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.

Background/Objectives: Building upon the rising value of Confocal Laser Endomicroscopy (CLE) in squamous cell carcinoma of the head and neck, we present the first application of CLE during the resection of sinonasal malignant melanomas. This study aims to evaluate the potential of CLE to assist surgeons in intraoperative decision-making, with a particular focus on resection margin assessment within the constrained nasal cavity. Methods: Two cases of sinonasal malignant melanoma were included in this study. CLE was employed to examine visible tumors and their margins, both pre- and post-endoscopic resection. The findings were compared to histopathological results as well as data on squamous cell carcinoma, for which malignancy criteria had already been established in prior projects. Results: CLE provided the real-time visualization of sinonasal malignant melanomas and their margins, successfully differentiating between healthy and neoplastic tissue compared to histopathological findings. Conclusion: CLE offers the potential for real-time assessment, aiding surgeons in more precise tumor resection and potentially improving patient outcomes. This study demonstrates the feasibility of using CLE in the resection of sinonasal malignant melanoma, highlighting its ability to differentiate between healthy and neoplastic tissue intraoperatively.

Background/Objectives: Sinonasal malignancies are rare and highly diverse cancers that pose significant diagnostic challenges due to their variable histological features and complex anatomical locations. Accurate diagnosis is critical for guiding treatment, yet conventional methods often require multiple biopsies. This study aimed to evaluate the potential of confocal laser endomicroscopy (CLE) for real-time imaging of sinonasal tumors to characterize specific features of different entities and improve diagnostic precision. Methods: Ten patients with various sinonasal malignancies, including squamous cell carcinoma, adenocarcinoma, sinonasal undifferentiated carcinoma, olfactory neuroblastoma, sinonasal mucosal melanoma, and endonasal lymphoma, were examined using CLE during diagnostic endoscopy. CLE images were compared descriptively with histopathological cross-sections to identify unique imaging patterns for each tumor type. Results: CLE was feasible across all cases, with high-quality images obtained despite anatomical challenges in some cases. Characteristic features, such as vascular clusters in undifferentiated carcinoma, mucin-filled bubbles in adenocarcinoma, and small round cells in neuroblastoma, were identified and corresponded well with histopathological findings. CLE also helped guide biopsies by revealing areas with diagnostic relevance. Conclusions: CLE demonstrates promise as an adjunct diagnostic tool in sinonasal malignancies, offering real-time imaging that correlates with histopathological findings and aids in targeted biopsies. While this study provides preliminary insights into the utility of CLE, further research with larger cohorts and statistical validation is necessary to establish its diagnostic reliability and broader clinical application.