The prevalence of anal carcinoma is greatly increased in HIV+ men (35 per 100,000) and HIV+ men who have sex with men (70 per 100,000) relative the general population (0.8 per 100,000). De- spite the need for effective anal carcinoma screening, the workload and costs involved prevent its wide- spread integration into routine HIV care. The candidate is an Assistant Professor with a background of training in Infectious Disease and HIV clinical research. His long-term goal is to develop an HIV clinical research career focusing on the epidemiology, prevention, and treatment of HPV-related anal carcinoma. In his career development, the candidate will acquire didactic training through completion of a Master's of Clinical Research degree that will complement his prior training and aid in completing his research objectives. Practical experience will be gained through completion of the proposed research. The research objective is to develop a predictive model to identify patients with a high risk for progression of early anal dysplasia. The central hypothesis is that progression from low-grade to high-grade dysplasia is associated with environmental, virological, and host molecular factors including: smoking, viral load, viral oncogene expression, p53, p16'nk4a, and Ki67 ex- pression.
Specific aims are to: 1) identify factors associated with progression from low-grade to high-grade anal dysplasia and 2) to develop a statistical model to predict this progression using logistic regression and classification and regression tree analysis.
These aims will be accomplished using a prospective observa- tional study of patients with low grade dysplasia. Environmental, virological, and molecular factors will be assessed at baseline with follow-up at 6 month intervals to assess for progression. This project is expected to have a positive impact on public health by improving the cost-effectiveness of anal dysplasia screening, identifying a population that may benefit from early treatment interventions, and providing information appli- cable to the screening and treatment of other HPV-related cancers. The rationale is that the proposed research will provide the candidate with research skills, a background in HPV research, a publication record in HPV, and information that will form the basis for his ap- plication for independent R01 funding. The candidate is well positioned to capitalize on a K Award based on his prior training and research experience, a team of highly qualified mentors with expertise in epidemiology and HPV-related carcinogenesis, and the commitment of a supportive institutional environment with other funded researchers doing complementary research.