Prognostic Value of Radiographically-Defined Extranodal Extension is Modulated by Human Papillomavirus Status in Locally Advanced Oropharyngeal Carcinoma

Abstract

Risk-stratification based on clinical and pathologic factors is central to the management of head and neck cancers. The prognostic value of extranodal extension (ENE) in the setting of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) has been questioned. Using radiologic criteria for the presence of ENE we examined its value in HPV-related and unrelated OPSCC. Consecutive patient records from a single institution were identified by pathologic diagnosis of OPSCC and reviewed for appropriateness for further analysis. Records contained information on HPV status and nodal disease with adequate pre-treatment radiographic evaluation. The presence and extent of ECE was determined at time of diagnosis by neuroradiology as reflected by their reports. HPV status was assayed by in-situ hybridization, p16 immunohistochemistry, or both. Kaplan-Meier methods and Cox regression were used to assess the impact of ENE on survival and disease progression. 212 patients with OPSCC diagnosed between April 2008 and December 2014 were included for analysis with median follow-up of 3.3 years. Median age was 58.5 years, 168 patients (79%) had HPV-associated disease, and were predominantly stage IVA (87%). 98% of patients received definitive radiation therapy, and 92% concurrent chemotherapy. Group stage did not differ significantly based on ENE status. Overall, 42 deaths were reported, and 42 patients demonstrated disease progression, accounting for 56 overall events. In patients with HPV-unrelated OPSCC, ENE was associated with a higher rate of death (54.5% vs 31.8%), and overall events (54.5% vs 40.9%). For HPV-related disease, rate of death (24% vs 20.7%) and overall events (16.3% vs 16.1%) were not significantly associated with ENE. In HPV-associated OPSCC, radiographic ENE was not correlated with a higher rate of deaths or overall events. As expected for classic oropharyngeal cancer, ENE was associated with a higher mortality and total events.