Abstract
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.
Highlights
Vulvar cancer represents less than 5% of all gynaecological malignancies, with an incidence of 2-3 per 100000 women per year in developed countries [1]
HPVDNA was detected in 29 corresponding pathological specimens; vulvar squamous cell carcinomas (VSCCs) were divided in Human Papillomavirus (HPV)-negative (27, 48.2%) and HPVpositive (29; 51.8%)
The other more frequent genotypes were HPV 52 and HPV 44, that were never related before to VSCC [4, 19]. This could be the result of changes of HPV genotypes distribution, consequent both to the introduction of new HPV genotypes, due to immigration, and different patterns of exposure, related to social and behavioural variables, as already shown by Dal Bello et al in Italian women affected by cervical intraepithelial neoplasia (CIN) [20]
Summary
Vulvar cancer represents less than 5% of all gynaecological malignancies, with an incidence of 2-3 per 100000 women per year in developed countries [1]. The carcinogenesis related to HPV-persistent infection accounts for 43-60% of vulvar squamous cell carcinomas (VSCCs) and is especially caused by high-risk (HR) HPV genotypes, in particular HPV 16, and HPV 18, 31, 33 and 45 [4]. These two kinds of VSCC are characterized by different clinic and histologic features. A better prognosis has been previously reported in HPV-positive oropharyngeal and anal cancers and has been related to an historically-documented better response to chemo- and radiotherapy [11-13] Nowadays, these evidences have not still been confirmed in HPV-related VSCCs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
