(1) Background: Confocal laser endomicroscopy (CLE) has emerged as a transformative tool in head and neck surgery, with applications spanning oncologic insights and functional evaluations. This study delves into CLE’s potential in these domains. (2) Methods: We performed CLE in head and neck oncologic surgery, focusing on tumor margin identification and precise resection. We also employed CLE for functional assessment in allergic rhinitis, observing real-time mucosal changes during nasal provocation testing. (3) Results: In oncologic surgery, CLE enabled real-time visualization of tumor margins and cellular patterns, aiding resection decisions. In allergic rhinitis assessment, CLE captured dynamic morphological alterations upon allergen exposure, enhancing understanding of mucosal reactions. (4) Conclusions: The integration of CLE with evolving technologies such as deep learning and AI holds promise for enhanced diagnostic accuracy. This study underscores CLE’s expansive potential, highlighting its role in guiding surgical choices and illuminating inflammatory processes in the head and neck.

Introduction Probe-based confocal laser endomicroscopy (p-CLE) is a method for real-time in vivo visualization of mucosal changes on a cellular level. Due to the size of the endoscopes, it was mainly used in the gastrointestinal tract so far. First investigations on head and neck carcinoma described the oropharyngeal application. The further miniaturization of the laser probe now allows endonasal application and, thus, first experiences with the investigation of endonasal neoplasms. Objectives The aim of the present investigation is to elucidate, based on the morphological criteria validated in the oropharynx, whether these criteria be transferred in a similar way to the endonasal mucosa. Methods We conducted p-CLE (Cellvizio, Paris, France) with intravenous fluorescein staining in endoscopic sinus surgery in a patient with sinonasal inverted papilloma and a histologically confirmed squamous cell carcinoma. We compared the cellular visualization of pathological changes with those of healthy mucosa in the same specimen, and also with our former findings in the oropharynx. Results Endonasal p-CLE proved to be quite feasible in the surgical setting, and the transfer of malignancy criteria in analogy to histological examination could be optically retraced. Furthermore, additional criteria for tissue dignity assessment were obtained. Conclusion Our results suggest that endonasal application of p-CLE represents a valuable extension of the diagnostic repertoire available to date by an additional real-time analysis of the nasal mucosa. This is of particular value in surgically challenging anatomical areas such as the paranasal sinuses.Further investigation and validation will be necessary.

Zusammenfassung: Hintergrund Die konfokale Laserendomikroskopie (CLE) ist eine Methode zur In-vivo-Echtzeit-Visualisierung von Schleimhautveränderungen auf zellulärer Ebene. Erste Untersuchungen bei Kopf-Hals-Karzinomen beschrieben die oropharyngeale Anwendbarkeit. Ziel dieser Untersuchung ist es, anhand der im Oropharynx validierten Kriterien zu klären, ob diese auf die endonasalen Schleimhäute übertragen werden können. Methode Wir verwendeten die CLE mit intravenöser Fluorescein-Färbung vor und während der endoskopischen Operation bei einem Patienten mit einem sinunasalen invertierten Papillom sowie einem Patienten mit einem endonasalen Plattenepithelkarzinom. Wir verglichen die zelluläre Darstellung der pathologischen Veränderungen mit der der gesunden Schleimhaut der Gegenseite desselben Patienten sowie mit unseren früheren Befunden im Oropharynx. Ergebnisse Die endonasale CLE erwies sich als im operativen Setting gut durchführbar und die Übertragung von Malignitätskriterien in Analogie zur histologischen Untersuchung konnte optisch gut nachvollzogen werden. Darüber hinaus ergaben sich zusätzliche Kriterien zur geweblichen Dignitätsbeurteilung. Schlussfolgerung Unsere Ergebnisse legen nahe, dass die endonasale CLE eine wertvolle Erweiterung des diagnostischen Repertoires durch eine zusätzliche Echtzeitanalyse der Nasenschleimhaut darstellt. Dies ist von besonderem Wert in chirurgisch anspruchsvollen anatomischen Bereichen wie den Nasennebenhöhlen. Weitere Untersuchungen und eine Validierung dieser Ergebnisse werden notwendig sein, um die Sicherheit der Methode beurteilen zu können.

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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.