Improved Survival of HPV ‐Related Sinonasal Squamous Cell Carcinoma With Chemoradiation Treatment

ABSTRACT Objective Human papillomavirus‐related (HPV+) sinonasal squamous cell carcinoma (SNSCC) is associated with improved overall survival (OS) compared to similarly staged HPV‐negative SNSCC. However, data on treatment‐specific outcomes remain limited. Methods We analyzed the National Cancer Database (NCDB) for all SNSCC cases diagnosed between 2010 and 2017 with available HPV testing data. Prognostically significant variables were identified via multivariable Cox regression. Propensity score‐matched cohorts were then created, matching HPV‐positive and HPV‐negative patients exactly by treatment modality and other significant prognostic factors. The association between HPV status and 5‐year OS was assessed across treatment strategies. Results A total of 1697 HPV‐tested SNSCC cases were identified; 551 (32.5%) were HPV+. Multivariable Cox regression showed that HPV status, age, comorbidity score, tumor size, lymphovascular invasion, stage, and surgical margin status were significantly associated with outcomes. Within the propensity score‐matched cohort, HPV positivity was significantly associated with improved OS among patients treated with chemoradiation (HR = 0.55; 95% CI = 0.35–0.87, p = 0.01). No survival benefit was observed in patients treated with surgery alone (HR = 0.85; 95% CI = 0.35–2.04, p = 0.71), surgery with radiation (HR = 1.38; 95% CI = 0.64–3.02, p = 0.41), radiation alone (HR = 0.40; 95% CI = 0.11–1.41, p = 0.16), or in the combined group of these three treatment strategies (HR = 0.97; 95% CI = 0.57–1.62, p = 0.90). Conclusion These findings suggest that HPV+ SNSCC may be particularly sensitive to chemoradiation. Routine HPV testing may be warranted to investigate if tailored treatment approaches focusing on chemoradiation may benefit patients with HPV+ SNSCC.