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Epidemiologic Notes and Reports Risk for Cervical Disease in HIV-Infected Women -- New York City
Recent reports have suggested an association between human immunodeficiency virus (HIV) infection and cervical disease in women (1-5). This report summarizes findings from four studies in New York City that assessed the risk for cervical disease in women infected with HIV (6-10).
Among patients receiving care from two ambulatory-care clinics for HIV-infected women, the prevalence of cervical dysplasia on Papanicolaou (Pap) smear for HIV-positive women was eight and 11 times greater than the prevalence of dysplasia for women residing in the respective communities (6). Specifically, among clinic patients, the proportions of HIV-positive women with dysplasia were 32% (10/31) and 33% (6/18); in contrast, among women in the communities, the prevalences of cervical dysplasia were 4% and 3%, respectively.
The association of HIV infection with cervical squamous intraepithelial lesions (SIL)* and human papillomavirus (HPV) infection of the cervix was prospectively investigated in 132 women attending a methadone maintenance clinic (7,8). Evidence for HPV infection was detected in 67% of symptomatic HIV-positive women, 31% of asymptomatic HIV-positive women, and 27% of HIV-negative women. HPV was more strongly associated with SIL in symptomatic (odds ratio (OR)=29.3; 95% confidence interval (CI)=1.6-551.9) and asymptomatic (OR=8.8; 95% CI=1.6-47.8) HIV-positive women than in HIV-negative women (OR=2.3; 95% CI=0.5-11.7). In women who were not infected with HPV, no association was found between HIV and SIL. The findings of this investigation suggest that HIV-induced immunosuppression may predispose to HPV-mediated cervical cytologic abnormalities.
The characteristics of cervical disease were assessed in women with known HIV status attending a medical center for evaluation of abnormal Pap smears (9). Colposcopic evaluations of 77 patients suggested that cervical intraepithelial neoplasia (CIN) was more severe and extensive in 25 HIV-positive women than in 52 HIV-negative women. Among the HIV-positive women, CIN was a higher grade and more likely to involve multifocal or extensive cervical lesions, multiple sites of the lower genital tract, and the perianal area. The investigators also reported that in a group of 37 patients who were less than 50 years of age and who had invasive cervical carcinoma, seven (19%) were HIV-positive. The seven HIV-positive patients had more advanced stages of disease and poorer outcomes following therapy than the 30 HIV-negative patients. These findings suggest that HIV infection may influence the rate of progression of both preinvasive and invasive cervical neoplasia.
Finally, among 32 HIV-infected women who were evaluated for cervical disease by Pap smear and colposcopically directed biopsies (10), three (9.4%) had abnormal cytology on Pap smear; however, for 27 (84.4%), histology was abnormal on biopsy, including 13 (40.6%) with CIN and 14 (43.8%) with chronic cervicitis. The findings of this study suggest that, in HIV-positive women, Pap smear and cervical biopsy results may correlate poorly. Reported by: M Maiman, MD, R Fruchter, PhD, State Univ of New York Health Science Center, Brooklyn; R Klein, MD, Montefiore Medical Center/Albert Einstein Coll of Medicine; C Marte, MD, Community Health Project, Bellevue Hospital; S Schultz, MD, MA Chiasson, DrPH, New York City Dept of Health. Div of HIV/AIDS, Center for Infectious Diseases; Div of STD/HIV Prevention, Center for Prevention Svcs; Div of Chronic Disease Control and Community Intervention, Center for Chronic Disease Prevention and Health Promotion, CDC.
Editorial Note: The findings of the investigations in New York City are consistent with previous reports suggesting an association between HIV infection and cervical disease in women (1-5). However, methodologic concerns about these four studies emphasize the need for additional assessment of an association between HIV infection and cervical disease. For example, the increased prevalence of cervical dysplasia in the HIV-positive women at the two ambulatory-care clinics (6) may have been associated with other possible risk factors. In addition, the community controls used in that study may not be directly comparable to the study group, since the HIV-positive women may have been more likely to have had sexual contact with multiple partners, thereby independently increasing their risk for cervical disease. Other methodologic concerns related to these studies include limited sample sizes, limitations of cytologic screening for diagnostic purposes, and potential selection bias. Finally, the study of HIV-positive women who were evaluated by Pap smear and cervical biopsy was not blinded and lacked a control group (10).
These reports and other investigations have not determined whether HIV-infected women are at increased risk for cervical cancer. This risk may be assessed indirectly by examination of trends of cervical cancer rates in areas with high prevalences of HIV-infected women. For example, in New York City, where the prevalence of HIV infection in childbearing women (12.5 per 1000 in 1987-88) is one of the highest among U.S. cities, the incidence of cervical cancer in women aged 15-44 years did not increase from 1981 through 1986 (12,13). In the United States, approximately 85% of women with AIDS or HIV infection are of reproductive age (15-44 years). However, in 1987, cervical cancer rarely was listed among HIV-related deaths in women of reproductive age (14). Because the number of HIV-infected women has continued to increase since 1987, trends in cervical cancer rates will need to be examined for more recent years.
Clarification of the relationship between HIV infection and cervical cancer and dysplasia is also complicated by complexities related to interpretation of cervical cytologic abnormalities. Squamous cell carcinoma of the cervix and its precursors form a spectrum of disease, ranging from mild dysplasia (CIN 1) to invasive carcinoma. In addition, although dysplasia is the precursor of cervical cancer, not all dysplastic tissue progresses to invasive disease. Without therapy, cervical dysplasia can regress to normal tissue, persist without change, or progress to invasive disease. Whether HIV-induced immune suppression substantially alters the course and severity of cervical dysplasia is unknown, but the findings summarized in this report indicate a need for further investigation.
The etiology of cervical cancer may be multifactorial (15), including factors such as number of sex partners, age at first intercourse, infectious agents (particularly HPV), cigarette smoking, certain dietary deficiencies, and immunosuppression. The number of sex partners, both of women with cervical cancer and their sexual contacts, contributes independently to the risk, suggesting that cervical cancer is a sexually transmitted disease. Thus, the behavior that places women at risk for HIV infection may also increase their risk for cervical carcinoma and of acquiring viral infections that may be associated with cervical carcinoma. Therefore, epidemiologic studies that can adjust for potential confounding variables, such as sexual behavior, are needed to determine whether HIV infection places women at additional risk for cervical disease.
In 1988, a consensus recommendation for cervical cancer screening was adopted by the American Cancer Society, the National Cancer Institute, the American College of Obstetricians and Gynecologists, the American Medical Association, the American Nurses' Association, the American Academy of Family Physicians, and the American Medical Women's Association (16). The recommendation suggests that all women who are or who have been sexually active or who have reached age 18 years should have an annual Pap test and pelvic examination. After a woman has had three or more consecutive satisfactory normal annual examinations, the Pap test may be performed less frequently at the discretion of her physician. Another advisory group, the U.S. Preventive Services Task Force, recommended in 1989 that Pap smears should begin with the onset of sexual activity and should be repeated every 1-3 years at the physician's discretion (17). The time interval between Pap tests recommended by the physician should be based on the presence of risk factors for cervical cancer. In accordance with these recommendations and information suggesting that HIV-infected women may be at increased risk for cervical disease, HIV-infected women should have a Pap smear annually.
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9. Maiman M, Fruchter RG, Serur E, et al. Human immunodeficiency virus infection and cervical neoplasia. Gynecol Oncol 1990;38:377-82. 10. Tarricone NJ, Maiman M, Vieira J. Colposcopic evaluation of HIV seropositive women (Abstract). VI International Conference on AIDS. Vol 2. San Francisco, June 20-24, 1990:378. 11. National Cancer Institute Workshop. The 1988 Bethesda system for reporting cervical/vaginal cytological diagnoses. JAMA 1989;262:931-4. 12. Novick LF, Berns D, Stricof R, Stevens R, Pass K, Wethers J. HIV seroprevalence in newborns in New York state. JAMA 1989;261:1745-50. 13. New York State Department of Health. Time trends in cancer incidence: 1977-1986. Albany, New York: New York State Cancer Registry, 1990. 14. Chu SY, Buehler JW, Berkelman RL. Impact of the human immunodeficiency virus epidemic on mortality in women of reproductive age, United States. JAMA 1990;264:225-9. 15. Munoz N, Bosch FX. Epidemiology of cervical cancer. In: Munoz N, Bosch FX, Jensen OM, eds. Human papillomavirus and cervical cancer. Lyon, France: International Agency for Research on Cancer (WHO), 1989:9-39. 16. Fink DJ. Change in American Cancer Society checkup guidelines for detection of cervical cancer. CA 1988;38:127-8. 17. US Department of Health and Human Services, Preventive Services Task Force. Screening for cervical cancer. In: Guide to clinical preventive services: an assessment of the effectiveness of 169 interventions. Baltimore: Williams and Wilkins, 1989:57-62.
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