Prognostic impact of p16 and high-risk HPV DNA in ~1300 patients with vulvar cancer.

The study aimed to investigate whether vulvar squamous cell carcinoma (VSCC) survival varies by human papillomavirus (HPV) status measured by p16 expression and to determine whether high-risk HPV (hrHPV) DNA detection adds further prognostic information. Our cohort included 1277 women with histologically verified VSCC (1990-2017) categorized according to p16 and hrHPV DNA. Crude survival was estimated using Kaplan-Meier, and differences in restricted mean survival time were estimated in linear regression models. Analyses were stratified by p16 and p16/hrHPV status and stage, and adjustment included age, calendar year, and comorbidity. Overall analysis showed that 5-year survival was 67% (95% CI: 63-71%) and 45% (95% CI: 42-48%) in p16-positive and p16-negative VSCC, respectively. Overall, detection of hrHPV was associated with a 23% (95% CI: 6-40%) improvement in 5-year survival in p16-positive VSCC, whereas hrHPV status did not impact 5-year survival in p16-negative VSCC. In adjusted analysis, the survival difference by p16 status increased with increasing stage with a 26% (95% CI: 4-46%) higher 5-year survival in FIGO IV disease if the tumor was p16-positive compared to p16-negative, corresponding to a restricted mean survival time difference of 18 months in favor of p16 positivity. The largest VSCC cohort to date confirms the beneficial prognostic impact of p16 expression regardless of age and comorbidity and with the greatest impact in women with advanced disease. Classification according to p16 was adequate for p16-negative VSCC, whereas the survival of p16-positive VSCC was higher if hrHPV testing was also positive.