Evaluation of Pathology-Based Staging for HPV-Associated Squamous Cell Carcinoma of the Oropharynx in a Large National Sample

Abstract

Metastatic node number ≥ 5 has been identified by small retrospective studies as a prognostic indicator of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV-A OPC). We aimed to validate the prognostic value of metastatic node number and the revised American Joint Committee on Cancer (AJCC) 8thedition pathologic and clinical nodal staging system in a large national sample. The National Cancer Database was used to identify patients with HPV-A OPC (any T, any N, M0) treated with curative-intent primary surgery +/- adjuvant therapy from 2010-2013. Demographic and clinicopathologic predictors of survival were analyzed by the chi-square test and logistic regression. OS was evaluated using Cox proportional hazard regression model, Kaplan-Meier method, log-rank statistic, and propensity score matching. Harrells’ concordance index (c-index) was determined to measure the discriminatory power across the AJCC 8thedition pathologic and clinical staging systems. We identified 2,347 patients. Median follow up was 33.6 months. 3-year OS of the AJCC 8th edition pathologic stage I, II, and III patients was 96.3%, 87.3% and 76.7%, respectively (log-rank p<.001). On multivariable logistic regression, patients with ≥ 5 metastatic nodes were more likely to have higher pT stage (odds ratio [OR] 2.14, 95% confidence interval [CI] 1.43-3.19, p<.001), pathologic extranodal extension (pENE) (OR 3.39, 95% CI 2.51-4.57, p<.001), and lymphovascular invasion (LVI) (OR 1.30, 95% CI 1.08-1.56, p.006). After adjusting for age, comorbidity, pT stage, pENE, surgical margins, LVI, adjuvant treatment, and insurance status, having ≥ 5 metastatic lymph nodes was associated with inferior OS compared to those with ≤ 4 nodes on multivariable Cox regression (HR 1.81; 95% CI 1.14-2.88; p=.011). Propensity score matching yielded a well-matched cohort of 486 patients and redemonstrated inferior OS in the ≥ 5 metastatic node group (HR 2.91, 95% CI 1.98-4.29, p<.001). The c-indices for the revised pathologic and clinical nodal staging in a multivariable model were 0.72 and 0.70, respectively. Using a large national sample, we have validated metastatic node number ≥ 5 as a significant prognostic marker in HPV-A OPC on multivariable and propensity score-matched analyses. The AJCC 8th edition revisions to both pathologic and clinical staging appear to reliably establish prognosis in this large patient cohort.