Prognostic Significance of Human Papilloma Virus and p16 Expression in Patients with Vulvar Squamous Cell Carcinoma...

Human papilloma virus (HPV) has been identified as an aetiological agent in a subset of patients with vulvar squamous cell carcinoma (VSCC). The prognostic role of HPV status in VSCC patients treated with radiotherapy has not yet been determined. We investigated the associations between HPV, p16 and clinical outcome in these women.

Patients undergoing potentially curative radiation treatment for VSCC at a single institution from 2000 to 2009 were retrospectively identified. Those who received definitive or peri-operative radiotherapy as part of treatment, and who had available pathological specimens, were included for analysis. HPV infection was detected using Roche Linear array hybridisation and p16 by immunohistochemistry. The locoregional relapse (LRR) rate was estimated using a cumulative incidence function to account for competing risks. Disease-free survival (DFS) and overall survival were analysed using the Kaplan-Meier method. The median follow-up was 4.9 years.

Forty patients were suitable for analysis, with a median age of 69.5 years. HPV was detected in 14/40 (35%) patients, HPV16 being the most common serotype (79%). Patients with HPV-positive tumours had lower 5 year LRR compared with those with HPV-negative tumours (14.3% versus 79.3%, Gray test P = 0.003). Tumour p16 positivity was also associated with lower 5 year LRR (15.4% versus 81.2%, Gray test P = 0.002). Patients with p16-positive tumours had higher 5 year DFS compared with those with p16-negative tumours (62% versus 7%, Log-rank test P = 0.02).

We have identified a favourable prognostic group in VSCC, with p16-positive patients showing improved outcomes. p16 has the potential to be a predictive marker allowing the identification of women more likely to have a favourable response to radiotherapy.