Bauer E, et al. - Researchers analyzed a retrospective cohort of cases diagnosed with human papillomavirus–positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC) from 2010 to 2015 in the National Cancer Database in order to comprehensively investigate extranodal extension (ENE) as a prognosticator. All OPSCC HPV-positive cases with appropriate International Classification of Diseases-0-3 codes that received surgery with a neck dissection were included. Observations revealed the highest 5-year survival for cases that were ENE-negative and the lowest 5-year survival for ENE-positive cases. They noted an increased risk of death in correlation to nodal (N) category 1, ENE-positive status compared with N1, ENE-negative status. Compared to node-positive/ENE-negative status, both microscopic and macroscopic ENE were correlated to worse outcomes. To develop and discuss treatment plans for HPV-positive OPSCC, the American Joint Committee on Cancer 8th edition staging system affords a much-improved framework. They recommend carefully considering the importance of ENE in these patients.