High-Risk Human Papillomavirus E6/E7 mRNA Is Rarely Detected in Nonanogenital Cutaneous Squamous Cell Carcinoma: An RNA In Situ Hybridization–Based Tissue Microarray Study. (March 2019)

• Record Type: Journal Article
• Authors: Fujimoto, Masakazu; Matsuzaki, Ibu; Takahashi, Yuichi; Iwahashi, Yoshifumi; Warigaya, Kenji; Kojima, Fumiyoshi; Jinnin, Masatoshi; Murata, Shin-ichi
• Is Part Of: American journal of dermatopathology. Volume 41:Number 3(2019)
• Publication Date: 2019-03
• Subjects: human papillomavirus -- E6/E7 mRNA in situ hybridization -- RNAscope -- cutaneous squamous cell carcinoma; Skin -- Diseases -- Periodicals; Histology, Pathological -- Periodicals; 616.50705
• DOI: 10.1097/DAD.0000000000001289
• Languages: English
• ISSNs: 0193-1091

Abstract

Abstract : Abstract: 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.