HPV/p16 Positivity and Nodal Status are Associated With Locoregional Control in Penile Cancer

Abstract

Penile cancer (PeCa) is a rare aggressive malignancy that can be associated with the human papillomavirus (HPV). HPV tumor positivity is known to correlate with improved response rates to chemoradiation therapy (CRT) in a number of malignancies. PeCa is often managed by surgical resection and can be treated with adjuvant CRT to improve locoregional control (LRC). Our objective was to identify factors associated with PeCa LRC. We retrospectively identified patients with known HPV status diagnosed with squamous cell carcinoma of the penis that underwent surgical resection between 1999 and 2016. Patients with recurrent or distant metastatic disease were excluded. The relationship between tumor/treatment characteristics and LRC were analyzed with univariate (UVA) and multivariate (MVA) Cox proportional hazard regression analysis. Variables with a trending association with LRC on UVA (p<0.1) were included on MVA. Time to event outcomes were also estimated with Kaplan-Meier and compared via log-rank. There were 51 patients identified with a median follow up of 12 months. Patients were primarily HPV negative (n=28, 55%), pathologic node negative (pN0, 45%), AJCC stage II (43%), treated with partial penectomy (76%), had negative surgical margins (94%), and underwent inguinal dissection (82%). Less commonly, patients were treated with adjuvant CRT (33%) and pelvic dissection (10%). The 1 year LRC rate was 63%. Factors predictive of LRC on UVA included: performance status, tumor stage, nodal stage, HPV status and extent of primary surgery (all p<0.1), but only pathologic nodal status continued to predict for LRC on MVA (p=0.03). While HPV status had no association with LRC on UVA (p=0.076), subgroup analysis showed a significant 1-year LRC benefit for HPV+ patients treated with CRT (HPV+ vs. HPV-: 100% vs. 50%, p=0.04). Patients with pN+ disease had a significantly lower 1-year LRC (47% vs. 89%, p=0.002). In subgroup analysis of pN+ patients (n=28), there was a LRC benefit on MVA associated with the addition of CRT (HR 0.23; 95% CI 0.06-0.84, p=0.03) and in HPV+ disease (HR 0.16; 95% CI 0.03-0.74, p=0.02). Pathologic nodal involvement predicts for worse LRC in penile cancer. In our retrospective series, CRT is associated with improved LRC with HPV + disease or with pathologic nodal involvement. Therefore, we recommend prospective investigation of the benefit of adjuvant CRT in these patients.