Original ArticlesHPV-related Sinonasal Carcinoma Clinicopathologic Features, Diagnostic Utility of p16 and Rb Immunohistochemistry, and EGFR Copy Number AlterationJiromaru, Rina MD*; Yamamoto, Hidetaka MD, PhD*; Yasumatsu, Ryuji MD, PhD†; Hongo, Takahiro MD*; Nozaki, Yui MD*; Hashimoto, Kazuki MD, PhD†; Taguchi, Kenichi MD, PhD‡; Masuda, Muneyuki MD, PhD§; Nakagawa, Takashi MD, PhD†; Oda, Yoshinao MD, PhD*Author Information Departments of *Anatomic Pathology †Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University Departments of ‡Pathology §Head and Neck Surgery, National Kyusyu Cancer Center, Fukuoka, Japan Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Yoshinao Oda, MD, PhD, Department of Anatomic Pathology and Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan (e-mail: [email protected]). The American Journal of Surgical Pathology: March 2020 - Volume 44 - Issue 3 - p 305-315 doi: 10.1097/PAS.0000000000001410 Buy SDC Metrics Abstract The prevalence and prognostic value of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) alteration in sinonasal squamous cell carcinoma (SNSCC) are not known. The reliability of p16 overexpression as a surrogate for HPV infection in SNSCC is also unclear. We investigated the prognostic and diagnostic significances of HPV infection, EGFR alteration, and p16 expression in SNSCC. We analyzed high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain (CNG) by chromogenic in situ hybridization and by determining the protein expressions of p16, Rb, and EGFR by immunohistochemistry in 101 SNSCC cases. HPV infection (n=9, 8.9%) and p16 overexpression (n=15, 14.9%) were associated with better overall survival (P=0.0042 and 0.005, respectively). The HPV+ cases were located predominantly at the nasal cavity with nonkeratinizing histology and partial loss of Rb. Notably, 40% (6/15) of p16+ SNSCCs were HPV−. Two of these cases showed complete loss of Rb expression by immunohistochemistry, suggesting a reason for the above discrepancy. EGFR CNG, detected in 30.5% of the SNSCCs, was correlated with EGFR protein overexpression (P=0.0001). HPV infection and EGFR CNG were mutually exclusive. The HPV+/EGFR CNG− group had significantly better overall survival than the HPV−/EGFR CNG− and HPV−/EGFR CNG+ groups (P=0.0471 and 0.0343, respectively). Our results suggest that HPV infection is a favorable prognostic marker in SNSCC, but p16 is not a perfect surrogate marker; the Rb expression pattern may improve the diagnostic accuracy. The molecular subclassification of SNSCCs based on HPV infection and EGFR copy number status might provide important information for therapeutic strategies. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.