It is estimated that 15% of all human cancers are associated with viruses. A much higher incidence of virus-associated malignancies occurs in immunocompromised patients, as during AIDS, post-transplantation, and some congenital immunodeficiency diseases. Infectious viral agents may transform cells directly or induce chronic inflammation, an important cofactor for malignant transformation. Therefore, we hypothesize that AIDS-related malignancies are caused in part by reactivated or de novo viral infections due to a decrease in immune surveillance in this population. As a pilot study, we will follow a cohort of HIV infected individuals who report engaging in anal receptive sex, which puts them at high risk for anal human papillomavirus (HPV) infection and therefore anal cancer. For this study, anal swabs will be collected for DNA and RNA isolation. Clinical data will also be collected such as pertinent medical and social history, anal Pap smear cytology, CD4 counts, and HIV viral loads. We plan to develop a comprehensive Human virus-specific microarray (HVchip) that includes all known HPV subtypes (>100) for HPV typing and also possibly new type identification. Microarray analysis of nucleic acids from the cohort samples will be correlated to the collected clinical data and disease related outcomes. Subsequently, we may initiate multicenter or international collaborations to identify other potential HPV associated AIDS-related malignancies, such as squamous cell carcinoma of the conjuntiva in Africa. In addition, one of our long-term goals is to create a comprehensive pathogen specific microarray for etiological or surrogate pathogen discovery in other AIDS-related diseases. ? ?
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