Project 1-Preventing cervical cancer in HIV-infected women

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Abstract In contrast to other HIV-associated cancers, the incidence of cervical cancer has not declined in the era of antiretroviral therapy (ART), and is the most common cancer among Kenyan and Ugandan women. These countries each have high HIV prevalence, which greatly accelerates the progression of cervical cancer, even in women receiving ART and achieving “reconstituted” immune systems. Better methods of screening are needed, and we need to understand cofactors related to HPV infection, the virus that causes cervical cancer. The long-term objective of our project is to help eradicate cervical cancer in HIV-infected Kenyan and Ugandan women. We will test our approach in a study of HIV-infected women. First, we will evaluate HR-HPV DNA testing of self-collected vaginal swabs combined with VIA in detecting biopsy-proven cervical intraepithelial neoplasia grades 2, 3, or worse (CIN 2/3+) in HIV-infected women living in Kenya or Uganda. We hypothesized that detection of biopsy-proven CIN 2/3+ is higher among HIV-infected women with both HR- HPV DNA positivity and VIA abnormality compared to those with only one or neither of these tests positive. Second, we will determine if aflatoxin, a carcinogenic and immunosuppressive compound found in contaminated corn, is a risk factor for oncogenic HPV detection and cervical cancer among HIV-infected Kenyan and Ugandan women. We hypothesize that regardless of HIV-status, aflatoxin is a risk factor for HR- HPV detection, HR-HPV persistence, and biopsy-proven CIN 2/3+, that the impact of aflatoxin on HR-HPV detection, HR-HPV persistence, and biopsy-proven CIN 2/3+ will be significantly greater in HIV-infected women than in HIV-uninfected women, and that the immunosuppressive effects of aflatoxin impair the host’s ability to control HIV in spite of ART use. Accomplishment of our aims will help improve care for all women in Kenya and Uganda, and help in the battle against cervical cancer in HIV-infected women.