Association of antioxidant nutrients and human papillomavirus persistence, clearance and viral load among women in the Ludwig-McGill Cohort Study

Abstract

Although an oncogenic human papillomavirus (HPV) infection has been established as the necessary cause of cervical cancer, most HPV infections are transient and rarely progress to significant cervical lesions. Current research has focused on identifying factors associated with viral persistence and clearance. Low nutritional status might influence a woman's risk of having a persistent HPV infection and progression of that infection to cervical dysplasia, or at higher levels increase the probability of clearing infections. The overall goal of this research was to determine the associations between serum carotenoid, tocopherol, and retinoic acid levels and cervical carcinogenesis among the Ludwig-McGill Cohort Study. A sub-cohort of 846 women, all of whom had HPV results available from four consecutive study visits in the first year of follow-up, had serum samples analyzed for circulating nutrients. We determined the variability of circulating retinoic acid levels over the four months in a sample of 502 women and identified lifestyle, demographic and nutritional factors that were associated with these levels. The relative abundance of retinoic acid isomers was similar for each visit and the within person-variability of total retinoic acid and individual isomers was low. Using multivariate logistic regression models that serum nutrient levels (retinol, β-carotene, and β-cryptoxanthin), age, race, oral contraceptive use, total number of pregnancies, and season of initial blood draw were significantly associated with endogenous retinoic acid isomer levels. Among the 407 HPV positive women, endogenous levels of all-trans retinoic acid were positively associated with an increased probability of clearing oncogenic and nononcogenic type-specific HPV infections. Furthermore, among the carotenoids and tocopherols examined, we found that higher circulating zeaxanthin concentrations were associated with increased probability of clearing type-specific oncogenic HPV infections. Inverse associations were found between serum tocopherol levels (α-, δ- and γ-tocopherol) and type-specific nononcogenic HPV persistence. Overall, the findings of this study suggest that women with the highest levels of serum all-trans retinoic acid, zeaxanthin, and tocopherol are at a decreased risk for a persistent, type-specific HPV infection of long duration. As both classes of nutrients are modifiable by diet, alterations in diet may be a safe approach to cervical cancer prevention.