Vitamin D status modulates high-risk human papillomavirus infection and persistence: a systematic review and meta-analysis

High-risk human papillomavirus (hr-HPV) infection is the principal cause of cervical cancer worldwide. Emerging evidence suggests that serum 25-hydroxyvitamin D [25(OH)D], a key immunomodulatory biomarker, may influence susceptibility to HPV infection and its persistence; however, findings remain inconsistent. In this study, we conducted a systematic review and meta-analysis to evaluate the association between serum 25(OH)D levels and cervicovaginal hr-HPV infection in women. A comprehensive literature search of PubMed, Scopus, Web of Science, and Google Scholar was performed for studies published between 2003 and 2024. Study quality was assessed using Joanna Briggs Institute (JBI) criteria, and pooled odds ratios (ORs) were estimated using a random-effects model. Nine studies comprising 11,401 participants met the inclusion criteria, of which six were included in the quantitative synthesis. Vitamin D sufficiency was associated with significantly reduced odds of hr-HPV infection (OR = 0.15; 95% CI: 0.03–0.70; p = 0.016), although substantial heterogeneity was observed (I² = 98.3%). The pooled prevalence of hr-HPV infection was 27.63%, while vitamin D deficiency was present in 40.03% of participants. These findings suggest a potentially novel, stage-specific role for vitamin D in modulating HPV persistence rather than initial acquisition, possibly through effects on local immune responses and viral clearance. Optimizing vitamin D status may represent a complementary, host-directed strategy to reduce the progression of hr-HPV-related cervical disease; however, further well-designed longitudinal studies are required to confirm causality and clarify underlying mechanisms.