Background 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. Methods VSCCs 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 p16 INK4a . Results The 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%) p16 INK4a -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. Conclusion A 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.

中文翻译：

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人乳头瘤病毒感染在意大利女性外阴癌病因中的作用

背景外阴鳞状细胞癌（VSCC）是一种罕见的女性生殖道恶性肿瘤。我们旨在使用多种病毒感染标志物确定意大利女性 VSCC 的黏膜高危人乳头瘤病毒 (HPV) 归因部分。方法通过高度类型特异性的多重基因分型分析对来自 107 名意大利女性的 VSCC 和 8 个转移性淋巴结样本进行分析，以确定来自 119 种不同 HPV 的 DNA 的存在。进一步分析组织的 HPV RNA 和细胞蛋白 p16 INK4a 的上调。结果以病毒DNA和RNA阳性定义的黏膜HPV相关肿瘤发生率较低（7.8%）。HPV16 是最普遍的，其次是 53、56 和 58。只有五个 (4.9%) p16 INK4a 阳性肿瘤对病毒 DNA 和 RNA 也呈阳性。一个（14。3%) 转移性淋巴结样本对所有三个标志物均呈阳性。仅在两种 VSCC 中检测到皮肤 HPV 的 DNA，即 5 型和 110 型。结论 一小部分意大利 VSCC 被推定与 HPV 相关，即同一类型的病毒 DNA 和 RNA 均呈阳性，因此加强了HPV疫苗接种。此外，这项研究表明，来自 β 和 γ 的 HPV 在外阴癌发生中的直接作用不太可能。