___^__^^_The observation that HPV-related cancers may be linked to immunosuppression has led us to focus thiscompetitive renewal on a population that is receiving strong immunosuppressive drugs for extended periodsof time, i.e., renal and cardiac organ transplant patients (OTR). These patients experience a high incidenceof what may be an HPV-associated cancer, squamous cell skin cancer (SCSC). We posit that transplantpopulations are the best model to study the effect of immunosuppression on HPV infection and theassociation between HPV and SCSC because transplant patients are now living longer with theirtransplants,the prevalence of SCSC sharply increases with time since transplant, these patients often have multiple andaggressive SCSC tumors, and SCSC will ultimately affect the majority of transplant patients. In this projectwe propose two complementary but separate population-based studies to investigate the role of HPV in renaland cardiac OTR. The first study we propose is a nested case-control study that will be able to assess 1) ifthere are high-risk genus beta HPV types that are associated with an increased risk of SCSC; 2) whetherpre-transplant HPV antibodies predict SCSC; and 3) if patient risk factor data (including history of sunexposure, skin type, eye color, medication use, and other exposures) gathered in an in-person interview andintegrated with measures of genus beta HPV types together predict which patients are at increased risk ofSCSC. The second study is a longitudinal study designed to explore the kinetics of HPV infection withrepeated sample collection over a 2-year period, starting with a pre-transplant sample. All patientstransplanted in 2008 and 2009 who are residents of the local area will be invited to participate. In thislongitudinal study we will assess 1) whether the number of HPV DNA types, antibody response, or viralpersistence increases with time since transplant and 2) the effect of changes in levels of cell-mediatedimmunity on HPV infection status (as measured by various markers of HPV) over time. Our HPV ProgramProject group has a long track record of interdisciplinary collaboration, and we plan to develop a newdirection for our work that employs recently developed laboratory techniques that are specific to studyinggenus beta HPV types.. Our studies may contribute to a more complete understanding of the role of genusbeta HPV types in SCSC and the role immunosuppression plays in HPV activation. If a strong link betweenspecific HPV types and SCSC can be verified, there may be evidence to suggest clinical trials of HPVvaccines to modify the risk of SCSC in OTR.Lay Summary: This study will examine the risk of squamous cell skin cancer and its relationship to humanpapillomavirus in a high-risk group. If a clear association can be shown in this study and others like it, futurework could explore prevention and treatment of this type of skin cancer in different populations.
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