Abstract
BackgroundVulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract. We aimed to determine the mucosal high-risk human papillomavirus (HPV)-attributable fraction of VSCCs from Italian women using multiple markers of viral infections.MethodsVSCCs and 8 metastatic lymph node samples from 107 Italian women were analyzed by a highly type-specific multiplex genotyping assay for the presence of DNA from 119 different HPVs. Tissues were further analyzed for HPV RNA and for upregulation of the cellular protein p16INK4a.ResultsThe rate of mucosal HPV-related tumors defined by viral DNA and RNA positivity was low (7.8%). HPV16 was the most prevalent, followed by 53, 56, and 58. Only five (4.9%) p16INK4a-positive tumors were also positive for both viral DNA and RNA. One (14.3%) metastatic lymph node sample was positive for all three markers. DNA of cutaneous HPVs was detected in only two VSCCs, i.e. genus beta types 5 and 110.ConclusionA small proportion of Italian VSCCs is putatively HPV-related, i.e. positive for both viral DNA and RNA of the same type, thus reinforcing the importance of HPV vaccination. Moreover, this study suggests that a direct role of HPV from genus beta and gamma in vulvar carcinogenesis is unlikely.
Highlights
Vulvar squamous cell carcinoma (VSCC) is a rare tumor of the female genital tract, accounting for about 5% of all gynecological malignancies [1, 2]
Multiple human papillomavirus (HPV) infections were detected in two metastatic lymph node samples (MTS) cases; both were positive for HPV6 and HPV16 (Table 1)
Matched VSCC and MTS cases of three women were positive for the same HPV DNA, i.e. HPV6 (n = 2) and HPV16 (n = 1)
Summary
Vulvar squamous cell carcinoma (VSCC) is a rare tumor of the female genital tract, accounting for about 5% of all gynecological malignancies [1, 2]. Based on a pooled prevalence rate of HPV DNA, 34% of vulvar cancers have been reported to be attributable to HPV [15]. The use of additional markers for active HR-HPV infections, such as overexpression of the human cyclin-dependent kinase-4 inhibitor p16INK4a (p16) or/and detection of viral RNA, may enable more precise estimation of the proportion of VSCC that may be attributable to HPV, as previously shown in head and neck cancer [16]. Vulvar squamous cell carcinoma (VSCC) is a rare malignancy of the female genital tract. We aimed to determine the mucosal high-risk human papillomavirus (HPV)-attributable fraction of VSCCs from Italian women using multiple markers of viral infections
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