Jiromaru R, et al. - The prognostic and diagnostic significances of human papillomavirus (HPV) infection, epidermal growth factor receptor (EGFR) alteration, and p16 expression in sinonasal squamous cell carcinoma (SNSCC) were examined. Researchers assessed 101 SNSCC cases for high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain by chromogenic in situ hybridization and the protein expressions of p16, Rb, and EGFR by immunohistochemistry. Overall survival was better in correlation with HPV infection (n = 9, 8.9%) and p16 overexpression (n = 15, 14.9%). Outcomes indicate the value of HPV infection as a favorable prognostic marker in SNSCC, however, p16 is not recognized as a perfect surrogate marker; the diagnostic accuracy may improve with assessing the Rb expression pattern. The molecular subclassification of SNSCCs on the basis of HPV infection and EGFR copy number status may yield valuable data for therapeutic strategies.