Chemoradiation Therapy for Vulvar Squamous Cell Carcinoma: Does p16-Positivity Predict for Better Response Rates and Outcomes?

Abstract

Vulvar squamous cell carcinoma (VSCC) is a relatively rare malignancy. Human papillomavirus (HPV) has been implicated as a causative factor for a subset of these patients. The purpose of this study is to evaluate if p16-positivity, which is surrogate for HPV infection, predicts for better response rates and survival. A retrospective chart review was undertaken of all women treated with neoadjuvant or definitive chemoradiation (CRT) therapy from 2000-2016 for VSCC at our institution. Available tissue blocks were stained for p16. Each tumor was assigned an H-score according to the College of American Pathologists criteria. P16-positivity was defined as strong immunoreactivity within invasive tumor with an H-score of 200+. P16 +/- groups were compared using Chi-squared and t-test. These were correlated with outcomes via Kaplan-Meier with log-rank technique. Factors which predicted for disease outcomes and overall survival were analyzed via Cox proportional hazards methods. Time to an event was defined as the time from completion of CRT or surgery following CRT if treated neoadjuvantly. A total of 74 women were identified who had follow-up and specimen available for staining. Median follow up was 14.1 months for all patients (range: 0.4-166.7 months) and 40.6 months for living patients. Thirty two (42.7%) women had p16+ tumors. Median age was 71.5 years (range: 37-91); for women with p16+ tumors, the average age was 67.8 years vs 70.0 years for women with p16- tumors (p=NS). The distribution of stage between p16-status did not differ. The median maximal vulvar dose was 50.4Gy (range: 33.6-70.2Gy). The complete clinical response (cCR) rate for p16+ tumors was 68.0% vs 34.2% for p16- tumors (p=0.009). The pathologic complete response (pCR) rate for women treated neoadjuvantly was 56.5% vs 29.7% for p16+ vs p16-, respectively (p=0.037). The combined clinical or pathologic complete response (CR) rate was 63% for p16+ and 27.5% for p16- (p=0.004). Two-year vulvar control for women with p16+ tumors was 77.8% vs. 45% for p16- (p=0.010). In women with p16+ tumors who achieved clinical or pathologic complete response, 2-year vulvar control was 90.9% vs 66.7% if p16- and CR (p=0.071). If complete response was not achieved, 2-year control rates were 55.6% vs. 34.9% (p=0.230). No woman with a p16+ tumor developed distant metastases vs. 7 with p16- tumor (p=0.013). OS was not statistically different between p16+/- complete responders (67.3% vs. 71.6%, p=0.719) but non-responders with p16+ tumors had higher 2-year OS compared with p16- tumors (70.0% vs. 22.6%, p=0.161). This is first study evaluating response to chemoradiation therapy for VSCC based on p16 positivity. P16-positive tumors appear to have better clinical and pathologic response rates and clinical outcomes. Future clinical trials may need to focus on different treatment strategy for p16-negative tumors as they seem to have a worse outcome with lower response rates and higher risk of distant metastases.