The objective of this study is to develop a predictive model to identify patients who are at greatest risk for progression of anal intraepithelial neoplastic changes. The central hypotheses are: 1) that progression of early HPV-related anal dysplasia is associated with environmental, virological, and host molecular factors and 2) that it is possible to develop a predictive statistical model with a high sensitivity and specificity for predicting disease progression. These hypotheses have been formulated on the basis of strong evidence from studies of HPV-related cervical dysplasia that smoking, HPV E2 expression, HPV E6/E7 protein expression, high-risk HPV type, HPV viral load, p16 expression, p53 expression and Ki67 expression are associated with progressive cervical dysplasia. The rationale for the proposed research is that development of a predictive model will allow clinicians to design more cost-effective screening and follow-up strategies which focus resources on intensively testing only those patients with a significant risk for progression. Further, the models developed will allow clinicians to identify a population of patients who may benefit from early treatment interventions. Finally, information learned from this research may provide information applicable to other HPV-related cancers.