Cancer of the Cervix and Other HPV-related Cancers An Overview by Biscuit350

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									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

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

The Most Common Cancers in Women
More developed countries

Less developed countries
Breast Cervix Ovary Endometrium
Colon/rectum

Lung Stomach
600 400 200 0

200

400

600

Annual number of cases (thousands)
Adapted from Parkin et al, Eur J Cancer 37:S4, 2001

Cervical Cancer Surveillance
National Program of Cancer Registries (NPCR) and Surveillance Epidemiology and End Results (SEER)

  

SEER since 1973 NPCR Since 1995 96% population coverage

SEER NPCR NPCR/SEER SEER Metro

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)
+Cancer

Facts and Figures, 2006; American Cancer Society

Age-Adjusted Invasive Cancer Incidence Rates, Among Women, U. S., 2000
Breast Lung & Bronchus Colon & Rectum Corpus & Uterus, NOS Ovary Non-Hodgkin Lymphoma Melanomas of the Skin Thyroid Urinary Bladder Pancreas Cervix Uteri Leukemias Kidney & Renal Pelvis Oral Cavity & Pharynx Brain & CNS 0 128.9 52.5 47.0 23.5 15.8 15.4 12.4 10.7 9.8 9.5 9.2 8.7 8.4 6.0 5.5 20 40 60 80 100 120 140

Rate per 100,000

United States Cancer Statistics: 2000 Incidence; NPCR

Cervical Cancer Mortality Rates, U.S., 1946-1984
12

Mortality Rate (per 100,000)

10 8 6 4 2 0

46

48

50

52

54

56

58

60

62

64

66

68

70

72

74

76

78

80

82

Year

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

84

Invasive Cervical Cancer Incidence and Mortality Rates,* by Race, SEER in US, 1975-2002
35 30
Rate (per 100,000)

25 20
Incidence Black

15
Death Black Incidence White

10 5 0 '75 '76 '77 '78 '79 '80 '81 '82 '83 '84 '85 '86 '87 '88 '89 '90 '91 '92 '93 '94 '95 '96 '97 '98 '99 '00 '01 '02
*Rates are per 100,000 and are age-adjusted to the 2000 U.S. standard population.

Death White

Year

Source: SEER Cancer Statistics Review, 1975-2002

Invasive Cervical Cancer Incidence and Mortality Rates,* by Age Group, SEER in U.S., 1998-2002
16 14
Incidence

12
Rate per 100,000

Death

10 8 6 4 2 0 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 Age Group

85+

*Source: SEER Cancer Statistics Review, 1975-2002

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

3.93-6.76

3.21-3.93
2.53-3.21

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

0.90-2.53

Sparse

Factors Contributing to Cervical Cancer
5%-10%

50%-60%

False negative cytology test

10%-15%

Never or Rarely Screened

Cytology test abnormal, patient lost to follow-up

Cytology test abnormal, mismanaged

10%-15%

Sources:NIH Consensus Conference Janerich, Connecticut Sung, California

Uncommon cancers difficult to detect

5%-10%

9%-12%

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
Age to start Interval
<30 yr
Conv: at least every 3 yrs

ACS 2002
Age 21 or within 3 yrs of sexual activity

ACOG 2003
Age 21 or within 3 yrs of sexual activity

Age 21 or within 3 yrs of sexual activity

Conv: 1 yr LBC: 2 yr
2-3 yrs

1 yr

≥ 30 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

Prevalence of Cervical Cancer Screening, National Health Interview Survey, United States, 2000
Group
All women Insured Yes No Country of birth US born Foreign born in U.S. <10 yrs Race/Ethnicity Hispanic Non-Hispanic White Non – Hispanic Black Asian

% Pap test past 3 years
82%

85% 62% 83% 61%

77% 83% 84% 71%

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.

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
ASC-US triage Insufficient Evidence

ACS

ACOG

ASCCP

Not Recommended Recommended addressed

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. CA
15,000

HSIL 300,000 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

Estimated Annual Direct Medical Cost of Specific Sexually Transmitted Infections, U.S., 2000
$7.0 $6.0 $5.0

($ billions)

$4.0 $3.0 $2.0 $1.0 $0.0 HIV HPV HSV-2 Chlamydia Others

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.

Components of Total Cost Burden of HPV, U.S., 2000
4% 6%

90%

Abnormal cervical cytology and treatment of neoplasia Cervical cancer

Anogenital warts

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

Cancers Attributable to Infection with Oncogenic HPV Types, U.S., 2002
Site Total Cancers*
% Estimated HPV Attributable Fraction+

Cervix Anus
Vulva/Vagina Penis

12,085 3,703
4,480 985

100 85
40 40

Oral/Pharyngeal
*2002 US Cancer Statistics, CDC/NCI, 2005

10,088

15

+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


								
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