Examining the Interaction Between Sex and Race in Outcomes of Head and Neck Squamous Cell Carcinoma

ABSTRACT Background This study elucidated sex disparities in head and neck squamous cell carcinoma (HNSCC) outcomes and investigated their interaction with race. Methods A total of 452 patients diagnosed with HNSCC were grouped by sex and race. Survival was analyzed using Kaplan–Meier curves with log rank tests and multivariable Cox models to assess sex/race associations while adjusting for confounders. Results Males were more likely to have advanced‐stage cancer (79.6%, n = 257 vs. 70.5%, n = 91; p = 0.040). African American females had the best 5‐year overall survival, followed by White females and Hispanic males. African American males had the worst survival ( p = 0.0334). This sex disparity within the African American population persisted when controlling for confounding variables (HR = 0.343; 95% CI: 0.154–0.766; p = 0.0090) and was more pronounced in HPV‐negative cases (HR = 0.184, 95% CI = 0.043–0.786). Conclusions Race‐stratified analysis revealed a survival advantage for African American females over males. Further analysis shows that HPV status, alongside race, moderates the effect of sex on HNSCC outcomes. Level of Evidence 3.