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Abstract: Objective: Recent evidence has confirmed two independent pathways in the development of vaginal squamous cell carcinoma (VaSCC): one related to and the other independent of human papillomavirus (HPV). The aim of our study was to evaluate whether HPV status has prognostic significance in this neoplasm. Methods: All confirmed primary VaSCCs diagnosed and treated from 1995 to 2009 in two institutions were retrospectively evaluated (n=57). HPV infection was detected by PCR using SPF-10 primers and typed with the INNO-LIPA HPV assay and p16INK4a expression by immunohistochemistry. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan–Meier analysis with the log-rank test and a multivariate Cox proportional hazard''s model. Results: HR-HPV DNA was detected in 70.2% patients. HPV16 was the most prevalent genotype (67.5% of cases). p16INK4a was positive in 97.5% HPV-positive and 17.6% HPV-negative tumors (p<.001). FIGO stage was associated with DFS (p=.042) and OS (p=.008). HPV-positive tumors showed better DFS (p=.042) and OS (p=.035) than HPV-negative tumors. Multivariate analysis confirmed better DFS and OS of HPV-positive patients independent of age and stage. This reduced risk of progression and mortality in HPV-positive patients was limited to women with FIGO stages I and II tumors (HR=0.26; 95% CI 0.10–0.69; p=0.006). Conclusions: HPV-positive early stage (FIGO I and II) VaSCCs have a better prognosis than early HPV-negative tumors. HPV detection and/or p16INK4a immunostaining can be easily implemented in routine pathology and should be considered as valuable prognostic biomarkers in the study of patients with VaSCC. [Copyright &y& Elsevier]

Abstract: Objective: Less than 5% of women with cervical or vaginal biopsy proven high-grade squamous intraepithelial lesions (HG-SIL) show a negative Hybrid Capture 2 (HC2) result. We analyzed 1) human papillomavirus (HPV) genotypes by PCR in order to determine whether these cases represent infections by common or unusual types, and 2) the clinical, colposcopic and pathological differential characteristics of these patients. Methods: 646 women with a histological diagnosis of HG-SIL and a HC2 test collected within 6months prior to the diagnosis were identified. Patients with a negative HC2 result were selected. HPV was typed in the biopsy specimen in all by PCR using SPF10 and GP5+/6+ primers, and p16INK4a immunostaining was performed. The clinical and colposcopy findings of these women were compared with a control group of HG-SIL with positive HC2 result. Results: 20 women (3.1%) with HG-SIL had a negative HC2. All biopsies were positive for p16INK4. PCR analysis detected HPV types included in HC2 test in 55% of the cases, with an identical percentage of common viruses between women with relative light unit values above or below 0.40 (p=.361). False negative HC2 tests increased with age (p=.002) and were more frequent in patients with non satisfactory colposcopy or small sized lesions (p<.001). Conclusion: A negative HC2 test is an infrequent event in women with HG-SIL. Common HPV types are identified in over half of the cases. Older women and patients with small lesions or non satisfactory colposcopy have a higher rate of HC2 negative results. [Copyright &y& Elsevier]

Abstract: Background: Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy. Methods: All VSCC diagnosed from 1995 to 2009 were retrospectively evaluated (n =98). HPV infection was detected by amplification of HPV DNA by PCR using SPF-10 primers and typed by the INNO-LIPA HPV research assay. p16INK4a expression was determined by immunohistochemistry. Disease-free and overall survival (DFS and OS) were estimated by Kaplan–Meier analysis with the log-rank test and a multivariate Cox proportional hazard''s model. Results: HR-HPV DNA was detected in 19.4% of patients. HPV16 was the most prevalent genotype (73.7% of cases). p16INK4a stained 100% HPV-positive and 1.3% HPV-negative tumors (p <.001). No differences were found between HPV-positive and -negative tumors in terms of either DFS (39.8% vs. 49.8% at 5years; p =.831), or OS (67.2% vs. 71.4% at 5years; p =.791). No differences in survival were observed between HPV-positive and -negative patients requiring radiotherapy (hazard ratio [HR] 1.04, 95% confidence interval [CI] .45 to 2.41). FIGO stages III–IV (p =.002), lymph node metastasis (p =.030), size≥20mm (p =.023), invasion depth (p =.020) and ulceration (p =.032) were associated with increased mortality but in multivariated only lymph node metastasis retained the association (HR 13.28, 95% CI 1.19 to 148.61). Conclusions: HPV-positive and -negative VSCCs have a similar prognosis. Radiotherapy does not increase survival in HPV-positive women. [Copyright &y& Elsevier]