Fujimoto Masakazu, Matsuzaki Ibu, Takahashi Yuichi, Iwahashi Yoshifumi, Warigaya Kenji, Kojima Fumiyoshi, Jinnin Masatoshi, Murata Shin-Ichi
Departments of Diagnostic Pathology, and.
Dermatology, Wakayama Medical University, Wakayama, Japan.
Am J Dermatopathol. 2019 Mar;41(3):205-210. doi: 10.1097/DAD.0000000000001289.
High-risk human papillomavirus (HR-HPV) is known to play an oncogenic role in squamous cell carcinoma (SCC) at certain anatomical sites, namely the uterine cervix, oropharynx, and anogenital skin. However, the association between HR-HPV and nonanogenital cutaneous SCC (CSCC) remains controversial. In this study, we addressed this controversy by performing HR-HPV E6/E7 mRNA in situ hybridization (ISH) on 243 CSCC samples. A cocktail of E6/E7 mRNA ISH probes, recognizing 18 HR-HPV genotypes, was applied to a tissue microarray of paraffin-embedded sections of 154 invasive and 89 in situ CSCC specimens. The anatomical sites of CSCC included the head and neck (n = 100), extremities (n = 100), trunk (n = 25), and anogenitalia (n = 18). We also investigated the correlation between the p16 expression and HR-HPV status by immunohistochemistry. The results of HR-HPV E6/E7 mRNA ISH showed that 5.8% (14/243) of all CSCC samples were positive for HR-HPV, including 66.7% (12/18) of the anogenital and only 0.9% (2/225) of the nonanogenital CSCC samples (P < 0.01). For the detection of diffuse p16 expression by immunohistochemistry, the sensitivity was 100% (14/14 HR-HPV-positive CSCC samples), and the specificity was 72.1% (165/229 HR-HPV-negative specimens). Thus, HR-HPV E6/E7 mRNA was rarely detected in nonanogenital CSCC, making it unlikely that the virus contributes to the pathogenesis of this malignancy. In addition, p16 immunoreactivity has a limited value as a surrogate marker for transcriptionally active HR-HPV in nonanogenital CSCC.
已知高危型人乳头瘤病毒（HR-HPV）在某些解剖部位的鳞状细胞癌（SCC）中发挥致癌作用，这些部位即子宫颈、口咽和肛门生殖器皮肤。然而，HR-HPV与非肛门生殖器皮肤鳞状细胞癌（CSCC）之间的关联仍存在争议。在本研究中，我们通过对243例CSCC样本进行HR-HPV E6/E7 mRNA原位杂交（ISH）来解决这一争议。将识别18种HR-HPV基因型的E6/E7 mRNA ISH探针混合物应用于154例浸润性和89例原位CSCC标本的石蜡包埋切片组织微阵列。CSCC的解剖部位包括头颈部（n = 100）、四肢（n = 100）、躯干（n = 25）和肛门生殖器（n = 18）。我们还通过免疫组织化学研究了p16表达与HR-HPV状态之间的相关性。HR-HPV E6/E7 mRNA ISH结果显示，所有CSCC样本中有5.8%（14/243）为HR-HPV阳性，其中肛门生殖器样本为66.7%（12/18），而非肛门生殖器CSCC样本仅为0.9%（2/225）（P < 0.01）。对于通过免疫组织化学检测弥漫性p16表达，敏感性为100%（14/14例HR-HPV阳性CSCC样本），特异性为72.1%（165/229例HR-HPV阴性标本）。因此，在非肛门生殖器CSCC中很少检测到HR-HPV E6/E7 mRNA，这使得该病毒不太可能参与这种恶性肿瘤的发病机制。此外，在非肛门生殖器CSCC中，p16免疫反应性作为转录活跃的HR-HPV替代标志物的价值有限。
