Women with HIV/AIDS are at high risk for cervical cancer. Through the use of highly active antiretroviral therapy (HAART), an increasing number of HIV+ women with varied immune status are now entering the age groups in which cervical cancer rates reach their peak. Understanding the biologic risk factors for cervical disease and human papillomavirus (HPV), the viral cause of cervical cancer, in middle-aged HIV+ women is a priority. This application seeks support to continue our studies of cervical HPV/dysplasia in a large, long term HIV+ cohort. The planned studies will address several important issues regarding aging and immune function that are likely to have a major impact on the control of HPV/dysplasia in HIV+ women: (i) the effects of menopause and accelerated immune aging (caused by HIV) on the type-specific natural history of HPV and cervical dysplasia; (ii) the local cervical immune infiltrates that distinguish cervical intraepithelial neoplasia (CIN)-1 that regress vs progress to CIN-2+ and, secondly, those CIN that are treated but recur within 1 year; and lastly (iii) the polymorphisms in KIR and IL28B genes (which are involved in natural killer (NK) cell activation) that affect the NK cell - HPV/dysplasia relationship.

Women with HIV/AIDS are at high risk for cervical cancer, and have high rates of infection with human papillomavirus (HPV), the viral cause of cervical cancer. Through semiannual evaluations of 2,793 HIV+ and 975 HIV- women enrolled in the Women's Interagency HIV Study (WIHS), a multicenter cohort, the "WIHS HPV Study" is intended to be the authoritative investigation of the effects of HIV coinfection on HPV and cervical dysplasia. A major demographic change that must be addressed is the aging of the HIV+ population. Many are now middle-aged. In particular, a large number of HIV+ women have undergone menopause. Menopause has been associated with diminished immune response, as well as cervicovaginal atrophy (weakening the epithelial barrier). A recent study reported high HPV prevalence in peri-/post- vs pre-menopausal HIV- women. Amongst HIV+ women, however, the impact of menopause on HPV natural history / dysplasia is unknown. Furthermore, beyond total CD4+ T-cell count, the nature of the immune deficits in HIV+ women which effect HPV are poorly understood.