# Presentation: 404329

## Cancer of the Cervix and Other HPV-related CancersAn Overview

** **
**Herschel W. Lawson, M.D.**
**July, 2006**
**Division of Cancer Prevention and Control**** **
**National Center for Chronic Disease Prevention **
**and Health Promotion**** **

- Cancer of the Cervix and Other HPV-related CancersAn Overview

## Outline

**Surveillance**
**Burden of Cervical Cancer **
**Screening **
**Diagnosis **
**Costs**
**Burden of other HPV related cancers**

## The Most Common Cancers in Women

**Breast**

***Cervix***

**Ovary**

**Endometrium**

**Annual number of cases (thousands)**

***More developed countries***

*** ***

***Less developed countries***

*** ***

**Colon/rectum**

**Lung**

**Stomach**

**Adapted from Parkin et al, Eur J Cancer 37:S4, 2001**

**600**

**0**

**200**

**400**

**200**

**400**

**600**

**Notes:**
IARC slides from Nubia Munoz, Year 2000 IARC

## Cervical Cancer Surveillance

## Cervical Cancer Disease Burden in the U.S. 

- Cervical Cancer Disease Burden in the U.S.

- Two types of cervical cancer
**Squamous cell carcinoma**
**Adenocarcinoma  (20% of all invasive cases) **
- 2002 – 12,085 new cervical cancer cases (NPCR)*
- 2002 –   3,952 cervical cancer deaths (NCHS)#
- 2006 Estimates (American Cancer Society)+
**9,710 new cervical cancer cases **
**3,700 cervical cancer deaths **

***U.S. count includes state cancer registries in the National Program of Cancer Registries that met certain data quality criteria for cancer incidence, and cover approximately 93% of the U.S. population.**
**#****Mortality data are from the National Vital Statistics Surveillance System, NCHS, and cover 100% of the U.S. population (**_[www.cdc.gov/nchs](http://www.cdc.gov/nchs)__)_
**+****Cancer Facts and Figures, 2006; American Cancer Society**

## Age-Adjusted Invasive Cancer Incidence Rates, Among Women, U. S.,  2000

**United States Cancer Statistics: 2000 Incidence; NPCR**

**Notes:**
This slide uses data from the NAACR

## Cervical Cancer Mortality Rates, U.S., 1946-1984

**Source: Program for Improving Clinical Pap Smear Programs and Management, Office of Population Affairs, DHHS, 1987.**

## Invasive Cervical Cancer Incidence and Mortality Rates,* by Race, SEER in US, 1975-2002

*******Rates are per 100,000 and are age-adjusted to the 2000 U.S. standard population.**
**Source:  SEER Cancer Statistics Review, 1975-2002**

**Incidence Black**
**Incidence White**

**Death Black**
**Death White**

## Invasive Cervical Cancer Incidence and Mortality Rates,* by Age Group, SEER in U.S., 1998-2002

***Source:  SEER Cancer Statistics Review, 1975-2002**

**Incidence**
**Death**

## Age-adjusted Cervical Cancer Mortality Rates by State Economic Areas*, All Women, U.S., 1995-1999

**Source: Grauman D., NCI; http://www3.cancer.gov/atlasplus/**
***State Economic Area: One or more socio-economically ****similar counties within a state**

**3.93-6.76**

**3.21-3.93**

**2.53-3.21**

**0.90-2.53**

**Sparse**

## Factors Contributing to Cervical Cancer

**Sources:NIH Consensus Conference**
**Janerich, Connecticut**
**Sung, California**

**Never or**
**Rarely Screened**

**Cytology test abnormal,**
**patient lost to follow-up**

**Cytology test abnormal,**
**mismanaged**

**Rapidly progressive**

**Uncommon cancers**
**difficult to detect**

**5%-10%**

**10%-15%**

**5%-10%**

**9%-12%**

**False negative**
**cytology test**

**10%-15%**

**50%-60%**

**Notes:**
Usually we think of predisposing factors which contribute to cervical cancer incidence (e.g., HPV, sexual activity at an early age, multiple sexual partners, smoking), however, we’ve just identified that the most serious factor contributing to cervical cancer incidence and mortality is lack of screening. 

## Cervical Cancer Screening Methods

- Conventional Cytology
- Sensitivity:  51–88%
- Specificity:  95–98%
- Liquid-based Cytology
- Sensitivity: 61-95%
- Specificity: 78-82%

**Source: Meyers et al., 2000; Nanda, et al., 2000; Belinson, et al., 2001**

## Abnormal Pap Test Results (Bethesda 2001)

**Squamous Cell**
- Atypical squamous cells of undetermined significance (ASC-US)
- Atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)
- Low grade squamous intraepithelial lesion (LSIL)
- High grade squamous intraepithelial lesion (HSIL)
- Squamous Cell Cancer
**Glandular Cell**
- Atypical glandular cells (AGC)
- Adenocarcinoma in situ (AIS)
- Adenocarcinoma

## Cervical Cancer Screening Recommendations

|  | USPSTF
2003 | ACS
2002 | ACOG
2003 |
| --- | --- | --- | --- |
| Age to start | Age 21 or within 3 yrs of sexual activity | Age 21 or within 3 yrs of sexual activity | Age 21 or within 3 yrs of sexual activity |
| Interval
   <30 yr 

    ≥ 30 yr 
 | 

Conv: at least every 3 yrs
 | 
      Conv: 1 yr
      LBC:  2 yr

      2-3 yrs  | 
      1 yr

      2-3 yrs  |

**USPSTF – U.S. Preventive Services Task Force**
**ACS – American Cancer Society**
**ACOG – American College of Obstetricians and Gynecologists**
**Conv – Conventional Cervical Cytology**
**LBC – Liquid-based Cytology**

**Notes:**
Talk about penetration of types of screening.

## Prevalence of Cervical Cancer Screening, National Health Interview Survey, United States, 2000

**Swan J, Breen N, Coates RJ, Rimer BK, Lee NC. Progress in cancer screening practices in the United States: results from the 2000 National Health Interview Survey. Cancer. 2003;97:1528-40.**

| Group | % Pap test
past 3 years |
| --- | --- |
| All women | 82% |
| Insured
     Yes
     No  |   
85%
62% |
| Country of birth
    US born
    Foreign born in U.S. <10 yrs
     | 
83%
61% |
| Race/Ethnicity
    Hispanic
    Non-Hispanic White
    Non – Hispanic Black
    Asian   | 
77%
83%
84%
71% |

## HPV Test – Hybrid Capture 2 (HC2)

**A nucleic acid solution hybridization assay with signal amplification that uses long synthetic RNA probes complementary to the DNA sequence of the 13 high risk HPV types.**
**Easy to perform in clinical practice and amenable to automation **
**The only system approved by FDA**

## FDA Approved Use of HPV Test

**Triage: **
**Hybrid Capture II high risk panel (HC2) for ASC-US Pap test results**
**Primary screening: **
**HC2 as adjunct to Pap test in women 30 years of age and older.  If both tests are negative, next cervical cancer screening should not occur for at least 3 years.**

## Organization Recommendations for HPV DNA Use in Cervical Cancer Screening

|  | USPSTF | ACS | ACOG | ASCCP |
| --- | --- | --- | --- | --- |
| ASC-US triage | Insufficient Evidence | Not addressed | Recommended | Recommended |
| Primary screening with
Pap test | Not addressed | Option | Recommended | Recommended |

**USPSTF – U.S. Preventive Services Task Force**
**ACS – American Cancer Society**
**ACOG – American College of Obstetricians and Gynecologists**
**ASCCP – American Society of Colposcopy and Cytopathology**

## Estimated Annual Abnormal Pap Tests, U.S.

**HSIL**
**300,000**

**CA**
**15,000**

**LSIL**
**1,000,000**

**ASC-US**
**2,000,000**

**Modified from Solomon, D., ALTS Trial, 2002; National Cancer Institute**

## Evaluation of an Abnormal Pap Test

**Repeat cytology **
**HPV DNA test with HC 2 as indicated**
**Vaginal and cervical inspection**
**Colposcopy with directed biopsy**
**Endocervical curettage**
**Bimanual pelvic examination**

## Based on estimated incidence rates in 2000, in 2000 $US

**Modified from Chesson et al. Perspectives on Sexual and Reproductive Health 2004, 36(1): 11-19**
**Weinstock et al. Perspectives on Sexual and Reproductive Health 2004, 36(1): 6-10. **

**Based on estimated incidence rates in 2000, in 2000 $US**

## 90%

**Modified from Chesson et al. Perspectives on Sexual and Reproductive Health 2004, 36(1): 11-19)**

**90%**

**6%**

**4%**

## Cancers Attributable to Infection with Oncogenic HPV Types, U.S., 2002

| Site | Total Cancers* | % Estimated HPV Attributable Fraction+  |
| --- | --- | --- |
| Cervix | 12,085 | 100 |
| Anus |   3,703 |   85 |
| Vulva/Vagina |   4,480 |   40 |
| Penis |     985 |   40 |
| Oral/Pharyngeal | 10,088 |   15 |

***2002 US Cancer Statistics, CDC/NCI, 2005**
**+Parkin M.  International Papillomavirus Conference, Vancouver, Canada,**** ****2005/Trotter H, Franco E, Vaccine; 2006 in press**

## Summary

**Cervix Ca is the 11****th**** most common cancer in U.S. women; occurs mainly among rarely or never screened **
**9,710 new cancer cases and 3,700 cancer deaths estimated in 2006**
**There are racial and socioeconomic disparities in cervical cancer incidence and mortality rates**
**Cervical cancer screening has resulted in a 75% decrease in cervical cancer incidence in the U.S.**

## Summary II

- Survival is high among women detected with early stage disease
- Cost of screening and managing results of abnormal Pap tests is in excess of $4 billion per year
- Other cancers also attributed to HPV; variation by site

## Acknowledgement

**Mona Saraiya, MD**
**Lauri Markowitz, MD**
**Eileen Dunne, MD**
**Beth Unger, MD, PhD**
**HPV Vaccine Workgroup**