OBJECTIVE: To compare survival outcomes between primary surgery and primary radiation therapy (RT) in patients with human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC). STUDY DESIGN: A retrospective observational cohort study. SETTING: National Cancer Database. METHODS: A National Cancer Database review was conducted of 2635 patients with HPV-negative OPSCC who underwent surgery or RT +/- chemotherapy between 2010 and 2014. Univariate analysis was performed on all variables and entered into a multivariate model. The main outcome was overall survival (OS). RESULTS: A total of 2635 patients with HPV-negative OPSCC were organized into 4 groups based on cancer staging. In group 1 (T1-2 N0-1; n = 774), up-front surgery had significantly better 5-year OS (76.2%) than RT (56.8%; adjusted hazard ratio [aHR], 1.76; P = .009; 95% CI, 1.15-2.69) and chemoradiation therapy (CRT; 69.5%; aHR, 1.56; P = .019; 95% CI, 1.08-2.26). In group 2 (T3-4 N0-1; n = 327), no significant difference existed between surgery and CRT (5-year OS, 51.3% vs 52.4%; aHR, 0.96; P = .88; 95% CI, 0.54-1.69). In group 3a (T1-2 N2-3; n = 807), surgery with adjuvant treatment showed significantly better 5-year OS than CRT (78.6% vs 68.8%; aHR, 1.51; P = .027; 95% CI, 1.05-2.18). In group 3b (T3-4 N2-3; n = 737), surgery with adjuvant treatment was not statistically associated with better 5-year OS as compared with CRT (61.0% vs 43.7%; aHR, 1.53; P = .06; 95% CI, 0.98-2.39). CONCLUSION: Primary surgery may provide improved survival outcomes in many cases of HPV-negative OPSCCs. These data should be used in weighing treatment options and may serve as a basis to better delineate treatment algorithms for HPV-negative disease.
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