Opportunistic infections of the oral cavity afflict 50% of all HIV infected patients, and include oropharyngeal candidiasis (OPC), oral hairy leukoplakia (OHL) and oral warts caused by the mucosatropic human papillomavirus (HPV). The aggressive treatment of HIV with highly-active antiretroviral therapy (HAART) has significantly improved the HIV patient's health and prognosis by lowering systemic HIV viral loads and restoring immune function primarily through increases in CD4+ T lymphocytes. This has resulted in a substantial decrease in the incidence of HIV-associated opportunistic oral diseases, including OPC and (OHL). In stark contrast, the incidence of oral papillomas (warts) has reportedly increased since the widespread administration of HAART. Preliminary analysis has identified HPV-32 as the predominant genotype found in oral warts in the New Orleans HIV+ cohort. It is felt that asymptomatic oral HPV infection occurs frequently but oral warts occur infrequently, presumably due to immunological control of the virus. The critical aspects of the immune response that prevent the progression from asymptomatic HPV infection to HPV disease are unknown, but previous studies have focused on HPV genotype-specific response against the major capsid protein, LI. The increased rate of HPV-related oral pathology seen in HIV+ patient's highlights the need for a more thorough understanding of the immune response to oral HPV infections. Furthermore, the accessibility of the oral cavity affords a unique opportunity to conduct rigorous analysis of HPV infection, immunity and pathogenesis. To initiate these studies, the development of the immunological assays specific for oral HPV genotypes such as HPV-32 are required. We hypothesize that HPV-32 specific humoral and cellular immunoassays can be developed and utilized to screen populations for HPV-32 specific immune responses. We propose to develop an enzyme-linked immunosorbent assay (ELISA) for detection of HPV-32-specific antibodies in serum, and lymphoproliferative and flowcytometric assays for the detection of HPV-32-specific T cell responses. These assays will be tested for optimal assay conditions, specificity, and reproducibility. Ultimately these assays will be used to investigate the role of immunity in the acquisition and subsequent clearing or progression of oral HPV infections, particularly in the highly susceptible HIV+ patient. The goal of this project is to develop the tools necessary to gain a better understanding of the humoral and cellular immune response to oral HPV infection, particularly in the HIV+ individual. The understanding of immune response to oral HPV infection may help to predict HPV disease progression as well as elucidate therapeutic and preventive strategies for HPV-related disease.
