This career development proposal describes a five-year training and research plan centered on the role of infection in carcinogenesis to build a foundation for a career in cancer prevention research. The candidate's long term career goal is to combine expertise in epidemiology with methods from clinical research and basic science to lead multidisciplinary efforts to clarify the etiologic role of infection in carcinogenesis, identify individuals at higher risk for progression, and develop decision tools to improve cancer outcomes. This goal will be achieved through rigorous didactic training and research activities to develop the candidate's expertise in: 1) molecular biology of cancer and viral pathogenesis;2) translation of molecular prevention of cancer to health care settings;and 3) design and analysis of longitudinal research. Persistent infection with high-risk types of human papillomavirus (HPV) has been established as a necessary, but not sufficient, factor in cervical carcinogenesis. However, the natural history and mechanism of HPV infection in cervical carcinogenesis remain unclear, in part due to limits in current HPV detection methods. The application of a novel, type-specific method for HPV detection in blood provides a breakthrough opportunity to study aspects of HPV infection that may determine risk of cervical disease. Integration of emerging technology for use in early detection and risk assessment, and translation of these technologies into clinical settings, have been identified as high priorities in the National Cancer Institute's strategy for reducing cancer mortality. The overall scientific goal is to determine how high-risk HPV in blood, in concert with HPV cofactors, correlates with cervical disease over time. This proposal integrates multidisciplinary methods to achieve the following research aims: 1) validate a new technique to detect HPV types 16 and 18 at the cervix (Aim 1);2) identify associations of HPV 16 and 18 detected in cervical specimens with detection of these HPV types in blood (Aim 2);and 3) determine 2-year risk of progression in women with low-grade cervical disease who are positive for high-risk HPV types in their blood at baseline relative to women with negative HPV blood status (Aim 3). Collectively, outcomes of this research will advance our understanding of the relationship of HPV in blood with risk of cervical disease. This research is expected to positively impact public health by facilitating new screening approaches that may ultimately reduce morbidity, mortality, and health care costs.
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