Abstract
Background/Objectives: Vitamin D is classically associated with calcium and phosphate homeostasis, but recent research has expanded its role to include several new roles such as immune regulation, inflammation, and potential anti-cancer properties. The vitamin D receptor (VDR) is expressed in over 400 tissues, including those of the head and neck, implying a potential link between vitamin D and head and neck cancers (HNCs). Given the need for newer and better therapeutic approaches, this systematic review aims to synthesize existing clinical evidence on the relationship between vitamin D status and clinical outcomes in HNC patients. Methods and Results: A comprehensive literature search, across multiple databases including PubMed, Google Scholar and Science Direct, identified 187,642 studies related to vitamin D and cancer, from which 16 studies met the inclusion criteria. The inclusion criteria were English-language, full-text original research (2015-2025) on vitamin D's role in HNC progression and treatment, focusing on human studies. The findings indicate that vitamin D deficiency is highly prevalent among HNC patients, with rates ranging from 47% to 95%, particularly in advanced-stage cancers and those undergoing intensive treatment. Inverse association between vitamin D levels and HNC risk was reported, with higher serum 25(OH)D levels linked to a 30-32% reduction in cancer risk. Additionally, higher vitamin D levels correlated with improved survival rates and reduced recurrence, though some findings lacked statistical significance. Deficiencies were associated with higher rates of malnutrition and postoperative complications, reinforcing vitamin D's role in nutritional stability and surgical recovery. Conclusions: This systematic review highlights how common and significant vitamin D deficiency is among head and neck cancer (HNC) patients, exploring its possible role in cancer risk, prognosis, survival, treatment-related side effects, malnutrition, and post-surgical complications. The evidence suggests that while higher vitamin D levels are linked to better survival and fewer treatment-related issues, the benefits seem to level off beyond a certain point, indicating a more complex relationship. Additionally, vitamin D supplementation appears to help reduce chemoradiation side effects like mucositis, skin toxicity, dysphagia, and pain, ultimately improving patients' quality of life during treatment.