Background Head and neck squamous cell carcinoma (HNSCC) is more prevalent in men than women and this disparity cannot be fully explained by known risk factors. Recent studies have shown that loss of Y chromosome (LoY) confers an increased risk of solid cancer and reduces life expectancy in men. Methods Using publicly available data from The Cancer Genome Atlas, we investigated the prevalence of LoY and its association with clinicopathological features in male HNSCC. Results LoY was detectable in around 25% of male HNSCC. Men with human papillomavirus‐negative tumors exhibiting LoY experienced significantly worse overall survival than those with no LoY. Moreover, LoY tumors exhibited overexpression of genes involved in redox processes, including genes previously implicated in resistance to both radiotherapy and cisplatin‐based chemotherapeutics. Conclusion LoY may be an indicator of poor prognosis in male HNSCC that is linked to the overexpression of genes associated with resistance to standard care therapies.
