Background: Angiolymphatic invasion (ALI) and perineural invasion (PNI) are considered poor prognostic indicators in head and neck squamous cell carcinoma but their impact on prognosis in human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is unknown. Adverse prognostic factors in other head and neck cancer subsites have not been found to have the same significance in HPV+ OPSCC. Therefore, we hypothesized that there would be no association between presence of ALI and PNI in surgically-treated HPV+ OPSCC.
Methods: This is a retrospective review of all HPV+ OPSCC patients treated at the University of Pittsburgh Medical Center between 1980-2015. Only those with at least 1 year of follow-up were included. All patients were surgically treated (primary resection and neck dissection) with risk-adjusted adjuvant chemo/radiotherapy for a homogenous patient population. Only those patients with assessment of both ALI and PNI on pathology were included. Kaplan-Meier disease-free survival curves were generated for both ALI and PNI. Patients were then stratified as having 0 risk factors (no ALI or PNI (ALI/PNI score=0)), 1 risk factor (ALI or PNI (ALI/PNI score=1)) and 2 risk factors (both ALI and PNI (ALI/PNI score=2)) and Kaplan-Meier survival curves were generated. Multivariate analysis was performed using a Cox proportional hazard model.
Results: 180 patients were identified meeting inclusion/exclusion criteria. Angiolymphatic invasion was identified in 85/180 (47.2%) and perineural invasion was identified in 31/149 (17.2%). Patients had ALI/PNI scores of 0 (85/180, 47.2%), 1 (74/180, 41.1%), 2 (21/180, 11.7%). The overall recurrence rate was 22/180 (12.2%). The presence of ALI inferred a hazard ratio (HR) of 6.1 for recurrence (p=0.0002). PNI inferred a HR of 3.07 (p=0.01). Patients with either of ALI/PNI had a HR of 5.3 while both ALI/PNI inferred a HR of 12.2, despite a higher prescribed dose of adjuvant radiation with escalating ALI/PNI score (3800 vs. 4900 vs. 5700 cGy, p=0.0008) and chemotherapy (36% vs. 65% vs. 58%, p=0.001). ALI/PNI score remained significantly associated with disease-free survival on multivariate analysis controlling for T-stage, N-stage, radiation dose, use of chemotherapy (HR 6.8, p=0.004).
Conclusion: The presence of either ALI or PNI is associated with a worse prognosis in surgically-treated HPV+ OPSCC and the combination is additive. This work has implications for adjuvant therapy planning.