Abstract
Background. The detection rate of oncogenic human papillomaviruses (HPVs) in sinonasal squamous cell carcinomas (SNSCCs) varies among studies. The mutational landscape of SNSCCs remains poorly investigated. Methods. We investigated the prevalence and prognostic significance of HPV infections based on p16 protein expression, HPV‐DNA detection, and E6/E7 mRNA expression using immunohistochemistry, polymerase chain reaction, and in situ hybridization, respectively. In addition, we evaluated the genetic mutations in 59 patients using next‐generation sequencing. Results. One‐third of the SNSCCs were truly oncogenic HPV‐driven tumors associated with a nonkeratinizing morphology ( p = 0.01) and did not correlate with the prognosis. The following gene mutations were detected: TP53 , PIK3CA , CDKN2A , EGFR , and FGFR3 . These mutations occurred alone, in association with, or with oncogenic HPV. Conclusion. One‐third of SNSCCs were high‐risk HPV driven lesions. However, gene mutations and HR‐HPV infections are not mutually exclusive. Further studies are required to analyze the prognostic value of these associations.