Preliminary analyses from the past three years of funding indicate that dietary and serum carotenoids, potent antioxidants, are independently associated with type-specific HPV persistence. Our observations of a reduced risk of persistent infection with compounds that quench reactive oxygen species combined with a growing literature demonstrating increased risk of cervical disease with factors that generate reactive oxygen species, lead us to hypothesize that the oxidant: antioxidant ratio may influence the natural history of HPV infections and hence disease progression. The overall goal of this application is to determine, using prospectively collected HPV and cytology data, the association between markers of oxidant load and cervical carcinogenesis among women in the Ludwig- McGill HPV Natural History Study. This project will provide the first prospective analysis of the association between markers of oxidant load [e.g., malondialdehyde and anti-5-hydroxymethyl-2'-deoxyuridine autoantibodies (anti-HMdU aAb)] and risk for persistent HPV infection that utilizes sensitive and specific methods for assessing type of HPV infection over a 36-month period. In addition, we will prospectively determine risk of progression to SIL over a 5-year period associated with markers of oxidant load. This study is unique in that it focuses on early events in cervical carcinogenesis: HPV infection, HPV persistence, and progression to SIL. It is cost effective utilizing previously collected serum samples and questionnaire and antioxidant nutrient data. The study utilizes state of the art methods for determining both HPV status and oxidant load status. Furthermore, it incorporates multiple measurements of HPV status, factors that contribute to oxidant load, and oxidant load, lessening the probability that measurement imprecision resulting from temporal fluctuations will obscure the total association.
