Association between vitamin D deficiency and longitudinal risk of head and neck cancer: a multi-institutional retrospective study
Abstract
Background Vitamin D is implicated in cancer biology through its regulation of cellular proliferation, apoptosis, and immune surveillance; however, evidence linking vitamin D deficiency (VDD) to head and neck cancer (HNC) risk remains limited by small sample sizes and inadequate control for confounders. Methods Using the TriNetX Global Collaborative Network, we conducted a retrospective cohort study comparing adults with laboratory-confirmed VDD (25-hydroxyvitamin D 50 years but absent in younger adults (p for interaction <0.001). Sensitivity analyses with extended landmark periods and alternative cohort definitions yielded consistent results. Conclusion In this observational study, VDD was significantly associated with an increased risk of HNC, with consistency across subtypes and a dose–response gradient. However, the observational design precludes causal inference, and residual confounding cannot be fully excluded. Prospective studies with detailed lifestyle data are needed to confirm these findings.
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 108,010 participants or records.
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