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Cervical Cancer
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Screening for Cervical Cancer

Summary of Evidence

Evidence strongly suggests a decrease in mortality from regular screening with Pap tests in women who are sexually active or who have reached 18 years of age. The upper age limit at which such screening ceases to be effective is unknown.

Levels of Evidence: 3,4,5

Evidence obtained from cohort or case-control analytic studies, preferably from more than one center or research group.

Evidence obtained from multiple time series with or without intervention.

Opinions of respected authorities based upon clinical experience, descriptive studies, or reports of expert committees.

Significance

In 1996, an estimated 15,700 cases of invasive cervical cancer are expected to occur, with about 4,900 women dying from this disease.[1] From 1950 to 1970, the incidence and mortality rates of invasive cervical cancer fell impressively by more than 70%.[2] Since the early 1980s, however, the rates of incidence and mortality appear to be decreasing more slowly. According to incidence and mortality rates, screening for cervical cancer should start in the late teens when these rates begin their upward trend. Rates for carcinoma in situ reach a peak for both black and white women between 20 and 30 years of age.

After the age of 25, however, the incidence of invasive cancer in black women increases rapidly with age, while in white women the incidence rises more slowly. Mortality also increases with advancing age, with dramatic differences between black and white women.

Extra effort is warranted to reach older women who have not been screened. Over 25% of the total number of invasive cervical cancers occur in women older than 65, and 40%-50% of all women who die from cervical cancer are over 65 years of age.[3,4] A large proportion of women, particularly elderly black women and middle-aged poor women, have not had regular Pap smears.[5] In some areas, as many as 75% of women over 65 have not had a Pap smear within the previous 5 years.[6] These patterns underscore the importance of special screening efforts targeted to reach women who do not receive regular screening.

References

1. Parker SL, Tong T, Bolden S, et al.: Cancer statistics, 1996. Ca-A Cancer Journal for Clinicians 46(1): 5-27, 1996.
2. National Cancer Institute: Cancer Statistics Review 1973-1987. Bethesda, NCI Publication No. (NIH)90-2789, 1990.
3. Surveillance Program, Division of Cancer Prevention and Control, National Cancer Institute. Unpublished data, 1990
4. Remington P, Lantz P, Phillips JL: Cervical cancer deaths among older women: implications for prevention. Wisconsin Medical Journal 89(1): 30, 32-34, 1990.
5. Makuc DM, Freid VM, Kleinman JC: National trends in the use of preventive health care by women. American Journal of Public Health 79(1): 21-26, 1989.
6. Mandelblatt J, Gopaul I, Wistreich M: Gynecological care of elderly women: another look at Papanicolaou smear testing. Journal of the American Medical Association 256(3): 367-371, 1986.

Evidence of Benefit

The widespread acceptance of the Pap smear makes the possibility of testing the efficacy of cervical cytology by randomized trials remote. There is, nevertheless, substantial evidence from observational studies that mortality from cervical cancer can be reduced by screening.

Mortality from cervical cancer has decreased in several large populations following the introduction of well-run screening programs.[1-4] Data from several large Scandinavian studies show sharp reductions in incidence and mortality following the initiation of organized screening programs. Iceland reduced mortality rates by 80% over 20 years, and Finland and Sweden reduced their mortality by 50% and 34%, respectively.[1] Similar reductions have been found in large populations in the US and Canada.

Reductions in incidence and mortality seem to be proportional to the intensity of screening efforts. The Scandinavian countries with the highest rates of screening activity reported greater reductions in mortality than those countries with lower rates of screening.[1,5] Mortality in the Canadian provinces was reduced most remarkably in British Columbia, which had screening rates two to five times those of the other provinces.[6]

Case-control studies have found that the risk of developing invasive cervical cancer is 3-10 times greater in women who have not been screened.[7-10] Risk also increases with longer duration following the last normal Pap smear, or similarly, with decreasing frequency of screening.[11,12] Screening every 2-3 years, however, has not been found to increase significantly the risk of finding invasive cervical cancer above the risk expected with annual screening.[12,13]

The analysis of survival data shows that survival appears to be directly related to the stage of disease at diagnosis. The 5-year relative survival rate for cervical cancer is 88% for women with an initial diagnosis of localized disease. For those initially diagnosed with distant disease, the survival rate is only 13%. Early detection, using cervical cytology, is currently the only practical means of detecting cervical cancer in localized or premalignant stages.

Targeting high-risk patients:

Progress in mortality reduction will be accelerated most significantly by increasing the percentage of cervical neoplasms discovered in the precancerous or localized stages. This can be accomplished most effectively by screening women at greatest risk for cervical cancer, i.e., those who have not had a Pap test or those who have not had one for several years. Often, these women are older, of lower socioeconomic status, and may be members of minority groups, and are often seen by physicians for a variety of acute and chronic conditions unrelated to preventive medical care.[13-17] Other well-known risk factors, such as early age of first intercourse and multiple sexual partners, have less practical clinical significance due to the difficulty in obtaining adequate histories of these risk factors. Advances in understanding the relationship between specific HPV types and the risk of cervical neoplasia may have future applications in targeting high-risk groups for screening and other preventive interventions. In particular, HPV testing is under investigation as an intermediate test in the evaluation of women with minor cytologic abnormalities. In the majority of such cases, abnormal changes regress spontaneously; however, some women may harbor an occult high-grade lesion that should be treated. In one study of women with equivocal Pap smear results, testing for elevated levels of HPV DNA from cancer-associated viral types was found to be more sensitive than repeat cytology alone in identifying women with high-grade lesions who required therapy.[18] In another study, of the 31 women who tested negative for HPV16 by DNA-based methods, 29 (94%) were also negative for systemic IgG antivirion antibodies by an enzyme-linked immunosorbent assay (ELISA). [19,20] However, of the 54 women positive for HPV16 by DNA-based methods, only 32 (59%) were also found positive by the ELISA method.

References

1. Laara E, Day NE, Hakama M: Trends in mortality from cervical cancer in the Nordic countries: association with organised screening programmes. Lancet 1(8544): 1247-1249, 1987.
2. Christopherson WM, Lundin FE, Mendez WM, et al.: Cervical cancer control: a study of morbidity and mortality trends over a twenty-one year period. Cancer 38(3): 1357-1366, 1976.
3. Miller AB, Lindsay J, Hill GB: Mortality from cancer of the uterus in Canada and its relationship to screening for cancer of the cervix. International Journal of Cancer 17(5): 602-612, 1976.
4. Johannesson G, Geirsson G, Day N: The effect of mass screening in Iceland, 1965-1974, on the incidence and mortality of cervical carcinoma. International Journal of Cancer 21(4): 418-425, 1978.
5. Sigurdsson K: Effect of organized screening on the risk of cervical cancer: evaluation of screening activity in Iceland, 1964-1991. International Journal of Cancer 54(4): 563-570, 1993.
6. Benedet JL, Anderson MB, Matisic JP: A comprehensive program for cervical cancer detection and management. American Journal of Obstetrics and Gynecology 166(4): 1254-1259, 1992.
7. Aristizabal N, Cuello C, Correa P: The impact of vaginal cytology on cervical cancer risks in Cali, Colombia. International Journal of Cancer 34(1): 5-9, 1984.
8. Clarke EA, Anderson TW.: Does screening by "Pap" smears help prevent cervical cancer?: a case-control study. Lancet 2(8132): 1-4, 1979.
9. La Vecchia CL, Franceschi S, Decarli A, et al.: "Pap" smear and the risk of cervical neoplasia: quantitative estimate from a case control study. Lancet 2(8406): 779-782, 1984.
10. Herrero R, Brinton LA, Reeves WC, et al.: Screening for cervical cancer in Latin America: a case-control study. International Journal of Epidemiology 21(6): 1050-1056, 1992.
11. Celentano DD, Klassen AC, Weisman CS, et al.: Duration of relative protection of screening for cervical cancer. Preventive Medicine 18(4): 411-422, 1989.
12. International Agency for Research on Cancer Working Group on Evaluation of Cervical Cancer Screening Programmes: Screening for squamous cervical cancer: duration of low risk after negative results of cervical cytology and its implication for screening policies. British Medical Journal 293(6548): 659-664, 1986.
13. Kleinman JC, Kopstein A: Who is being screened for cervical cancer? American Journal of Public Health 71(1): 73-76, 1981.
14. Surveillance Program, Division of Cancer Prevention and Control, National Cancer Institute. Unpublished data, 1990
15. Remington P, Lantz P, Phillips JL: Cervical cancer deaths among older women: implications for prevention. Wisconsin Medical Journal 89(1): 30, 32-34, 1990.
16. Makuc DM, Freid VM, Kleinman JC: National trends in the use of preventive health care by women. American Journal of Public Health 79(1): 21-26, 1989.
17. Mandelblatt J, Gopaul I, Wistreich M: Gynecological care of elderly women: another look at Papanicolaou smear testing. Journal of the American Medical Association 256(3): 367-371, 1986.
18. Cox JT, Lorincz AT, Schiffman MH, et al.: Human papillomavirus testing by hybrid capture appears to be useful in triaging women with a cytologic diagnosis of atypical squamous cells of undetermined significance. American Journal of Obstetrics and Gynecology 172(3): 946-954, 1995.
19. Kirnbauer R, Hubbert NL, Wheeler CM, et al.: A virus-like particle enzyme-linked immunosorbent assay detects serum antibodies in a majority of women infected with human papillomavirus type 16. Journal of the National Cancer Institute 86(7): 494-499, 1994.
20. Galloway DA: Papillomavirus capsids: a new approach to identify serological markers of HPV infection. Journal of the National Cancer Institute 86(7): 474-475, 1994.

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