Trimodality therapy for HPV-positive oropharyngeal cancer: A population-based study: Trimodality therapy for HPV+ OPC

Background: Although HPV status is a well-established prognostic factor in oropharyngeal squamous cell carcinoma (OPSCC), approximately 20% of HPV-positive patients die from their disease. We therefore sought to ascertain whether there is a benefit to trimodality therapy with surgery among patients with locally advanced (LA) disease receiving chemoradiation. Methods: The SEER Head and Neck with HPV Status Database identified adult patients with non-metastatic OPSCC between 2013 and 2014 with known HPV status who received chemoradiation as part of definitive treatment. The primary outcome was cancer-specific mortality (CSM) for locally-advanced (LA) (T3-T4, or N2-N3, per AJCC 7) versus early-stage (ES) (T1-T2 and N0-N1) disease, stratified by HPV status. The secondary outcome was overall survival (OS). Results: Among 2974 patients who met study criteria, 671 patients (22.6%) received upfront surgery (trimodality therapy). In the LA setting, there was a significant reduction in CSM with trimodality therapy compared to chemoradiation alone in HPV-positive (Adjusted Hazard Ratio [AHR] 0.19, 95% Confidence Interval [CI] 0.04–0.80; P = 0.024), but not HPV-negative disease [P_interaction = 0.04]. There was no benefit to trimodality therapy for ES disease, regardless of HPV status. There was also an improvement in OS with trimodality therapy for HPV-positive LA patients (AHR = 0.28, p = 0.006, 95% CI = 0.11–0.70). In contrast, trimodality therapy was not associated with improved OS for HPV-negative patients regardless of stage. Conclusions: HPV status may predict for improved outcomes with surgery/trimodality therapy in LA OPSCC. Our findings support prospective investigations to optimize care for the subset of HPV-positive patients who are at greatest risk of cancer death, where trimodality therapy may be appropriate.