LAUSR

PURPOSE Recent pathologic staging of HPV-positive oropharyngeal squamous cell carcinomas (OPSCC) is solely dependent on number of pathologic nodes. Using a large dataset, we aimed to understand how increase in pathologic lymph nodes (LN) associated with overall survival. MATERIALS AND METHODS National Cancer Database was queried for HPV-positive OPSCC patients undergoing primary surgery with LN dissection between 2010 and 2013. Kaplan-Meier, univariate and multivariate Cox models were used to evaluate overall survival. Interaction between nodal status and radiotherapy was examined. RESULTS Implications of pathologic LN on overall survival differed according to receipt of post-operative radiotherapy (p-valueinteraction = 0.008). In patients who did not receive adjuvant radiotherapy, there were no significant differences in risk of death from 0 to 2 pathologic nodes (adjusted HR (aHR) 0.92, 95%CI 0.61-1.4). However, risk increased by 18% on average with each additional LN thereafter (aHR 1.18, 95%CI 1.1-1.27). Among radiotherapy patients, after adjusting for other variables, patients with 1 pathologic LN had 70% lower risk of death than those with 0 pathologic LN (aHR 0.30, 95%CI 0.14-0.64). Thereafter, risk increased on average by 7% with each additional LN (aHR 1.07, 95%CI 1-1.14). CONCLUSION The prognostic impact of pathologic nodes in resected HPV-positive OPSCC differs by receipt of radiotherapy, with better outcomes in post-operative radiotherapy treated patients with one pathologic LN than none. These findings suggest that LN involvement may improve anti-tumor immune responses following radiotherapy, or result in earlier detection and treatment of disease. These results merit further studies to corroborate these findings and establish the underlying mechanism.