Cancer of the Cervix An Overview

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					    Cancer of the Cervix
           An Overview


  Herschel W. Lawson, M.D.
        June, 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
             The Most Common Cancers in Women

                    More developed               Less developed
                      countries                     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                                                               128.9
       Lung & Bronchus                                   52.5
         Colon & Rectum                               47.0
  Corpus & Uterus, NOS                    23.5
                   Ovary              15.8
 Non-Hodgkin Lymphoma                 15.4
   Melanomas of the Skin            12.4
                 Thyroid           10.7
         Urinary Bladder          9.8
                Pancreas          9.5
             Cervix Uteri         9.2
               Leukemias          8.7
   Kidney & Renal Pelvis         8.4
   Oral Cavity & Pharynx        6.0
            Brain & CNS         5.5

                            0        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

                                10
 Mortality Rate (per 100,000)




                                8

                                6

                                4

                                2

                                0
                                46
                                     48
                                          50
                                               52
                                                    54
                                                         56
                                                              58
                                                                   60
                                                                        62
                                                                             64
                                                                                  66
                                                                                       68
                                                                                            70
                                                                                                 72
                                                                                                      74
                                                                                                           76
                                                                                                                78
                                                                                                                     80
                                                                                                                          82
                                                                                                                               84
                                                                                  Year


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
                                35

                                30

                                25
R a te (p e r 1 0 0 , 0 0 0 )




                                20

                                15                                                                                        Incidence Black


                                10                                                                                        Incidence White
                                        Death Black


                                5
                                        Death White
                                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
                                                                                                          Year

                                     *Rates are per 100,000 and are age-adjusted to the 2000 U.S. standard population.
                                     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

                              12
                                                                                                       Incidence
 R a te p e r 1 0 0 , 0 0 0




                              10                                                                          Death


                              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   85+
                                                                   Age Group


 *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

                                                             0.90-2.53

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

                                                                      5%-10%



            50%-60%                                  False negative
                                                     cytology test
                                                                                     10%-15%

                                   Never or              Cytology test abnormal,
                                   Rarely                patient lost to follow-up


                                   Screened                  Cytology test abnormal,
                                                             mismanaged
                                                                                       10%-15%

                                                         Rapidly
                                                         progressive
                                              Uncommon
                                              cancers
                                              difficult to                5%-10%
                                              detect
Sources:NIH Consensus Conference
Janerich, Connecticut
Sung, California
                                                      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)
HSIL
Squamous Cell Cancer
                         Glandular Cell
Atypical glandular cells (AGC)
Adenocarcinoma in situ (AIS)
Adenocarcinoma
 Cervical Cancer Screening Recommendations

                    USPSTF                   ACS                ACOG
                     2003                    2002                2003
Age to           Age 21 or within      Age 21 or within      Age 21 or within
start             3 yrs of sexual       3 yrs of sexual       3 yrs of sexual
                     activity              activity              activity

Interval
   <30 yr                                  Conv: 1 yr          1 yr
                   Conv: at least          LBC: 2 yr
                    every 3 yrs
                                           2-3 yrs             2-3 yrs
   ≥ 30 yr


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                                                                    % Pap test
                                                                                past 3 years
       All women                                                                      82%
       Insured
          yes                                                                         85%
          no                                                                          62%
       Country of birth
         US born                                                                      83%
         Foreign born in U.S. <10 yrs                                                 61%


       Race/Ethnicity
         Hispanic                                                                     77%
         Non-Hispanic White                                                           83%
         Non – Hispanic Black                                                         84%
         Asian                                                                        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              ACS                   ACOG          ASCCP
ASC-US triage      Insufficient        Not addressed         Recommended   Recommended
                   Evidence


Primary            Not addressed       Option                Recommended   Recommended
screening with
Pap test

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 Hildesheim, A., National Cancer Institute
Evaluation of an Abnormal Pap Test


Repeat cytology
HPV DNA test
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%
                                                                                 Abnormal cervical
                                                                                 cytology and
                                                                                 treatment of
                                                                                 neoplasia
                                            90%
                                                                                 Cervical cancer




                                                                                 Anogenital warts




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

Cervix Ca is the 11th 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.
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
Acknowledgement

Mona Saraiya, MD
Lauri Markowitz, MD
Eileen Dunne, MD
Beth Unger, MD, PhD