the-impact-of-HPV-infection-on-risk-of-progression-and-overall-mortality-in-vulvar-squamous-cell-carcinoma-a-retrospective-single-center-analysis_SR-JSO-2019-1-103

Aims: To investigate the impact of Human Papillomavirus (HPV) infection on clinic and histopathologic characteristics, and prognostic factors of patients affected by vulvar squamous cell carcinoma (VSCC). Methods: Fifty-six patients diagnosed with VSCC at the IRCCS Fondazione Policlinico San Matteo, Pavia, Italy, from March 2001 to February 2016, were enrolled in a retrospective analysis. HPV DNA was detected by the INNO-LiPA HPV genotyping assay, version EXTRA II, on corresponding pathological specimens. Clinic and histopathologic characteristics were compared through Fisher's exact test. Kaplan–Meier survival curves and Cox regression models were used to analyze prognostic factors. Results: According to the Kaplan–Meier curves, no differences were found neither in Disease Free Survival (DFS) (p=0.221), nor in Overall Survival (OS) (p=0.135) between HPV-positive and HPV-negative patients. At Cox multivariate analysis, lymph node metastasis and positive surgical margins were significantly associated to higher risk of progression/relapse. This association was retained but decreased by lymph node metastasis (HR=5.92, 95% CI: 2.16 – 16.23; p<0.001) and positive surgical margins (HR=3.10, 95% CI: 1.13 – 6.50; p=0.028) in case of HPV-positivity, that was instead related to lower risk of disease progression/relapse (HR=0.31, 95% CI: 0.13 – 0.75; p=0.009). Age ? 75 years, lymph node metastasis and adjuvant radiotherapy were statistically associated to higher mortality rate. A significant reducing effect on mortality was shown adjusting HPV for lymph node extracapsular spread (HR=0.38, 95% CI: 0.16-0.88; p=0.025), and FIGO stage > I (HR=0.42, 95% CI: 0.19 – 0.95; p=0.037), that, instead, related to higher risk of death for any cause (HR=4.46, 95% CI: 1.51 – 13.19; p=0.007 and HR=2.53, 95% CI: 1.12 – 5.73; p=0.026, respectively). Conclusions: Risk of progression is reduced in HPV-positive patients with node metastasis and positive surgical margins. Overall, HPV infection has a protective effect on mortality in case of node extracapsular spread or FIGO stage > I.