Discordance Between p16-Expression and HPV-Status in Sinonasal Carcinoma: A Multicenter Retrospective Study

Background/Objectives: Human papillomavirus (HPV) infection is a well-established risk factor for oropharyngeal squamous cell carcinoma (OPSCC), where p16 immunohistochemistry serves as a surrogate marker. However, the role of HPV in sinonasal squamous cell carcinoma (SNSCC) remains less defined, and the reliability of p16 as a standalone surrogate is under debate. This study aimed to assess the concordance between p16 expression and HPV-DNA status in SNSCC and characterize clinicopathologic features in HPV-associated cases. Methods: We retrospectively analyzed 111 SNSCC cases diagnosed between 2008 and 2024 at two German centers. p16 status was determined by immunohistochemistry using site-specific antibody protocols. HPV-DNA testing and genotyping were performed via PCR and reverse hybridization. Clinical and histopathological data were collected and compared between HPV-positive and -negative tumors. Results: HPV-DNA was detected in 31/111 cases (27.9%), with HPV16 and HPV33 (Site A) and HPV 16 and HPV18 (Site B) being the most frequent subtypes. Discordance between p16 and HPV-DNA status was observed in 29.7% of cases, with site-specific discordance rates of 44.6% and 14.5%. Patients with HPV-positive tumors were younger than their HPV-negative counterparts. Conclusions: Our findings underscore the limitations of p16 as a single surrogate marker for detecting HPV-associated sinonasal cancer. Future research on the role of HPV in sinonasal cancer should integrate complementary testing methods (like p16Ink4A immunohistochemistry and HPV DNA/mRNA analysis) and aim for test standardization.