Human papillomavirus (HPV) infection is though to play a central role in the development of cancers and those precancerous lesions of the cervix (cervical intraepithelial neoplasia grade 2-3[CIN2-3] most likely to develop into invasive cancer. More recently, cross sectional studies have shown HIV infection to be associated with an increased risk of such HPV-related lesions. Invasive cervical cancer is now considered an AIDs defining illness among HIV infected women. However, cohort studies are needed to define the absolute risk of CIN2-3 in women with HIV infection, to characterize the role of specific types of HPV and the role of potential cofactors in development of CIN2-3 in HIV infected women, and to compare efficacy of ablative therapy for CIN2-3 among women with and without HIV. Our cross sectional study in Senegal, now beginning its fourth and last clinical year, is the only study currently examining both HIV-1 and HIV-2 with respect to the prevalence of HPV and CIN. We have established an infrastructure that will facilitate longitudinal studies of the development and recurrence, after treatment, of CIN2-3. Thus, we propose to extend the findings of our cross-sectional study by conducting a cohort study of women with and without HIV-1 and HIV-2 at our present study sites. Senegal is the ideal site for the proposed study since HIV- 1 and HIV-2 are equally prevalent, but dual HIV-1/2 infection is uncommon. We propose to 1) compare the risk of development of biopsy proven CIN2-3 in relationship to HIV-1 and/or HIV-2 among HPV positive women; 2) to characterize the risk of development of CIN2-3 among HIV infected women with respect to the role of HPV, specific types of HPV, and among HPV positive women, with respect to infection with other STDs; 3) to assess the influence of HIV-1 and/or HIV-2 on the natural history of cervical HPV; and 4) to compare the outcome of ablative treatment of CIN2-3 among women with and without HIV with respect to the risk of recurrence of CIN1 and CIN2-3. We will enroll and follow 900 cytologically negative women including 300 women with HIV-1, 300 with HIV-2, and 300 HIV seronegative /HPV positive women. In addition, 327 women with and without HIV who have been treated by conization for CIN2-3 will be enrolled. Women will be examined every four months for 3 years by colposcopy, cytology, and tested for HPV, other STDs and CD4 levels. Knowledge from the proposed study will aid in the development of strategies for cervical cancer prevention among HIV infected women.
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