Treatment Modality and Survival in Human Papillomavirus (HPV)-Stratified Early-Stage Oropharyngeal Cancer: A Population-Based Propensity Score-Matched Analysis.

BACKGROUND: Whether treatment modality effects on survival differ by human papillomavirus (HPV)/p16 status in oropharyngeal squamous cell carcinoma (OPSCC) remains unresolved at the population level. A propensity score-matched analysis was performed using data from 9,884 patients with Stage I-II OPSCC identified from the Surveillance, Epidemiology, and End Results (SEER) database (2018-2021). Chemoradiotherapy (CRT) vs. surgery (1:1) and CRT vs. radiotherapy (RT) alone (1:2) were compared, stratified by p16 status. A likelihood ratio test formally tested the treatment×HPV interaction on disease-specific survival (DSS). RESULTS: Surgery was associated with superior overall survival (OS) (hazard ratio (HR) 0.75, 95% CI 0.65-0.87) and DSS (HR 0.59, 0.49-0.72) versus CRT. RT alone was inferior (OS HR 1.55, DSS HR 1.38). The treatment×HPV interaction was non-significant for surgery (DSS p=0.705) and RT alone (DSS p=0.090). In Stage III-IV, no surgical advantage was observed. CONCLUSIONS: Surgical treatment is associated with superior survival in Stage I-II OPSCC irrespective of HPV status. HPV status does not modify the relative effect of treatment modality. RT alone was markedly inferior to CRT in p16-positive Stage II disease.