The prognostic impact of pathologic lymph nodes in HPV-positive oropharyngeal cancers

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-value_interaction = 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.