Women with HIV/AIDS are at high risk of cervical cancer, and have high rates of infection with human papillomavirus (HPV), the viral cause of cervical cancer. Through the semiannual evaluation of 2,793 HIV+and 975 HIV- women enrolled in the Women's Interagency HIV Study (WIHS), a multicenter cohort, the """"""""WIHS HPV Investigation"""""""" is intended to be the definitive study of the effects of HIV coinfection on HPV and cervical dysplasia. This application seeks support for continuation of HPV research in the WIHS. The proposed project will be the first systematic effort to study type-specific differences in the effects of host immune status on HPV natural history in HIV+ women. Our recent results showed that HPV 16, the type that accounts for half of all cervical cancers, was the least affected by immune status (CD4+ count) of any HPV type. Two HPV types related to HPV 16 were also weakly associated with CD4+. Other HPVs, however, have not been adequately characterized, nor could we previously address the strong interaction between the effects of plasma HIV RNA and CD4+ count. Continuation of the WIHS HPV Investigation will provide the needed statistical power to examine HPV type-specific results by combined plasma HIV RNA/CD4+ strata, and it will generate the only truly long term prospective data regarding HPV infection in HIV+ women -valuable data in an era in which women can live for years with HIV. This application also represents an important opportunity to study local cervical HIV levels and their effects on HPV infection. It is known that there is substantial compartmentalization of HIV in the genital tract, but whether cervical HIV RNA levels are independently or, compared with plasma levels, more strongly associated with HPV has not been determined. Finally, once infection with an oncogenic HPV is established it remains unclear what role immune status plays in progression to severe cervical dysplasia. Continued follow-up in the WIHS will, for the first time, make it possible to prospectively study the risk factors for severe cervical dysplasia (a true cancer precursor) in HIV+ women. In summary, the aims are to study: (i) type-specific differences in the effects of host immune status on HPV natural history; (ii) the relationship between cervical HIV RNA levels and HPV infection; (iii) risk factors for progression to severe cervical dysplasia in HIV+ women.
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