The incidence of human papillomavirus (HPV)-associated oral and anogenital cancer in human immunodeficiency virus (HIV)-positive individuals is substantially higher than in HIV-negative individuals. HIV may increase the risk of HPV-related disease by reducing of immune response to HPV or other direct molecular interactions between the two viruses. Our preliminary data indicate that the HIV proteins tat and gp120 disrupt intercellular junctions of mucosal epithelium and facilitate HPV entry into epithelium. HPV entry into HIV-disrupted epithelium can be inhibited by inactivation of junctional proteins occludin and claudin 1, suggesting that these proteins may serve as receptors for HPV infection. These findings suggest that HIV- induced disruption of mucosal epithelium may facilitate HPV infection by dissociating epithelial junctions and exposing HPV receptors. Our specific aims are: 1) To study the role of HIV tat and gp120-mediated exposure to the tight junction proteins occludin and claudin 1 in HPV binding. 2) To study the role of occludin and claudin 1 in HPV entry into epithelial cells with HIV tat and gp120-disrupted epithelial junctions. Investigation of the role of HIV in potentiating HPV infection through mucosal disruption is important to understand the basic biology of HPV infection of the mucosal epithelium in HIV-positive individuals.  This knowledge may also lead to development of new drugs that inhibit mucosal disruption and therefore prevent HPV infection.