Epidemiologic research conducted over the past couple of decades has shown that infection with the human papilloma virus (HPV) is a cause of most cases of cervical cancer. Prospective studies have shown that women infected with HPV are more likely to develop cervical intraepithelial neoplasia (CIN), and that those with persistent oncogenic type HPV infections are at a significantly increased risk of developing CIN compared with women transiently infected. In addition, persistently HPV positive women appear to be four times more likely to have persistent cervical lesions. Although HPV infection is a cause of cervical cancer, it may be an insufficient cause requiring the presence of other factors for the infection to progress to a significant cervical lesion. Nutritional status may be an important cofactor affecting both HPV persistence and progression of persistent HPV infection to CIN. However, the association between nutritional status and cervical carcinogenesis has not been adequately tested. The overall goal of this application is to determine, using prospectively collected HPV and cytology data, the association between serum carotenoid and tocopherol status and cervical carcinogenesis among a cohort of high risk study participants in the Brazilian HPV Natural History Cohort (RO1 CA70269). This project will provide the first prospective analysis of serum carotenoid and tocopherol concentrations and risk for persistent HPV infection; it will be based on sensitive and specific methods for assessing type of HPV infection over a 12 month period, and evaluate subsequent 5 year risk of progression to CIN. This proposed study is unique in that if focuses on early events in cervical carcinogenesis: HPV infection, HPV persistence, and progression to CIN. It is cost-effective, utilizing previously collected serum samples and questionnaire data. The study utilizes state of the art methods for determining both PV status and serum carotenoid and tocopherol status. Furthermore, it incorporates multiple measurements of both HPV status and serum nutrient concentrations minimizing the probability that measurement imprecision resulting from temporal fluctuations will obscure the true association between nutrients status, and HPV persistence and risk of CIN. Results from this study will efficiently further our understanding of the role of antioxidant nutrients and cervical carcinogens.
