Introduction: Subgroups with a poorer prognosis exist among patients with human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). This study aims to identify histological and genetic differences within HPV-positive OPSCC and correlate these findings with patient outcomes. Methods: The study included 102 OPSCC patients, all tested positive for high-risk HPV DNA and p16INK4a expression. Based on histomorphological classification (HPV Prediction Classification, HPV PC), all cases were categorized as either classic HPV-positive OPSCC (cHPV) or non-classic HPV-positive OPSCC (non-cHPV). Nextgeneration sequencing (NGS) of selected genes was performed on 55 tumor samples, correlating results with morphological status and survival. Results: Of all cases, 49 % (n = 50/102) were categorized as non-cHPV, histomorphologically resembling HPVnegative OPSCC, and showed significantly poorer overall survival (p = 0.004) and five-year survival rate (5YS: 83.9 % vs. 58.4 %). Multivariate analyses identified HPV PC as an independent prognostic marker (p = 0.027). NGS revealed loss-of-Function (LOF) mutations in TP53 in three non-cHPV samples. Additionally, PIK3CA/PTEN mutations were found in 35.7 % (10/28) of non-cHPV cases. The cumulative burden of gene mutations was higher in the non-cHPV subgroup compared to the cHPV subgroup (n = 53, p = 0.1). Conclusion: HPV PC distinguished two histomorphological subgroups within HPV-positive OPSCCs: cHPV with excellent prognosis and non-cHPV with poorer overall survival. Non-cHPV tumors also exhibited higher overall mutation rates, notably LOF-TP53 and PIK3CA/PTEN mutations. These morphological subtypes, along with their corresponding mutational profiles, warrant further investigation as potential biomarkers for de-escalation intervention trials.

Abstract Introduction Locoregional recurrence (LR) is common in locally advanced head and neck cancer (HNSCC), posing challenges for treatment. We analysed outcome parameters and toxicities for patients being treated with radiotherapy (RT) for LR-HNSCC and investigated patient and disease related prognostic factors in this prognostically unfavourable group. Methods This analysis includes 101 LR-HNSCC patients treated with RT, radio-chemotherapy (RCT) or radio-immunotherapy (RIT) between 2010 and 2018 at a high-volume tertiary centre. Patient characteristics, tumour and treatment details were retrospectively collected. Overall survival (OS), progression-free survival (PFS) and toxicities according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 were assessed. Results 62% of patients were radiotherapy-naïve (initial RT group) while 38% were re-irradiated at site of LR (re-RT group). Median OS for initial RT was 24 months, for re-RT 12 months (p < 0.01). In the RCT subgroup, patients with initial RT had significantly longer OS with 35 months compared to re-RT 12 months (p < 0.05). Patients with UICC grade IV tumours and percutaneous endoscopic gastrostomy (PEG) tube had significantly shorter OS in multivariate analysis: initial RT 13 vs. re-RT 32 months and initial RT 12 vs. re-RT 32 months respectively. Salvage surgery before RT at recurrence was a positive prognostic factor for OS (initial RT 35 vs. re-RT 12 months). Other significant factors for longer OS in univariate analysis included low inflammatory status (Glasgow Prognostic Score 0) and radiation doses ≥ 50 Gy. We detected 37 (15%) ≥ CTCAE Grade 3 events for initial RT and 19 (15%) for re-RT patients. Conclusion In this analysis, we identified key prognostic factors including PEG tube and inflammation status that could guide treatment decision. Our findings suggest salvage surgery as preferred treatment option with postoperative RT at LR. Adverse events due to re-RT were acceptable. A radiation dose of ≥ 50 Gy should be administered to achieve better outcomes.

This retrospective study examined overall survival (OS), recurrence free survival (RFS), and laryngeal preservation time in a large cohort of 663 patients with T1/2 N0 M0 glottic cancer after transoral laser or open surgery vs radiotherapy. A total of 595 surgically treated patients and 68 individuals after definitive radio(chemo)therapy (R (C)–T) were studied. Patient characteristics including sociological, surgical, and pathological data, OS and RFS as well as laryngeal preservation time were recorded and compared between various groups/cohorts. There were no significant differences in OS and RFS between surgically treated and conservatively treated patients. However, laryngeal preservation time was significantly higher in surgically treated patients (p < 0.001) (mean: 138.3 ± 2.2 months, versus 102.8 ± 7.6 months) than those under conservative treatment. The surgical treatment method (transoral vs. open partial resection) did not influence OS or RFS. Additionally, the rate of transoral vs. open surgery did not change over a decade. T2-stage patients showed significantly lower RFS than T1-stage patients. Initial R status significantly influenced OS and tumor recurrence. The findings of this study exhibited a significantly longer laryngeal preservation time in patients with T1/2 N0 M0 glottic cancer treated surgically than in those treated with radiotherapy. No significant differences in OS or RFS were observed between open partial laryngectomy and transoral laser surgery. The R status had a significant impact on OS and RFS, with OS being significantly associated with an R0 status, regardless of T status or the surgical approach (open versus transoral). Laryngeal preservation surgery is recommended as a central therapeutic strategy for T1/2 N0 M0 glottic cancer because it has a higher laryngeal preservation rate than the conservative treatment. Given the high recurrence rate (18.5

Men who have sex with men (MSM) have a high risk of human papillomavirus (HPV) infection and HPV-related diseases. While gender neutral HPV vaccination between the ages of 9–14 years (with the option for catch-up between 15- and 17-years-of-age) has been recommended in Germany since 2018, adult MSM are currently not included and thus do not benefit from its advantages. This analysis aims to quantify the reduction in public health and health economic burden of including 18–26-year-old or 18–45-year-old MSM in the national HPV vaccination recommendation, compared to the status quo of vaccinating adolescent boys only. We developed a dynamic transmission model of HPV, with an integrated HIV model, to analyze the potential impact of the 9-valent HPV vaccination on HPV infections and HPV-related diseases (anal, penile, and oropharyngeal cancers, and anogenital warts). By including economic outcomes, the model provides estimates of the cost-effectiveness of HPV vaccination among adult MSM in Germany. Vaccinating MSM aged 18–26 years could prevent an additional 2,583 anal, penile and oropharyngeal cancers, 709 deaths and 81,372 anogenital warts. Expanding vaccination to MSM aged 18–45 years, 4,091 cancers, 1,516 deaths and 114,117 anogenital warts could be averted. The highest reductions were found in anal cancers and anogenital warts; significant incidence reductions in cancers were seen within about 20 years. Vaccinating 18–26 and 18-45-year-old MSM resulted in Incremental Cost-Effectiveness Ratios (ICERs) of 35,300.09€/QALY and 42,088.06€/QALY, respectively, when compared to the vaccination of adolescent boys only. Vaccination of MSM up to 26 and 45 years of age can profoundly accelerate beneficial public health outcomes while reducing the economic burden of HPV-related cancers and anogenital warts in a cost-effective way compared to vaccinating adolescent boys only.

Background: Salivary gland carcinomas (SGC) are rare head and neck malignancies with diverse molecular profiles and treatment challenges. Tissue factor (TF), a transmembrane glycoprotein involved in cancer pathophysiology, has emerged as a potential therapeutic target. Objectives: The objective of this study was to investigate TF expression in SGC and its correlation with clinicopathological data. Design: A cohort of 109 SGC patients who underwent curative surgery between 1990 and 2023 was analyzed. Methods: TF expression in primaries and lymph node (LN) metastases was assessed using immunohistochemistry on tissue microarrays. Histo-scores were calculated for cytoplasmic and membranous staining and correlated with clinicopathological data. Results: TF was expressed in 80.7% of samples with a mean combined H -score of 29.6. Moderate and high expression was found in 22.9% of all cases. Mucoepidermoid carcinoma (MEC), secretory carcinoma, and salivary duct carcinoma (SDC) showed the highest expression. A significantly higher membranous TF expression was observed in SDC LN metastases compared to primaries (71.1 vs 31.7, p = 0.012). Survival analysis revealed a trend toward worse outcomes for tumors with higher TF expression. Conclusion: This study provides the first analysis of TF expression in SGC revealing its presence across various subtypes. The findings suggest potential for TF-targeted therapies in SGC treatment, particularly for metastatic SDC and MEC. The trend toward worse survival outcomes in high TF-expressing tumors warrants further investigation.

Dear Editor, OPSCC has one of the most rapidly increasing incidences of all cancers.1-3 Most cases are associated with HPV infection, which confers improved survival outcomes, compared to HPV-independent disease.4 Despite advancements in understanding HPV-associated OPSCC, the role of biomarkers like B7-H3 and CEA, in both HPV-positive and HPV-negative cases remains unclear. This study addresses this gap by evaluating their expression and correlations with clinical and immune parameters. Additionally, we developed a quantitative Digital Image Analysis (DIA) workflow (Supplemental Methods) to assess its feasibility as a companion diagnostic tool for emerging B7-H3-targeted therapies. We observed widespread B7-H3 expression in OPSCC, while CEA expression was more limited. B7-H3 is a type I transmembrane protein of the Ig superfamily, which modulates T-cell activation through receptor binding.5 It is overexpressed in cervical cancer (HPV-driven disease) and Head and Neck Squamous Cell Carcinoma (HNSCC), where it correlates with poor prognosis.6, 7 We further observed a link between B7-H3 and CD8+ T-cell infiltration, which is promising for B7-H3-targeted therapies. CEA, an oncofetal protein, is widely used in colorectal cancer but less studied in head and neck cancer. Its established clinical role and widespread use in colorectal cancer support its inclusion in this study for potential clinical translation to OPSCC.8 This study included 545 OPSCC cases, with local ethical approval obtained for each institution (Supplemental Methods). The cohort was predominantly male (85.1%) with a mean age of 58.7 years (36–88) (Table 1). Semi-quantitative assessments and DIA-based H-scores were performed to quantify B7-H3 expression, which was then correlated with clinical outcomes and immune markers. Despite weak staining in most cases, 78.4% exhibited positive B7-H3 tumoural expression, while 71.0% showed positive stromal expression based on semi-quantitative assessment, highlighting its widespread prevalence in OPSCC. Given B7-H3's widespread expression in the initial 291 cases, a custom DIA workflow was developed. On these same initial cases, the median tumoural and stromal digital H-scores were 78.5 (IQR: 27.6–134.6) and 47.4 (IQR: 19.6–81.1), respectively. The semi-quantitative and H-scores correlated well for both tumoural and stromal expression (H(3)Tumour = 151.2, p < .001; H(3)Stroma = 36.5, p < .001; Figure 1). The results were similar when considering HPV-negative cases only, with strong correlations observed between semi-quantitative and H-scores (H(3)Tumour = 119.5, p < .001; H(3)Stroma = 30.0, p < .001) and a similar pattern of expression as presented above, with median tumoural and stromal H-scores of 80.3 (IQR: 18.5–157.9) and 54.0 (IQR: 15.0–103.6), respectively. This pipeline was then validated on 235 cases; the median tumoural and stromal H-scores were 42.8 (IQR: 13.5–109.8) and 31.4 (IQR: 13.0–65.8), respectively. Associations with clinical factors and prognostic value were evaluated on the overall cohort (N = 526). Neither tumoural nor stromal B7-H3 H-scores were significantly prognostic (HRTumour = 1.00, 95% CI: 1.00–1.00, p = .329; HRStroma = 1.00, 95% CI: 1.00-1.00, p = .556). On univariable analysis, tumoural and stromal B7-H3 H-scores significantly correlated with gender, smoking and alcohol history, T-stage, grade, and HPV-status (Table S3). When evaluating HPV-independent cases only, any alcohol history, M0-stage and lower tumour grade (i.e., more well-differentiated tumours) were each associated with higher B7-H3 tumour expression. Higher stromal B7-H3 scores were also observed with lower tumour grade (Table S4). Lastly, in the subgroup, which was evaluated for immune marker expression, B7-H3 expression did not significantly correlate with tumoural PDL1 nor PD1 expression. However, reduced CD8+ T-cell infiltration (p = .008) was associated with a higher B7-H3 tumoural H-score (Table 2). This significance remained when evaluating HPV-negative cases only (Table 3). Two hundred eighty-five cases were evaluated semi-quantitatively for CEA expression as a comparator biomarker (Figure S4), 68.8% of which were negative by IHC evaluation. 49.6% of cases demonstrated positive expression of CEA in tumour cells. Several cut-off values (1%, 5%, 10% and 50%) were explored to evaluate associations between CEA across the tissue section and other clinical factors (i.e., gender, T-stage, N-stage, M-stage, smoking/alcohol history, HPV status and overall survival). No significant correlations were observed except between CEA expression and HPV-status, which were significantly associated at all cut-off values, as well as between CEA expression and gender at the 50% cut-off value (Table S5). On univariable analysis, CEA at each cut-off was significantly predictive of overall survival, with positive expression correlating with superior survival. However, this significance was lost after adjusting for HPV status (Table S6). In cases for which data were available, CEA did not significantly correlate with any of PD-1, PDL1, CD8+ T-cell infiltration nor FoxP3 expression (Tables S7 and S8). Here, we present clinical findings from a large multi-centre OPSCC cohort, confirming known prognostic factors. Our DIA workflow enabled high-throughput B7-H3 analysis, demonstrating its utility as a companion diagnostic tool given its widespread expression. Notably, HPV-associated T4 and HPV-independent T1 cases had similar outcomes, underscoring the aggressiveness of early-stage HPV-independent disease and the need for improved therapies, such as those targeting B7-H3. However, high intratumour heterogeneity in HPV-independent OPSCC remains a key challenge in developing effective treatments. Interestingly, B7-H3 correlated with CD8+ T-cell presence and HPV status, with higher B7-H3 linked to reduced CD8+ infiltration, even in HPV-independent cases. CEA was present in a subset of cases, warranting further validation as a therapeutic target in head and neck cancer. In addition, we observed a more inflamed tumour microenvironment with greater T-cell infiltration for HPV-associated disease, compared to HPV-negative disease, consistent with previous research.9 Our findings suggest B7-H3 plays an immunosuppressive role in OPSCC, which has been shown in a separate study of HNSCC, where the authors further demonstrated an association between B7-H3 expression and poorer prognosis, highlighting the need for innovative immunotherapies.10 Further research should examine B7-H3's relationship with key OPSCC biomarkers, including PD-L1, p16, EGFR, and TP53, which have diagnostic and prognostic significance.1, 4 In conclusion, B7-H3 plays a key role in both HPV-associated and HPV-independent OPSCC and we have demonstrated the feasibility of digital IHC assessment as a potential companion diagnostic tool. Further research is needed to clarify underlying mechanisms and advance immunotherapeutic strategies for OPSCC. JL, HBC, SP, OE, NC, SJS, ML, JPK, JAT, MH conducted the data analysis, involved in study design and conception, manuscript preparation and editing. VS, OS, UW, NW, RCM, JD, DP, DA, NG, JL, ARA, DJH, LM, FMV, POF, CTF, LW, UR, JAH, JH, HR, AJ, TRF, MDF, OA, KC, JM, AS, MRJ, JPR, prepared and reviewed the final manuscript. The authors have nothing to report. The authors declare no conflicts of interest. The authors received no specific funding for this work. Local ethical approval was obtained from each institution: UCL/UCLH (UCL/UCLH Ethics Committee, 04/0099), HUCA (Ethical Committee of HUCA, 141/19), UHG (Ethics Committee of Giessen, AZ 95/15) and MUI (AN2014-0241, 340/4.2); multi-institutional analysis was performed in line with multicenter ethics obtained from UCL (UCL REC no. 9609/002). Data can be provided upon reasonable request by contacting the corresponding author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Background The histone gene H2AX and its phosphorylated protein γ-H2AX play a crucial role in the DNA damage response. This study investigates the expression of H2AX mRNA and its phosphorylated γ-H2AX protein in oropharyngeal squamous cell carcinoma (OPSCC), its association with distinct biological pathway alterations and its potential as a biomarker. Materials and Methods Expression of H2AX mRNA in 76 OPSCC from The Cancer Genome Atlas (TCGA) cohort was analyzed. Patients were stratified into H2AXhigh- and H2AXlow OPSCC based on a survival-associated cutoff. Differentially expressed genes were identified using DESeq2, followed by pathway enrichment analyses. Immunohistochemical staining of γ-H2AX protein expression was performed on an independent cohort of 209 OPSCC, followed by survival and Cox regression analyses. Results High H2AX mRNA expression was a significant prognostic factor associated with shorter OS in the TCGA OPSCC cohort (HR 4.77, p = 0.04). In H2AXhigh tumors, differential gene expression analysis revealed upregulation of genes regulating DNA repair and cell cycle (CDK1, CCNB1, ZWINT). High γ-H2AX protein expression was significantly associated with HPV-negative OPSCC (p = 0.005), and remained an independent predictor of poor survival in the total OPSCC cohort (HR 2.24, p = 0.03) and particularly in HPV-negative patients (HR 3.67, p = 0.007). Conclusion H2AX/γ-H2AX expression is a potential prognostic biomarker in OPSCC, with elevated levels indicating poor survival, especially in HPV-negative cases. These findings suggest distinct molecular behaviors in OPSCC based on H2AX expression and highlight the need for further investigation into its therapeutic implications.

Background:Patients with inoperable or metastatic oropharyngeal squamous cell carcinoma (OSCC) face limited therapeutic options. Nectin-4, an immunoglobulin-like transmembrane adhesion protein, and Trophoblast Surface Antigen 2 (TROP2), a transmembrane glycoprotein, have recently emerged as targets for antibody-drug conjugates (ADCs). Enfortumab Vedotin, an ADC targeting Nectin-4, has been approved for locally advanced or metastatic urothelial carcinoma, while sacituzumab govitecan, targeting TROP2, was approved for metastatic triple-negative breast cancer. Objectives:This study aimed to demonstrate expression rates of TROP2 and Nectin-4 in a representative cohort of human papillomavirus (HPV)-positive and HPV-negative OSCC and discuss the relevance of those markers as possible targets for ADCs. Design:A retrospective cohort study. Methods:We analyzed tissue samples from 226 OSCC patients treated at the University Hospital of Cologne between 2005 and 2020. The expression of Nectin-4 and TROP2 was assessed using immunohistochemistry, and the H-score method was applied to categorize expression levels into four groups: negative (0-10), low (11-100), moderate (101-200), and high (201-300). Results:TROP2 expression was positive in 96.5% of the samples, with 84.1% showing moderate to high expression (H-Score 101-300). A total of 38.8% of the cases expressed Nectin-4. Notably, patients with HPV-positive OSCC demonstrated significantly higher Nectin-4 expression compared to those with HPV-negative OSCC (p < 0.001). Conclusion:This study is one of the first to investigate the expression of Nectin-4 and TROP2 in a cohort of both HPV-positive and HPV-negative OSCC patients. Our results indicate that TROP2 is almost universally expressed in OSCC, while Nectin-4 expression is less frequent. TROP2 and Nectin-4 are promising therapeutic targets for OSCC, with Nectin-4 being particularly relevant for HPV-positive patients. Clinical trials are necessary to confirm the clinical relevance and efficacy of ADCs targeting TROP2 and Nectin-4 in OSCC treatment.

Human papillomavirus (HPV)—associated oropharyngeal cancer (OPC) is increasing, with HPV16 being the most prevalent type. Persistent oral HPV infections play a causal role in the pathogenesis of these cancers. The objective of this systematic review was to summarize current data on oral HPV prevalence in the general population and in people living with HIV (PLWH), possible effects of prophylactic vaccination and optimal sampling methods for the detection of HPV in the oral cavity. We searched Medline and Livivo for publications on oral HPV prevalence in cohorts > 1000 individuals (> 100 individuals for cohorts of PLWH) released between January 2012 and October 2024. In total, 51 original studies and meta-analyses were included in this review. Overall prevalence of oral HPV infection in general population/healthy individuals was between 0.67 and 11.89

Human papillomavirus-mediated recurrent respiratory papillomatosis (RRP) is a premalignant neoplasia of the upper airway characterized by significant dysphonia and respiratory obstruction. Immune checkpoint blockade has emerged as a potential alternative to repeated surgical interventions in RRP. Here, we investigated the intralesional T-cell composition and expression of the immune checkpoints programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) in RRP. We analyzed tissue samples from 30 patients treated at a tertiary care center between 2009 and 2021, including paired samples from individual patients collected at different time points. Immunohistochemical staining was performed for CD4, CD8, CTLA-4, FoxP3, and PD-L1 and correlated with disease severity and previous adjuvant therapies. Overall disease burden and intervention-free survival were not associated with the abundance of CD4+, CD8+, or FoxP3+ T cells, nor with immune checkpoint expression. However, patients with aggressive disease exhibited a higher intralesional FoxP3/CD4 T-cell ratio. Prior intralesional cidofovir treatment was associated with reduced CD4+ T-cell infiltration. These findings suggest that a locally immunosuppressive microenvironment, reflected by an elevated FoxP3/CD4 ratio, contributes to disease severity in RRP. Consistent CTLA-4 expression across all evaluated samples supports further investigation of anti-CTLA-4 therapy, either alone or in combination with other checkpoint inhibitors.

The field of otorhinolaryngology and head and neck surgery comprises both conservative and surgical domains. Specialist training is often followed by in-depth surgical specialization, in the past reflected by, among other things, continued education in "specialized surgical otorhinolaryngology." This qualification was discontinued, however, by the German Medical Association's reform of the continuing medical education (CME) regulations ([Muster-]Weiterbildungsordnung, MWBO, 2003). Although it is still possible to obtain additional certification in "plastic and esthetic surgery," another advanced surgical qualification in, for example, oncology, otology, or rhinology, is currently not possible within the scope of the WBO of the medical associations. It would not appear possible to implement additional (Sect. C of the WBO) or specialist (Sect. B) CME qualifications in the near future, despite the fact that surgical specialization-in light of the necessity of sustainable quality assurance (e.g., certified cancer centers, cochlear implantation facilities, skull base centers) or the fundamental changes to the healthcare landscape (hospital reform)-seems more important than ever. On the initiative of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the German Academy of Oto-Rhino-Laryngology (DAHNO), a concept to enable expert certification is to be developed in collaboration with specialist working groups. This initiative initially addresses "head and neck surgical oncology" as well as perspectives for "oto- and lateral skull base surgery" and "rhino- and anterior skull base surgery." Relevant content is stored in a logbook. The goal is to present the applicants' expertise in "head and neck surgical oncology" analogously to international standards. The certificate can be used as evidence of individual oncosurgical skills, e.g., for other certification procedures. The practical implementation is carried out by an independent certification body (ClarCert GmbH) on behalf of the DGHNO-KHC in collaboration with the DAHNO and the Oncology Working Group. Applications for the expert certificate "head and neck surgical oncology" are now open for members of the DGHNO-KHC and the DAHNO.

Head and neck squamous cell carcinoma (HNSC) accounts for 450.000 deaths worldwide each year. Rising cases of HNSC have been predicted. Understanding the tumor biology in patients is crucial to developing more efficient treatment strategies against HNSC. Especially in the context of immunotherapy, the interplay of immune, cancer and stroma cells in the tumor microenvironment (TME) strongly influences the biological characteristics and behavior of the tumor and its response to therapy. However, most HNSC in vitro models such as patient-derived cell lines and organoids do not recapitulate TME complexity. Patient-derived tumor fragments (PDTFs) are a novel pre-clinical model to bridge this gap. Isolated directly from patients, they preserve the spatial and cellular tumor composition, allowing analysis of tumor behavior and reaction to treatment in the context of the TME. In this study, we adapted the PDTF methodology to study the effects of combined chemo- and immunotherapy on HNSC. To generate PDTFs, tumors from patients with HPV-negative HNSC were extracted in routine surgery and immediately transferred to the lab. The tumors were mechanically dissected into 1 mm3 fragments, termed PDTFs. Several PDTFs per tumor were distributed across wells of a cell culture plate and subjected to different treatments with cisplatin, nivolumab or caspase inhibition as well as combinations. After short-term ex vivo culture of max. 72h, we performed gene expression analysis via qPCR and RNA-seq as well as histological analysis of PDTFs. In total, PDTFs from 14 different HNSCs could be subjected to treatment, including 2 longitudinal biopsies from the same patient. Histological analysis of freshly extracted PDTFs showed the intact TME ex vivo. Transcriptomic analysis revealed a significant reaction to treatment that was consistent with previous in vitro results. HALLMARK gene sets involved in cell cycle progression (Mitotic spindle, G2M Checkpoint, E2F Targets), EMT as well as glycolysis were downregulated, while inflammatory signaling-related gene sets were enriched, especially in the combined treatment with immunotherapy. Additionally, increased IFNγ expression indicates specific effect of the immunotherapy on leucocytes in the TME. Matched PDTFs from the same patient showed strong correlation of transcriptomic behavior. Overall, we could show treatment-specific reaction of the PDTFs to both chemotherapy and immunotherapy, that included effects on cell cycle, metabolism and inflammation. The measurable reaction of the leucocytes within the TME sets this model apart from other ex vivo models. Together with the patient-specific differences in transcriptomic behaviour, evident in the matched PDTFs, this makes PDTFs an interesting ex vivo model whose application for patient-specific treatment prognosis will be the subject of further studies. Mareike S. Haarmann, Philipp Zimmermann, Malte Suchan, Dominik Funken, Jens Peter Klußmann, Johannes Brägelmann. Analyzing treatment effects of chemo- and immunotherapy in the context of the TME in an ex vivo model of HNSC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3928.

Ultrasound-guided fine-needle aspiration cytology (FNAC) is a widely used diagnostic procedure which facilitates the differentiation of salivary gland lesions. Although the performance of salivary gland FNAC (SG-FNAC) has improved since the introduction of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the range of the reported performance is still wide. Therefore, the aim of this study was to determine lesion- and sampling-related factors that influence the success of SG-FNAC. All SG-FNAC cases performed in a tertiary referral hospital between September 1st, 2011, and August 31st, 2022, were retrospectively identified. Demographic, histopathological, lesion-specific, and sampling-related data were retrieved from the clinical charts. Cytopathological reports were categorized according to the MSRSGC. The risk of malignancy (ROM), the performance measures, and factors influencing the success of SG-FNAC were calculated. Overall, 1289 cases with histopathological follow-up diagnosis (out of 1952 SG-FNACs) were included. The ROM was: non-diagnostic = 23.9

The aim of this study was to analyze gender distribution among speakers, presenters, and session chairs at the annual meetings of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC).Scientific programs of the DGHNO-KHC annual meetings from 2013 to 2024 were retrieved from the society's website. The specialty area of each contribution as well as the gender and role of speakers and individuals in leadership functions were recorded.Of all 10950 contributions, 34.0% were presented by women. While the proportion of women in poster sessions was 44.4%, it was significantly lower for oral presentations (31.5%) and symposia (14.6%). The overall proportion remained stable over the 12-year period (p=0.669); however, the proportion of women in leadership roles increased (from 9.2% to 23.0%, p<0.001), as did the share of awards and honors going to women (from 22.0% to 32.3%, p<0.001). Women were particularly represented in the fields of gender studies (100%) and psychosomatics (50%), but were underrepresented in technical-surgical specialties.The proportion of female presenters at DGHNO-KHC meetings has stagnated at a low level over the past twelve years. In particular, representation in speaking roles and leadership positions remains limited. Targeted measures such as mentoring, increased involvement in organizing committees, and diversity-conscious selection processes are necessary to further promote gender diversity and address structural inequalities.

Introduction Sleep disordered breathing encompasses a spectrum of disorders ranging from simple snoring to severe obstructive sleep apnea. The burden of disease is falling disproportionately on high-income countries. If left untreated, obstructive sleep apnea has negative long-term health consequences such as increased risk of hypertension, diabetes, obesity, cardiovascular disease, depression, heart attack, traffic and work accidents, dementia, and stroke. The aim of this study was to determine the prevalence of snoring, pauses in breathing during sleep, and obstructive sleep apnea syndrome in Germany and to examine the association of these events with body mass index and other sociodemographic variables.

Purpose. Ultrasound-guided fine-needle aspiration cytology (FNAC) is a widely used diagnostic procedure which facilitates the differentiation of salivary gland lesions. Although the performance of salivary gland FNAC (SG-FNAC) has improved since the introduction of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the range of the reported performance is still wide. Therefore, the aim of this study was to determine lesion- and sampling-related factors that influence the success of SG-FNAC. Methods. All SG-FNAC cases performed in a tertiary referral hospital between September 1st, 2011, and August 31st, 2022, were retrospectively identified. Demographic, histopathological, lesion-specific, and sampling-related data were retrieved from the clinical charts. Cytopathological reports were categorized according to the MSRSGC. The risk of malignancy (ROM), the performance measures, and factors influencing the success of SG‑FNAC were calculated. Results. Overall, 1,289 cases with histopathological follow-up diagnosis (out of 1,952 SG-FNACs) were included. The ROM was: non-diagnostic = 23.9%, non-neoplastic = 4.4%, atypia of undetermined significance (AUS) = 34.5%, neoplasm-benign = 1.0%, neoplasm‑salivary gland neoplasm of uncertain malignant potential (SUMP) = 15.3%, suspicious for malignancy = 74.1%, malignant = 96.2%. The sensitivity, specificity, accuracy, positive, and negative predictive value for differentiating benign from malignant lesions (excluding lesions categorized as AUS and SUMP) were 87.5%, 97.7%, 96.3%, 85.0%, and 98.1%, respectively. A larger lesion size (OR (95% CI) =1.21 (1.06-1.39), p = 0.004), a higher number of obtained slides (OR (95% CI) = 1.31 (1.17-1.46), p < 0.001), and the physician performing the FNAC (p = 0.047) were independent predictors for a higher success, while localization of the lesion within the submandibular compared to the parotid gland (OR (95% CI) = 0.38 (0.19-0.77), p = 0.008) was an independent predictor for lower success of SG-FNAC. Conclusion. This is the largest single-center study evaluating SG-FNAC performance to date. It identified independent lesion- and sampling-related factors influencing the success of SG‑FNAC. Knowledge of those can improve performance of the procedure.

INTRODUCTION:Cholesteatoma, a challenging entity in otologic surgery, necessitates a standardized classification system for effective communication among healthcare providers and consistent reporting of surgical outcomes. The ChOLE Classification System, introduced by Linder et al., stages cholesteatoma based on extension (Ch), ossicular chain status (O), life-threatening complications (L), and Eustachian tube function and mastoid pneumatization (E). METHODS:We classified 199 patients who underwent cholesteatoma surgery between 2019 and 2023 in our University Hospital to assess the distribution of the ChOLE stages and to examine the relationship between the ChOLE stages and the duration of surgery. RESULTS:This study revealed significant correlations between the ChOLE stage and respective subgroups of the classification and duration of surgery and thus complexity of procedure. CONCLUSION:Despite limitations, the ChOLE classification proves valuable in predicting surgical complexity and optimizing patient care. Further research is warranted to validate these findings and enhance cholesteatoma management strategies.

Einleitung Der Eigenfetttransfer beinhaltet die Entnahme und Transplantation von autologem Fett zur Verbesserung von Kontur und Form am Zielort. In der Kehlkopfrekonstruktion bietet autologes Fett gegenüber allogenen Materialien Vorteile aufgrund seiner Biokompatibilität, Verfügbarkeit und Anpassungsfähigkeit. Die Anwesenheit von Fettstammzellen (ASC) trägt zu besseren Ergebnissen bei, indem sie das Überleben des Transplantats fördern. Ursachen, die Langzeitergebnisse negativ beeinflussen, wie die variable Fettresorption, bleiben jedoch unklar.