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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA062801-01A1
Application #
2104261
Study Section
AIDS and Related Research Study Section 2 (ARRB)
Project Start
1994-06-17
Project End
1999-03-31
Budget Start
1994-06-17
Budget End
1995-03-31
Support Year
1
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Whitham, Hilary K; Hawes, Stephen E; Chu, Haitao et al. (2017) A Comparison of the Natural History of HPV Infection and Cervical Abnormalities among HIV-Positive and HIV-Negative Women in Senegal, Africa. Cancer Epidemiol Biomarkers Prev 26:886-894
Raugi, Dana N; Gottlieb, Geoffrey S; Sow, Papa S et al. (2013) HIV-1 outcompetes HIV-2 in dually infected Senegalese individuals with low CD4ýýý cell counts. AIDS 27:2441-50
Heitzinger, K; Sow, P S; Dia Badiane, N M et al. (2012) Trends of HIV-1, HIV-2 and dual infection in women attending outpatient clinics in Senegal, 1990-2009. Int J STD AIDS 23:710-6
Pavlinac, Patricia B; Hawes, Stephen E; Gottlieb, Geoffrey S et al. (2012) HIV shedding in the oral cavity: an assessment of HIV type, immunovirologic, demographic and oral factors. Sex Transm Infect 88:45-50
Hawes, Stephen E; Sow, Papa Salif; Stern, Joshua E et al. (2008) Lower levels of HIV-2 than HIV-1 in the female genital tract: correlates and longitudinal assessment of viral shedding. AIDS 22:2517-25
Mair, C; Hawes, S E; Agne, H D et al. (2008) Factors associated with CD4 lymphocyte counts in HIV-negative Senegalese individuals. Clin Exp Immunol 151:432-40
Rowhani-Rahbar, Ali; Hawes, Stephen E; Sow, Papa Salif et al. (2007) The impact of HIV status and type on the clearance of human papillomavirus infection among Senegalese women. J Infect Dis 196:887-94
Hawes, Stephen E; Critchlow, Cathy W; Sow, Papa Salif et al. (2006) Incident high-grade squamous intraepithelial lesions in Senegalese women with and without human immunodeficiency virus type 1 (HIV-1) and HIV-2. J Natl Cancer Inst 98:100-9
Hawes, Stephen E; Critchlow, Cathy W; Faye Niang, Mame A et al. (2003) Increased risk of high-grade cervical squamous intraepithelial lesions and invasive cervical cancer among African women with human immunodeficiency virus type 1 and 2 infections. J Infect Dis 188:555-63
Xi, Long Fu; Toure, Papa; Critchlow, Cathy W et al. (2003) Prevalence of specific types of human papillomavirus and cervical squamous intraepithelial lesions in consecutive, previously unscreened, West-African women over 35 years of age. Int J Cancer 103:803-9

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