The long term aim of this study is to understand better the immune responses to primary or initial human papillomavirus (HPV) infection of the cervix in association with persistence or clearance of HPV infection. Persistence of HPV infections in the cervix appears to be essential for the development of high grade squamous intra-epithelial lesions and invasive cancers. It is plausible that persistence is a result of an immunologic failure. Understanding initial responses to HPV may be critical to vaccine or therapeutic developments as well provide insight in understanding immune responses to subsequent incident infections of the cervix. in order to study initial responses, it is critical to have access to a population of recent sexually active persons. Access to such a group is invaluable because immunologic responses to HPV in """"""""HPV-naive"""""""" cervixes have not been previously characterized. Consequently, the aim of the study is to intensely characterize immune activity to HPV as well as factors that may affect immune activity over time in a small group of recently sexually active adolescents. Using a longitudinal study design among a group of recently sexually active adolescent women, we will examine: 1. changes in the local cervical cytokine milieu, specifically interferon(IFN)-gamma and interleukins (IL)-4, 10, and 12 in association with initial HPV infection as well as persistent infection or clearance. Local cytokine production will be evaluated using reverse transcription (RT) polymerase chain reaction (PCR) in unstimulated cervical samples. 2. cell-mediated response (cytotoxic T cell response) to HPV 16 infections in association with initial HPV 16 infection as well as persistent infection or clearance. 3. correlations between humoral and cell-mediated response to HPV infections in association with initial HPV infection as well as persistent infection or clearance. Humoral response will be measured by antibody response to HPV type-specific virus-like particles and cell-mediated responses will be measured by local cytokine production and for HPV 16, by cytotoxic T-cell assays. 4. cytokine responses to repeat incident infections with HPV in women who were shown to have primary infections. 5. the role of cervical immaturity in the acquisition of HPV, as well as the relationship between cytokine milieu, response to HPV and degree of cervical immaturity, defined by areas of early to mid squamous metaplasia.
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