Location
Moultrie, GA
Start Date
17-4-2026 12:00 PM
End Date
17-4-2026 1:00 PM
Description
INTRODUCTION:
Persistent infection with high-risk human papillomavirus (hrHPV) is the necessary etiologic cause of cervical carcinogenesis and the primary driver of cervical intraepithelial neoplasia (CIN) progression. While HPV oncoproteins E6 and E7 mediate malignant transformation, the contribution of host metabolic and immunological factors to hrHPV persistence and CIN progression remains incompletely characterized. Vitamin D, measured as serum 25-hydroxyvitamin D [25(OH)D], regulates innate and adaptive immune pathways, epithelial differentiation, and inflammatory signaling relevant to HPV immune surveillance. Despite biological plausibility, clinical evidence linking 25(OH)D status to hrHPV persistence and high-grade cervical neoplasia remains inconsistent across study populations and methodologies. This structured narrative review synthesizes current clinical, epidemiological, and mechanistic evidence examining the association between serum 25(OH)D, hrHPV persistence, CIN grade, and progression to high-grade cervical intraepithelial neoplasia (CIN2+).
METHODS:
A structured narrative review was conducted following a predefined search strategy. PubMed/MEDLINE was searched from database inception through March 2026 using combinations of MeSH terms and keywords related to vitamin D ("vitamin D", "25-hydroxyvitamin D", "25(OH)D", "cholecalciferol") and HPV-associated cervical disease ("human papillomavirus", "HPV persistence", "cervical intraepithelial neoplasia", "CIN2+", "cervical dysplasia", "HSIL"). Studies were eligible if they measured serum 25(OH)D in women aged 18-65 undergoing cervical screening or with confirmed hrHPV infection and reported hrHPV persistence, CIN grade, CIN regression, or progression to CIN2+. hrHPV persistence was defined as detection of the same high-risk HPV genotype at ≥ 2 time points ≥ 6 months apart. Vitamin D status was categorized as deficient (< 20 ng/mL), insufficient (20–29 ng/mL), or sufficient (≥30 ng/mL). Cohort, cross-sectional, and randomized studies were included, with mechanistic studies used to contextualize biological pathways. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and the RoB2 tool. Due to heterogeneity across study designs, vitamin D assays, and outcome definitions, findings were synthesized narratively.
RESULTS:
Across included studies spanning seven countries, a predominant inverse association was observed between serum 25(OH)D levels and hrHPV prevalence, cervical dysplasia severity, and CIN2+ risk. The sole randomized controlled trial reported significantly greater CIN1 regression with vitamin D3 supplementation compared with placebo (84.6% vs 53.8%, p=0.01). Contradictory findings included a paradoxical positive association between higher 25(OH)D and short-term hrHPV persistence, as well as a modifying interaction between HIV status and vitamin D on dysplasia grade.
DISCUSSION:
Current evidence suggests that vitamin D insufficiency may impair immune surveillance of hrHPV infection, potentially contributing to persistent infection and progression toward high-grade cervical neoplasia through immunomodulatory and epithelial regulatory mechanisms. Standardized prospective studies with consistent 25(OH)D thresholds and longitudinal HPV clearance outcomes are needed to determine whether vitamin D optimization could serve as an adjunct strategy in cervical cancer prevention.
Embargo Period
10-26-2026
Low Serum 25-Hydroxyvitamin D and High-Grade Cervical Intraepithelial Neoplasia (CIN2+): A Structured Narrative Review
Moultrie, GA
INTRODUCTION:
Persistent infection with high-risk human papillomavirus (hrHPV) is the necessary etiologic cause of cervical carcinogenesis and the primary driver of cervical intraepithelial neoplasia (CIN) progression. While HPV oncoproteins E6 and E7 mediate malignant transformation, the contribution of host metabolic and immunological factors to hrHPV persistence and CIN progression remains incompletely characterized. Vitamin D, measured as serum 25-hydroxyvitamin D [25(OH)D], regulates innate and adaptive immune pathways, epithelial differentiation, and inflammatory signaling relevant to HPV immune surveillance. Despite biological plausibility, clinical evidence linking 25(OH)D status to hrHPV persistence and high-grade cervical neoplasia remains inconsistent across study populations and methodologies. This structured narrative review synthesizes current clinical, epidemiological, and mechanistic evidence examining the association between serum 25(OH)D, hrHPV persistence, CIN grade, and progression to high-grade cervical intraepithelial neoplasia (CIN2+).
METHODS:
A structured narrative review was conducted following a predefined search strategy. PubMed/MEDLINE was searched from database inception through March 2026 using combinations of MeSH terms and keywords related to vitamin D ("vitamin D", "25-hydroxyvitamin D", "25(OH)D", "cholecalciferol") and HPV-associated cervical disease ("human papillomavirus", "HPV persistence", "cervical intraepithelial neoplasia", "CIN2+", "cervical dysplasia", "HSIL"). Studies were eligible if they measured serum 25(OH)D in women aged 18-65 undergoing cervical screening or with confirmed hrHPV infection and reported hrHPV persistence, CIN grade, CIN regression, or progression to CIN2+. hrHPV persistence was defined as detection of the same high-risk HPV genotype at ≥ 2 time points ≥ 6 months apart. Vitamin D status was categorized as deficient (< 20 ng/mL), insufficient (20–29 ng/mL), or sufficient (≥30 ng/mL). Cohort, cross-sectional, and randomized studies were included, with mechanistic studies used to contextualize biological pathways. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and the RoB2 tool. Due to heterogeneity across study designs, vitamin D assays, and outcome definitions, findings were synthesized narratively.
RESULTS:
Across included studies spanning seven countries, a predominant inverse association was observed between serum 25(OH)D levels and hrHPV prevalence, cervical dysplasia severity, and CIN2+ risk. The sole randomized controlled trial reported significantly greater CIN1 regression with vitamin D3 supplementation compared with placebo (84.6% vs 53.8%, p=0.01). Contradictory findings included a paradoxical positive association between higher 25(OH)D and short-term hrHPV persistence, as well as a modifying interaction between HIV status and vitamin D on dysplasia grade.
DISCUSSION:
Current evidence suggests that vitamin D insufficiency may impair immune surveillance of hrHPV infection, potentially contributing to persistent infection and progression toward high-grade cervical neoplasia through immunomodulatory and epithelial regulatory mechanisms. Standardized prospective studies with consistent 25(OH)D thresholds and longitudinal HPV clearance outcomes are needed to determine whether vitamin D optimization could serve as an adjunct strategy in cervical cancer prevention.