Interactions between serum folate and human papillomavirus with cervical intraepithelial neoplasia risk in a Chinese population-based study

Although folate deficiency has long been implicated in cancer development, uncertainties remain concerning its role in cervical cancer prevention. In particular, the interaction between human papillomavirus (HPV) and folate in the risk of cervical intraepithelial neoplasia (CIN) has been little studied. The goal of this study was to evaluate the dose-response association of serum folate with the risk of CIN, and the potential for HPV to modify the risk of CIN. We performed a cross-sectional analysis of screening data in 2304 women aged 19–65 y who participated in an ongoing cohort of 40,000 women in China. Both categoric and spline analyses were used to evaluate the dose-response relation between serum folate and CIN risk. After adjusting for potential confounders, a statistically significant inverse association between serum folate concentration and at least grade 2 CIN (CIN2+) risk was observed (1st quartile compared with 4th quartile: OR = 1.40; 95% CI: 1.09, 1.79; P-trend < 0.01); however, serum folate concentration was not associated with CIN1 risk. The risk patterns are similar when limited to only CIN2 and CIN3. An inverse linear relation between increased serum folate concentration and the risk of higher-grade CIN (CIN2, CIN3, and CIN2+) was also observed (for CIN2+: P-overall < 0.01, P-nonlinearity = 0.96). The highest risk of CIN2+ was observed in women with high-risk HPV types, who also had the lowest serum folate concentrations (P-interaction < 0.01). Our study indicates that serum folate is inversely associated with the risk of higher-grade CIN in Chinese women either with or without high-risk HPV infection. Thus, maintenance of normal serum folate levels may prove important for reducing the risk of CIN in women.