Unraveling the Puzzle: a Systematic Review of the Carcinogenic Role of Arsenic in Head and Neck Cancers.

Arsenic exposure has been implicated in various malignancies, including head and neck cancers (HNCs). However, the association between arsenic exposure and HNC development remains unclear. This systematic review aimed to assess the relationship between arsenic exposure and the risk of developing HNCs. This study adhered to PRISMA guidelines. A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted from inception to January 2025 to identify relevant studies. Observational studies reporting the association between arsenic and HNCs were included. Two independent reviewers performed study selection, data extraction, and risk of bias assessment using the NIH criteria. A total of 24 studies met the eligibility criteria, including 35,641 cases and 4,631 controls. The mean age of cases was 50.3 years, while controls had a mean age of 57.7 years. Nineteen studies assessed nasopharyngeal/laryngeal cancers, and 13 investigated oral cancers. Environmental/occupational arsenic exposure was reported in 14 studies, while 11 studies measured arsenic levels in biological samples. Geographical differences in exposure outcomes were observed, with significant associations reported in studies from Tunisia, Chile, Brazil, and Taiwan, while studies from the UK, Finland, and a multicenter European study found no significant relationship. Blood, hair, soil, and drinking water arsenic concentrations varied across studies, with inconsistent findings. The findings suggest a potential link between arsenic exposure and HNCs, particularly in regions with high environmental contamination. However, heterogeneity in exposure assessment and study design limits definitive conclusions. Further well-controlled studies are needed to clarify the association and underlying mechanisms.