Oncogenic Human Papillomaviruses Drive One-Third of Sinonasal Squamous Cell Carcinoma and Are Not Mutually Exclusive for Gene Mutations

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.