Serum Concentrations of Novel Vitamin D Biomarkers and Detection of Prevalent High-Risk HPV Infection

Introduction: Vitamin D has potential immunomodulating benefits in infection. While one prior population-based cross-sectional study showed a protective association between serum concentrations of 25(OH)D and high-risk HPV (hrHPV) infection, additional biomarkers present at different stages along the vitamin D metabolic pathway may more completely characterize vitamin D status than 25(OH)D alone. We evaluated cross-sectional associations between 25(OH)D and four additional, novel biomarkers and prevalent hrHPV infection among mid-adult women in Seattle, Washington. Methods: We identified stored sera from women 30-50 years old (N=404) enrolled into an HPV natural history study between 2011-2012. Sera were tested for 5 vitamin D biomarkers: 25(OH)D, 1,25(OH)D, 24,24(OH)D, free vitamin D, and vitamin D binding protein (DBP). Using multiple logistic regression, we estimated the cross-sectional association between serum concentrations of vitamin D and cervicovaginal hrHPV detection. Total vitamin D (25(OH)D) was modeled as both a continuous and categorical measure, using clinically-relevant cut-points to indicate sufficiency (≥20ng/mL or ≥30ng/mL). We controlled for biological, demographic, and behavioral characteristics using three stages of adjustment. Effect modification by race (White, non-White) was evaluated, and post hoc analyses examined likely vitamin D supplementation (25(OH)D ≥50ng/mL). Findings: Mean serum concentrations of 25(OH)D were 31.3ng/mL (standard deviation 10.5). Overall prevalence of cervicovaginal hrHPV infection was 22%. 25(OH)D serum concentration was not associated with prevalent hrHPV; modeling the exposure as a categorical variable did not significantly change interpretation. Each 1ng/mL increase in 24,25(OH)D was borderline statistically significantly associated with a higher likelihood of hrHPV infection (aOR 1.23, 95% CI 0.97, 1.55). No significant associations were observed for other biomarkers. There was no evidence of effect modification by race. Women with serum concentrations of 25(OH)D ≥50ng/mL had a higher likelihood of prevalent hrHPV compared to women with levels <50ng/mL (aOR 2.82, 95% CI 1.12, 7.11). Conclusion: In contrast to the prior population-based study, we did not find 25(OH)D serum concentrations were associated with prevalent hrHPV. Higher levels of one novel biomarker, 24,25(OH)D, were associated with increased odds of hrHPV, an unexpected finding. Post hoc analyses warrant further exploration into the relationship between vitamin D supplementation and hrHPV infection.