Department of Dermatology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA; Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA.
J Invest Dermatol. 2022 May;142(5):1280-1290.e7. doi: 10.1016/j.jid.2021.10.009. Epub 2021 Oct 28.
Vulvar squamous cell carcinoma pathogenesis is traditionally defined by the presence or absence of human papillomavirus (HPV), but the definition of these groups and their molecular characteristics remain ambiguous across studies. In this study, we present a retrospective cohort analysis of 36 patients with invasive vulvar squamous cell carcinoma where HPV status was determined using RNA in situ hybridization and PCR. Clinical annotation, p16 immunohistochemistry, PD-L1 immunohistochemistry, HPV16 circular E7 RNA detection, and RNA sequencing of the cases were performed. A combination of in situ hybridization and PCR identified 20 cases (55.6%) as HPV positive. HPV status did not impact overall survival (hazard ratio: 1.36, 95% confidence interval = 0.307-6.037, P = 0.6857) or progression-free survival (hazard ratio: 1.12, 95% confidence interval = 0.388-3.22, P = 0.8367), and no significant clinical differences were found between the groups. PD-L1 expression did not correlate with HPV status, but increased expression of PD-L1 correlated with worse overall survival. Transcriptomic analyses (n = 23) revealed distinct groups, defined by HPV status, with multiple differentially expressed genes previously implicated in HPV-induced cancers. HPV-positive tumors showed higher global expression of endogenous circular RNAs, including several circular RNAs that have previously been implicated in the pathogenesis of other cancers.
外阴鳞状细胞癌的发病机制传统上由人乳头瘤病毒 (HPV) 的存在与否定义，但这些组的定义及其分子特征在不同的研究中仍然存在模糊性。在这项研究中，我们对 36 例浸润性外阴鳞状细胞癌患者进行了回顾性队列分析，使用 RNA 原位杂交和 PCR 确定 HPV 状态。对病例进行了临床注释、p16 免疫组化、PD-L1 免疫组化、HPV16 环状 E7 RNA 检测和 RNA 测序。原位杂交和 PCR 的组合将 20 例（55.6%）确定为 HPV 阳性。HPV 状态并未影响总生存（危险比：1.36，95%置信区间=0.307-6.037，P=0.6857）或无进展生存（危险比：1.12，95%置信区间=0.388-3.22，P=0.8367），并且两组之间未发现明显的临床差异。PD-L1 表达与 HPV 状态无关，但 PD-L1 表达增加与总生存较差相关。转录组分析（n=23）揭示了具有不同 HPV 状态的不同组，具有多个先前与 HPV 诱导的癌症相关的差异表达基因。HPV 阳性肿瘤表现出更高的内源性环状 RNA 的总体表达，包括以前被认为与其他癌症发病机制相关的几个环状 RNA。
