have made possible the simultaneous examination of scores

or even hundreds of proteins. These methods raise the possibility that some combination of changes will achieve far

greater accuracy than any single marker. Assessment of certain serum proteins (prostatin and carcinoembryonic antigen) appears to allow detection of early ovarian cancer

with both moderate sensitivity and specificity (S.C. Mok, et

al., JNCI 83, 1458-1464, 2001). However, even this degree

of accuracy is probably not sufficient to warrant random

screening of the female population (G.B. Mills, et al., JNCI

93, 1437-1439, 2001). Similarly, a study employing workers exposed to benzidine showed that measurement of two

markers, a specific protein (P-300) and DNA copy number,

in cells found in the urine could identify most individuals

with cancer (G.P. Hemstreet, et al., JNCI 93,427-436,

2001). These markers could also predict individuals at high

risk of cancer 6 to 12 months prior to clinical diagnosis,

thereby making this group amenable to prevention strategies. Thus, some of these proteomic approaches may prove

to be particularly useful for non-invasive determination of

lesions or risk. 

Cancer detection and risk evaluation through molecularbased means, coupled with preventive interventions, are

key components in DCP quest to reduce cancer incidence. 

For more information: http://edrn.nci.nih.gov ■

NEWSLETTER OF THE NCI DIVISION OF CANCER PREVENTION 5

Molecular Diagnosis continued from page 1
T

he Division of Cancer Prevention sponsors only a few

large-scale screening and prevention trials, but each of

these major studies will answer crucial medical 

questions. Three of these large studies have reached major

milestones since the last issue of the Prevention Post.

The Selenium and Vitamin E Cancer Prevention Trial

(SELECT), a study for the prevention of prostate cancer,

opened its doors with a media blitz on July 24 and has begun

randomizing participants. The Prostate, Lung, Colorectal,

and Ovarian Cancer Screening Trial (PLCO) and the Study

of Tamoxifen and Raloxifene, major DCP clinical trials

aimed at cancer screening and breast cancer prevention

respectively, have reached major milestones in recruitment. 

SELECT

On July 24, a call went out

for healthy men age 55 and

older to join the largest-ever

prostate cancer prevention

study, launched by NCI and a network of researchers known as

the Southwest Oncology Group (SWOG). The Selenium and

Vitamin E Cancer Prevention Trial, or SELECT, will determine if

these two dietary supplements can protect against prostate cancer,

the most common form of cancer, after skin cancer, in men. Out

of a total of 32,400 men needed for the study 7,348 had joined

SELECT as of January 28, 2002.

More than 400 sites in the United States, Puerto Rico, and

Canada are recruiting participants for SELECT, which will take

up to 12 years to complete. SELECT is the first study designed

to look specifically at the effects of vitamin E and selenium,

both separately and together, in preventing prostate cancer.

“We are looking for quite a few good men to join SELECT

because it is an incredibly important prostate cancer prevention study,” said Lori Minasian, MD, chief of the Community

Oncology and Prevention Trials Research Group in DCP.

“Previous research with vitamin E and selenium—in studies

focused on other kinds of cancer—suggested that these nutrients might prevent prostate cancer. SELECT is focused on

prostate cancer and, when the study is finished, we will know

for sure whether these supplements can prevent the disease.”

Nearly 76 million people saw television news stories about

SELECT and the trial was featured in 49 of 50 major media

markets in the United States in either radio, print, or TV

coverage. NCI is following up on how this unprecedented

news interest in a prevention trial will affect randomization

and recruitment to see if any methods can be borrowed to

assist recruitment for other important prevention trials.

For more information: http://cancer.gov/select 

PLCO

In late July, the last of nearly

155,000 men and women

joined the PLCO, marking

the end of the recruitment

phase of the trial. The 10

PLCO centers in the trial began randomizing participants in

1995 to determine if certain cancer screening practices reduce

the number of deaths from these cancers. Tests include digital

rectal exam and a blood test for prostate specific antigen to

test for prostate cancer, chest X ray for lung cancer, flexible

sigmoidoscopy for colorectal cancer, and transvaginal ultrasound and a blood test for the tumor marker known as CA125 to detect ovarian cancer.

PLCO will continue to collect and analyze essential health

data from participants, who are randomized to usual care or

to a screening group that receives screening tests for five years

and then are followed for up to 10 more years. 

“A fundamental mission of the NCI is to reduce cancer

death rates,” said John Gohagan, PhD., chief of DCP’s Early

Detection Research Group and head of the PLCO. The four

cancers targeted in the PLCO together account for 48 percent

of all cancers diagnosed and 49 percent of all cancer deaths in

the United States. A success for any of the tests could make a

significant difference in cancer mortality.

For more information: http://cancer.gov/plco

STAR

In late summer, STAR reached the

halfway point of recruiting 22,000 postmenopausal women at increased risk for

developing breast cancer to this crucial

prevention study. STAR is designed to

determine whether the osteoporosis prevention and treatment drug raloxifene

(Evista) is as effective as tamoxifen (Nolvadex) in reducing

breast cancer risk. STAR is carried out by the National Surgical

Adjuvant Breast and Bowel Project (NSABP).

As of December 31, 2001, 12,117 women had joined the

trial out of more than 58,000 women who were eligible for

the trial based on increased risk of breast cancer. More than

103,000 women have gone through the breast cancer risk

assessment process offered by STAR investigators to deter6 PreventionPost J ANUARY 2002

DCP Trials Reach Major Milestones

KARA SMIGEL CROKER
NEWSLETTER OF THE NCI DIVISION OF CANCER PREVENTION 7

DCP Trials continued from page 6

mine their eligibility for the study. “All women are at risk for

breast cancer, whether they are eligible for STAR or not,”

noted Leslie Ford, M.D., associate director for clinical

research at DCP. “STAR is designed for a particularly highrisk group.”

To join the trial, women must have a risk of breast cancer

that is equivalent to a 60-year old woman: 17 of every 1,000

would develop breast cancer within five years. More than half

the women who have joined STAR have a risk for breast cancer that is higher than 32 per 1,000, nearly double the minimum risk.

Additionally, STAR is doing a better job of attracting

minority women than previous breast cancer prevention studies: In only the first two years of STAR, 30% more minority

women have joined STAR as had joined the Breast Cancer

Prevention Trial (BCPT), the predecessor study to STAR, over

the life of that trial. The BCPT had a total of 486 minority

women on the 13,000-woman trial, compared with 692

minority women on STAR so far.

For more information: http://cancer.gov/star ■

cervical cancer, and need an immediate intervention. Thus HPV

testing is a viable option for the management of this abnormality. Secondly HPV testing is not useful for women with a Pap

test diagnosis of LSIL. Over 80% of the women with LSIL tested positive for HPV. This high prevalence limits the usefulness

of HPV testing in the management of LSIL. Finally it was

noted that expert interpretations of Pap tests vary substantially

in interpreting both thin-layer Pap test and histologic biopsies;

agreement/ reproducibility was only moderate. Therefore this

variability should be taken into account when using these interpretations, and in developing standards of practice.

Many more analyses of the ALTS data are in process and 

targeted for release over the next three years. Plans are underway for more than 30 subsequent publications analyzing 

longitudinal follow-up of the study cohort. These publications

will examine topics such as sensitivity of the management arms

for ASCUS and LSIL, cost utility, different perspectives on the

risk of CIN 3, and issues related to HPV follow-up and 

treatment. Most importantly study data is being actively 

considered in the development of new consensus guidelines for

the management of women with an abnormal Pap test.

Further information on this study can be found at the ALTS

web site, http://cancer.gov/prevention/alts.html

An additional outcome was the contribution that the ALTS

trial has made by informing the discussion that took place at

the Bethesda 2001 Conference. This NCI workshop held in

May 2001 reviewed issues regarding the terminology and

reporting of cervical cytology. As a result of discussions held

between cytopathologists, cytotechnologists, clinicians and

patient advocates, revisions were made to the Bethesda reporting system. The final 2001 Bethesda terminology can be found

on their web site, http://bethesda2001.cancer.gov. ■

ALTS Trial continued from page 3

George Papanicolaou, M.D., Ph.D.

1883 - 1962

DOUG WEED

The “Pap” smear, named for Dr. George

Papanicolaou, emerged from the work of two

Cornell University researchers, Dr. “Pap” and

his colleague, Dr. Herbert Traut, a gynecologic

pathologist. In 1943, they jointly published

“Diagnosis of Uterine Cancer by Vaginal

Smear” showing that women with cancer exhibited abnormal cells. Papanicolaou had first

observed the phenomenon twenty years earlier, although he had originally set out to use cytological changes in vaginal discharges to measure normal cyclical changes in the ovulatory cycles of guinea pigs

and other mammals. The “Pap” smear is now an integral part of

early detection efforts worldwide. 

Papanicolaou was born in Greece in 1883 and attended medical

school at the University of Athens, graduating in 1904. He served in

the Greek army medical corps and spent a year caring for lepers in a

colony near his hometown. He left Greece to pursue more education in Munich, Germany where he received a Ph.D. in 1910 at the

Zoological Institute in Munich. In 1913, Papanicolaou and his wife,

Mary, arrived in the United States; both found jobs at Cornell

Medical School in New York.

Papanicolaou’s work in exfoliative cytology was not limited to

the detection of cervical cancer. In 1954, he published a definitive

text, “Atlas of Exfoliative Cytology” in which he extended his techniques to the respiratory, urinary, and upper gastrointestinal tracts as

well as the breast.

He died in 1962, a few months after becoming director of the

Papanicolaou Cancer Research Institute in Miami.

HISTORY OF CANCER PREVENTION
phy and the fecal occult blood test for colon cancer, justified

further screening trials. Thus, it laid plans for randomized trials designed to provide unequivocal evidence of mortality

reduction using different modalities of screening for a variety

of major cancers. As a result, the PLCO, a major national initiative, was created to evaluate screening tests for prostate,

lung, colorectum, and ovarian cancer. Started in 1993, the

trial surpassed initial goals by recruiting 155,000 participants

in seven years. Because of its size and complexity, this trial has

been carefully monitored by a Data Safety and Monitoring

Board that meets periodically. Already, potential new trials

have been inspired within the PLCO. They include a study of

low dose spiral computed tomography for the detection of

lung cancer, evaluating the role of aberrant crypt foci in the

pathogenesis of colon cancer, and a special project on virtual

colonoscopy will soon be published.

The Division has not neglected the pediatric population.

Recently completed was a screening study in Canada for neuroblastoma the most common solid malignant tumor occurring in children under 5 year of age. All 476,603 children

born in the province of Quebec during the 5-year period from

May 1989 to April 1994 were eligible for screening at 3

weeks and 6 months of age. At three weeks, 425,816 children

were screened and at 6 months 349,706 were screened.

Supported by DCP and conducted by investigators from the

University of Minnesota and Canada, this study was possible

because Quebec maintains a province wide follow-up on all

children. Control populations used during the study included

the state of Minnesota and the province of Ontario.

Neuroblastoma occurs in two forms, a benign non-fatal form

found early in life and a virulent form that usually appears a

little later. Both forms are thought to arise in utero. Screening

increased the incidence of the benign form without decreasing

the incidence of the more virulent form. Results from this trial

will undoubtedly influence other countries contemplating

screening programs for neuroblastoma.

DCP’s leadership was again evident in the ALTS trial, one

of the most significant clinical studies of cervical cancer ever

undertaken. This randomized trial was designed to deal with

the issues of patient management following an equivocal

screening result. Women entering the trial already had an

abnormal pap test. In this randomized triage trial, molecular

testing was done for the different types of human papilloma

virus, the alleged cause of cervical cancer. It was also the first

trial designed to reveal the natural history of abnormal lesions

of the uterine cervix. The outcome of this trial will influence

our interpretation of cervical cancer screening and guide

patient management for many years. Further, the design of

this trial can serve as a model for all future clinical trials that

triage the management of preinvasive lesions.

Sloan Kettering is conducting a study on the feasibility of a

randomized trial on colonoscopy screening. The trial is based

on the novel concept, based on previous studies, that a single

screen around age 60 would reduce the incidence of colon

cancer by 60%-75%. In the study, subjects receive an initial

colonoscopy and after 5 to10 years a second colonoscopy to

test the hypothesis. Control subjects receive usual care. The

purpose of the study is to determine whether subjects can be

recruited into such a trial and remain compliant during follow-up as well as to determine the psychosocial factors that

influence compliance. This study represents a novel approach

to the early detection of colon cancer and the results may lead

to a change in screening recommendations.

As the Division continues to launch innovative randomized

trials designed to test new technology, more effective and proven

screening programs will find their way into medical practice. ■

Screening for Cancer continued from page 2

8 PreventionPost J ANUARY 2002

DCP home base: Executive Plaza 
Annual Lecture on Cancer Prevention

SUSAN WINER

NEWSLETTER OF THE NCI DIVISION OF CANCER PREVENTION 9

The Division of Cancer

Prevention would like to congratulate Dr. Diane Solomon

(BGCRG) who was recognized

with the Maurice Goldblatt

Award in May 2001, the highest

award given by the International

Academy of Cytology, for her

outstanding work in cervical

cancer screening. She also

received an NCI Merit Award in September 2001 for

exemplary scientific leadership and technical management of the ASCUS/LSIL Triage Study. 

Dr. Sudhir Srivastava (CBRG) was

selected to receive the Department

of Health and Human Services

(DHHS) Asian Pacific Network

Special Award in May 2001, for

advancing the interests and

addressing issues of Asian Pacific

Americans within the U.S. DHHS

and of the general Asian Pacific

Islander community. 

In September 2001 the Nutritional Sciences Program at

the University of Missouri-Columbia awarded Dr. John

Milner (NSRG) The Boyd O’Dell Lecturer Award for

excellence in nutrition. 

Dr. Jaye Viner (GOCRG) received an NCI

Commendation Medal in September 2001 for exceptional and sustained commitment to persons at risk for cancer and to the mission of the National Cancer Institute. 

Drs. Donald Henson (CBRG),

Harold Seifried (NSRG), Sudhir

Srivastava (CBRG), Claudette

Varricchio (COPTRG), and

Carolyn Clifford were honored

with a Special NCI TransDivisional Award in September

2001 for completion of the Best

Practices Document-an online

manual for NCI staff on grant

review, funding and administration. Kudos to all!

DCP AWARDEES

On August 2nd , the Annual Lecture on Cancer

Prevention was held in Lister Hill auditorium on the

NIH main campus. After opening remarks, Doug

Weed, Director of the Cancer Prevention Fellowship Program,

introduced the speaker, Frederick P. Li, MD. Dr. Li is Vice

Chair for Population Sciences, Department of Adult Oncology,

Dana Farber/Harvard Cancer Center in Boston,

Massachusetts. In addition, he is Professor of Clinical Cancer

Epidemiology at the Harvard School of Public Health and

Professor of Medicine at the Harvard Medical School.

The title of Dr. Li’s lecture was Identification and Care of

Those at Highest Risk of Cancer.

As part of the introduction, Dr. Li was

presented with a special hand calligraphy

certificate in appreciation of his participation in the lecture series.

After the lecture, Dr. Li answered questions from the assembled large audience that included Cancer

Prevention Fellows, NCI/Irish Consortium researchers and

interested researchers at the NIH. A reception was held in the

lobby of Lister Hill. ■

Diane Solomon

Sudhir Srivastava

Harold Seifried

Jaye Viner and Richard Klausner
1 0 PreventionPost J ANUARY 2002

DCP maintains a primary commitment to improving public health by advancing biomedical science

and strengthening preventive medicine. One

approach used to accomplish this goal includes sponsoring

and coordinating scientific and administrative workshops

and seminars. Such

meetings provide a

forum for galvanizing

scientific ideas and

enhancing collaborations

among government,

academia, and industry.

Several activities of this

nature were presented

recently.

Young Kim,

Nutritional Sciences

Research Group

(NSRG), coordinated a

workshop titled

“Nutrition and

Genomics” on June 18,

2001. The workshop

was a joint NCI,

USDA, and American

Society for Nutritional Sciences effort to raise awareness

of the linkages between nutrients and genes as determinants of growth, development, and disease risk. The

workshop produced a number of substantive recommendations to promote the use of new and innovative gene

technologies in nutritional science.

Sharon Ross, also from NSRG, coordinated a three-day

workshop in August, “Diet, DNA Methylation Processes

and Health” to enhance knowledge and understanding of

the role of dietary factors in DNA methylation processes.

Attendees included basic scientists, clinicians, epidemiologists, and nutritional scientists from the nutrition community. The workshop was a collaborative effort between

federal sponsors, American Society for Nutritional

Sciences, and the International Life Sciences Institute.

In August, the Cancer Biomarkers Research Group

(CBRG) presented “Nanotechnology in Early Detection

of Cancer” in collaboration with the National Institute of

Standards and Technology. The goal of this workshop

was to assemble experts

in the field to discuss

and explore potential

utility of nanotechnology in early detection

and prevention programs. CBRG also convened the “Second

Annual Early Detection

Research Network

Scientific Workshop” in

Seattle in mid-October. 

The Second Annual

Program Operations

Staff (POS) Retreat was

held on September 24-

25 at the Governor

Calvert House in

Annapolis, MD. Dr.

Rhey Palmer, facilitator, guided the staff through Conflict Mediation-Self

Assessment to enhance understanding of the nature of

conflict and conflict resolution. Linda Wong was reelected project team leader for the upcoming year;

Linda Grey will serve as alternate. 

Upcoming workshops include the second annual Site

Coordinator’s Opportunity for Research Excellence

(SCORE) scheduled for March 2002. The purpose of this

meeting is to convene clinical trials coordinators of DCP

contract studies and DCP program staff to discuss issues

related to the conduct of the trials. Ellen Richmond

(Gastrointestinal and Other Cancers Research Group) is

coordinating this effort. ■

Highlight on Conferences, Workshops, Retreats

JUDITH J. SMITH

Program operation staff gather in Annapolis, Maryland
We would like you to join us in welcoming new staff to DCP:

Doris Browne, M.D., M.P.H.

Program Director, Breast and

Gynecologic Cancers Research

Group from Medical Research

and Development

Headquarters, U.S. Army

Medical Research Command

Emilia Richichi, Ph.D. 

Program Specialist,

Chemopreventive Agent

Development Research Group

from the World Bank Group

Darnell Proffitt 

Program Operations Staff,

Office of the Associate

Director from Office of 

Space and Facilities

Management, NCI

Shine Chang, Ph.D., M.P.H.

Expert Epidemiologist, Office

of Preventive Oncology from

M.D. Anderson Cancer Center. 

Lanette West-Johnson

Administrative and Personnel

Technician, DCP ARC from

Advanced Technology 

Center, NCI

JENNIFER FLACH

Good Luck!

Yvonne Grant, Nutrition Research Group, in her new 

position at DCCPS.

Barry Portnoy, Office of the Deputy Director, in his new

position at the NIH Office of Disease Prevention.

Shelia Stempler, Office of the Director, in her retirement

in Boynton Beach, Florida.

D’Annie Gunter, Protocol Information Office, in her new

position in the Public Health Service.

Andrew Hruszkewycz, Prostate and Urologic Cancers

Research Group, in his new endeavor.

Twanda Adams, Cancer Biomarkers Research Group, in

her new position in the Cancer Information Service.

Nikki Herman, DCP ARC, in her new position at the

National Oceanographic & Atmospheric Administration,

Department of Commerce.

TRANSITIONS

CONGRATULATIONS!

Congratulations to Howard Parnes, M.D., named Chief of

the Prostate and Urologic Cancers Research Group.

Barry Portnoy and Peter Greenwald

Shelia Stempler and Peter Greenwald

DCP says farewell to Shelia Stempler

NEWSLETTER OF THE NCI DIVISION OF CANCER PREVENTION 1 1
1 2 PreventionPost J ANUARY 2002

PreventionPOST

Newsletter of the Division of Cancer Prevention

National Cancer Institute

Executive Plaza South, Suite T-41

6130 Executive Boulevard, MSC-7105

Bethesda, Maryland 20892-7105

Several months ago, we sent a survey to

all DCP staff and Prevention Fellows

with several open-ended questions

about the PreventionPost. Simple questions like: “What do you like about it?

What do you not like about it? Is it 

useful? What would you add to it? Are

there some themes you might recommend to us? 

We hope that the person who responded is happy with

the changes we made. Just kidding. Overall, we had a 

not-so-impressive 25% response rate, but the comments and

suggestions we received were helpful and largely constructive. We were pleased with the positive responses and we

pored over the more critical comments to find ways to

improve. Here are some of the changes that we have made

ENDPOINTS

Survey Says... DOUGLAS L. WEED

Editor-in-Chief

to date: significant decrease in the number of personal 

questions in the spotlight piece; more focus on DCPsponsored workshops and on the DCP retreats (e.g. the

Program Operations Staff). In addition, we’re moving

towards increasing the scientific content of articles so that

the newsletter will be relevant to a broader readership. 

To those who asked for a more frequent publishing 

schedule, we are sorry. Our all-volunteer team is doing the

best it can. To those who reminded us about the importance of

web-based and electronic versions, we have established a new

web-site subgroup within the team with that responsibility.

I am not sure what to say to the individual who wondered

why anyone outside the Division would care about what’s

going on inside the Division. Thanks again for your interest

in the newsletter. ■

CART OON

GRAÇA DORES

EARLY DETECTION