Purpose/Objective(s): 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 in women who undergo surgery followed by adjuvant radiation therapy (RT).

Materials/Methods: A retrospective chart review was undertaken of all women treated with adjuvant radiation 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 diffuse, 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. Time to an event was defined as the time from completion of RT.

Results: Thirty nine women were identified. Median follow up was 25.6 months and 43.3 months for living patients. Ten women (25.6%) had p16+ pathology. The median age at diagnosis was 59.3 years for women with p16+ tumors and 70.2 years for women with p16- tumors (p=0.04). The distribution of stage did not differ by p16-status. The median maximal vulvar dose was 54.4Gy (range: 42.6-63.0Gy). The indication for adjuvant RT was close/positive margins in 19 women (48.7%), positive nodes in 8 (20.5%), and both in 12 (30.8%). The average pathologic tumor size was 2.1cm for p16+ tumors and 3.4cm for p16- tumors (p=0.028). Average margin size was not statistically different. There was a trend towards differences in the average number of pathologically involved lymph nodes, 0.5 vs 1.26 for p16+ vs p16-, p=0.077. Vulvar control rates differed by p16 status at 2 years: 88.9% vs 52.3% for p16+ vs p16-, p=0.041. This translated to a strong trend in differences in two-year locoregional control as well: 77.8% vs 47.4% for p16+ vs p16-, respectively, p=0.064. In women with only one indication for adjuvant RT, this benefit was more pronounced for women with p16+ tumors vs p16-: 2-year locoregional control 100% vs 48.5%, p=0.041. Two-year overall survival was not significantly different between p16+/- cohorts (88.9% vs 64.6%, p=0.405). Survival was impacted by risk factors necessitating adjuvant RT, however. Women with either close/positive margins or positive nodes had a 2-year survival of 80.4% vs 50.0% for women with both risk factors (p=0.044). p16+/- status did not statistically influence survival for women with one risk factor, but survival was numerically different at 2 years (100% vs 73.2%).

Conclusion: p16 positivity appears to be a prognostic factor for locoregional control rates in VSCC treated with vulvectomy and adjuvant radiation therapy for close/positive margins or positive lymph nodes. This benefit was pronounced especially in women with only close/positive margins or positive lymph nodes.