Supplementary Material for: Detection of Merkel Cell Polyomavirus in Epidermodysplasia-Verruciformis-Associated Skin Neoplasms

Background: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias. Objective: To examine whether EV is associated with cutaneous MCPyV infection. Methods: We used MCPyV-specific PCR to study skin neoplasms of 6 congenital EV patients and of 1 patient with acquired EV. Results: In all congenital EV patients, MCPyV DNA was found in carcinomas in situ, in invasive squamous cell carcinomas and in common warts. In 4 of these patients, the MCPyV-positive skin lesions were from different anatomic locations. In addition, 1 immunosuppressed patient suffering from acquired EV harbored MCPyV DNA in 2 common warts. In contrast, 7 normal skin samples tested negative for MCPyV DNA. Only 2 out of 24 carcinomas in situ (8.3%) and 2 out of 30 common warts (6.7%) from immunocompetent individuals were positive for MCPyV DNA. Conclusions: The strong association of EV-associated skin neoplasms with MCPyV suggests a unique susceptibility of EV patients to infections with MCPyV. Both MCPyV and EV-HPV may act as synergistic oncogenic cofactors in the development of EV-associated skin neoplasms.

背景：疣状表皮发育不良（Epidermodysplasia verruciformis, EV）是一种罕见的遗传性皮肤病，特征为对特定基因型人乳头瘤病毒（human papillomavirus, HPV）感染易感。在多瘤病毒家族中，新型默克尔细胞多瘤病毒（Merkel cell polyomavirus, MCPyV）已在多种上皮性皮肤肿瘤中被检出。目的：探讨疣状表皮发育不良是否与皮肤MCPyV感染存在关联。方法：采用MCPyV特异性聚合酶链反应（PCR），对6例先天性EV患者及1例获得性EV患者的皮肤肿瘤样本进行检测分析。结果：所有先天性EV患者的原位癌、浸润性鳞状细胞癌及普通疣样本中均检出MCPyV DNA。其中4例患者的MCPyV阳性皮损来自不同解剖部位。此外，1例罹患获得性EV的免疫抑制患者的2处普通疣中也检出了MCPyV DNA。与之相对，7份正常皮肤对照样本的MCPyV DNA检测结果均为阴性。在免疫功能正常个体的24份原位癌样本（占比8.3%）及30份普通疣样本（占比6.7%）中，仅各有2份样本呈MCPyV DNA阳性。结论：EV相关皮肤肿瘤与MCPyV的强相关性提示，EV患者对MCPyV感染具有独特易感性。MCPyV与EV相关HPV可能作为协同致癌辅助因子，共同参与EV相关皮肤肿瘤的发生发展过程。