IMPORTANCE Recently, the American Joint Committee on Cancer (AJCC) updated its staging system for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). The prognostic significance of perineural invasion (PNI) and angiolymphatic invasion (ALI) within this staging system is unknown. OBJECTIVE To examine the prevalence and prognostic significance of PNI and ALI in HPV-positive OPSCC. DESIGN, SETTING, AND PARTICIPANTS A retrospective reviewwas performed of all patients with HPV-positive OPSCC treated surgically at the University of Pittsburgh Medical Center from January 1, 1980, through December 31, 2015, with at least 1 year of follow-up or death within 1 year. INTERVENTIONS Surgical treatment of HPV-positive OPSCC. MAIN OUTCOMES AND MEASURES The prevalence of PNI and ALIwas determined from review of pathologic data, and Kaplan-Meier curves were generated for overall survival and disease-free survival when stratified by the presence of PNI and ALI. Multivariate analysis was performed using a Cox proportional hazards regression model. RESULTS A total of 201 patients met the inclusion criteria (mean [SD] age, 57.4 [9.0] years; 79.6%[3.0%] male, and 20.4%[3.0%] female). Perineural invasion was identified in 32 of 201 primary specimens (15.9%), whereas ALI was identified in 74 of 201 primary specimens (36.8%). Both were significantly associated with increasing T stage. On multivariate analysis, the presence of at least 1 risk factor was significantly associated with overall and disease-free survival (overall hazard ratio, 2.78; 95%CI, 1.15-6.76; disease-free survival hazard ratio, 3.10; 95%CI, 1.17-8.23). Among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of at least 1 risk factor was associated with worse overall survival (hazard ratio, 11.7; 95%CI, 1.2-111.7). CONCLUSIONS AND RELEVANCE Both PNI and ALI were commonly found in HPV-positive OPSCC, with increasing prevalence as T stage increased. The presence of at least 1 risk factor was associated with worse overall and disease-free survival. Specifically, among patients classified as having stage II disease according to the eighth edition of the AJCC manual, the presence of ALI or PNI may suggest a poorer prognosis.
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