[Update: Epidemiology and Prevention of Oropharyngeal Cancer]. / Update: Epidemiologie und Prävention des Oropharynxkarzinoms.

Due to the association with the causal HPV-16 infection, the oropharyngeal carcinoma spreads into two separate entities depending on HPV-16 positivity. More recent data show a diversified picture of the importance and prevalence of the surrogate parameter p16 (discordance) for a definitive HPV-16 association, which varies worldwide. In the context of prevention options, vaccination is of major and HPV screening of healthy people only of little importance.

Consultation Requests and Satisfaction with a Telehealth Network for Epilepsy: Longitudinal Analysis of the Epilepsy Network Hessen Evaluation.

Background: Telemedicine improves access to specialized medical expertise, as required for paroxysmal disorders. The Epilepsy Network Hessen Evaluation (ENHE) is a pilot cross-sectoral teleconsultation network connecting primary neurologists and pediatricians with epilepsy centers in Hessen, a federal German state. Methods: We prospectively and longitudinally evaluated telehealthcare in the ENHE. Participating physicians rated each consultation for satisfaction and impact on further management. The survey was administered at each consultation and 3 months later. Results: We analyzed 129 consultations involving 114 adult and pediatric patients. Their mean age was 34 years (standard deviation: 26, range: 0.1-91 years), 48% were female, and 34% were children and adolescents. The most common consultation requests were co-evaluation of an electroencephalogram (electroencephalogram [EEG]; 76%) and therapeutic (33%) and differential diagnosis (24%) concerns. Physicians transmitted one paraclinical examination on average (range: 1-4), predominantly EEG (85%), followed by magnetic resonance imaging (17%) and written records (9%). Response rates were 72% for the initial and 67% for the follow-up survey. Across respondents, 99% (n = 92) were satisfied with the ENHE. Overall, 80% of the consultations contributed to the diagnosis, and 90% were considered helpful for treatment, influencing it in 71% of cases. Seizure frequency had decreased more often (96%) than increased (4%) at 3 months. The initial diagnosis was confirmed in 78% of patients. Discussion: In this pilot teleconsultation network for paroxysmal disorders, diagnostic and therapeutic advice was perceived as helpful. Clinical outcomes were largely positive, suggesting tele-epileptology is viable for paroxysmal (seizure) disorders.

Generation of a Realistic Synthetic Laryngeal Cancer Cohort for AI Applications.

BACKGROUND: Obtaining large amounts of real patient data involves great efforts and expenses, and processing this data is fraught with data protection concerns. Consequently, data sharing might not always be possible, particularly when large, open science datasets are needed, as for AI development. For such purposes, the generation of realistic synthetic data may be the solution. Our project aimed to generate realistic cancer data with the use case of laryngeal cancer. METHODS: We used the open-source software Synthea and programmed an additional module for development, treatment and follow-up for laryngeal cancer by using external, real-world (RW) evidence from guidelines and cancer registries from Germany. To generate an incidence-based cohort view, we randomly drew laryngeal cancer cases from the simulated population and deceased persons, stratified by the real-world age and sex distributions at diagnosis. RESULTS: A module with age- and stage-specific treatment and prognosis for laryngeal cancer was successfully implemented. The synthesized population reflects RW prevalence well, extracting a cohort of 50,000 laryngeal cancer patients. Descriptive data on stage-specific and 5-year overall survival were in accordance with published data. CONCLUSIONS: We developed a large cohort of realistic synthetic laryngeal cancer cases with Synthea. Such data can be shared and published open source without data protection issues.

Cancer-associated financial burden in German head and neck cancer patients.

Background: The financial toxicity of cancer causes higher morbidity and mortality. As the financial burden due to head and neck cancer (HNC) in European healthcare systems with legally established compulsory health insurance is still poorly understood, we set up an investigation to assess the financial impact of HNC. Methods: Between August 2022 and March 2023, HNC consecutive patients (n = 209) attending the cancer aftercare program of a university hospital in an outpatient setting were surveyed utilizing self-administered questionnaires about their socioeconomic situation, income loss, and out-of-pocket payments (OOPPs). Results: The majority of HNC patients (n = 119, 59.5%) reported significant financial burden as a consequence of OOPP (n = 100, 50.0%) and/or income loss (n = 51, 25.5%). HNC patients reporting financial burden due to OOPP had on average 1,716 € per year costs related to their disease, whereas patients reporting an income loss had a mean monthly income loss of 620.53 €. Advanced UICC (7th edition, 2017) stage, T3 or T4 category, and larynx/hypopharynx cancer are significant predictors of financial burden. Conclusion: HNC survivors suffer from significant financial burden after HNC treatment, even in Germany with a healthcare system with statutory health insurance. The findings from this study offer valuable insights for healthcare professionals and policymakers, helping them acknowledge the economic impact of HNC.

Tolerability and efficacy of the cancer vaccine UV1 in patients with recurrent or metastatic PD-L1 positive head and neck squamous cell carcinoma planned for first-line treatment with pembrolizumab - the randomized phase 2 FOCUS trial.

Background: Globally, head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignancy. Despite aggressive multimodal treatment approaches, recurrent and/or metastatic (R/M) disease develops in >50% of patients. In this setting, pembrolizumab was approved for patients with PD-L1 expression. However, response rates with checkpoint inhibitor monotherapy remain limited and strategies to strengthen tumor-directed immune responses are needed. Objective: The FOCUS trial is designed to estimate the effectiveness of UV1 vaccination in combination with pembrolizumab versus pembrolizumab as a single agent in patients with R/M HNSCC. Methods and analysis: The FOCUS trial is a two-armed, randomized, multicenter phase II study which was designed to evaluate the efficacy and feasibility of the hTERT-targeted cancer vaccine UV1 as add-on to pembrolizumab in the 1st line treatment of patients with R/M PD-L1 positive (combined positive score ≥1) HNSCC. Secondary objectives are the exploration of patient subgroups most likely deriving benefit from this novel combination and the establishment of liquid biopsy tumor monitoring in HNSCC. Ethics and dissemination: This clinical study was designed and will be conducted in compliance with Good Clinical Practice and in accordance with the Declaration of Helsinki. It is intended to publish the results of this study in peer-reviewed scientific journals and to present its content at academic conferences. Conclusions: A significant number of patients with R/M HNSCC are frail and may not tolerate chemotherapy, these patients may only be suitable for pembrolizumab monotherapy. However, long term disease stabilizations remain the exception and there is a need for the development of efficacious combination regimens for this patient population. The FOCUS study aims to optimize treatment of R/M HNSCC patients with this promising new treatment approach. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT05075122, identifier NCT05075122.

A Radiomics-Based Machine Learning Perspective on the Parotid Gland as a Potential Surrogate Marker for HPV in Oropharyngeal Cancer.

BACKGROUND: In treatment of oropharyngeal squamous cell carcinoma (OPSCC), human papillomavirus status (HPV) plays a crucial role. The HPV-positive subtype tends to affect younger patients and is associated with a more favorable prognosis. HPV-associated lesions have been described in the parotid gland, which is included in routine imaging for OPSCC. This work aims to explore the ability of an ML system to classify HPV status based on imaging of the parotid gland, which is routinely depicted on staging imaging. METHODS: Using a radiomics approach, we investigate the ability of five contemporary machine learning (ML) models to distinguish between HPV-positive and HPV-negative OPSCC based on non-contrast computed tomography (CT) data of tumor volume (TM), locoregional lymph node metastasis (LNM), and the parotid gland (Parotid). After exclusion of cases affected by streak artefacts, 53 patients (training set: 39; evaluation set: 14) were retrospectively evaluated. Classification performances were tested for significance against random optimistic results. RESULTS: The best results are AUC 0.71 by XGBoost (XGB) for TM, AUC 0.82 by multi-layer perceptron (MLP) for LNM, AUC 0.76 by random forest (RF) for Parotid, and AUC 0.86 by XGB for a combination of all three regions of interest (ROIs). CONCLUSIONS: The results suggest involvement of the parotid gland in HPV infections of the oropharyngeal region. While the role of HPV in parotid lesions is under active discussion, the migration of the virus from the oral cavity to the parotid gland seems plausible. The imaging of the parotid gland offers the benefit of fewer streak artifacts due to teeth and dental implants and the potential to screen for HPV in cases of an absent or unlocatable tumor. Future investigation can be directed to validation of the results in independent datasets and to the potential of improvement of current classification models by addition of information based on the parotid gland.

Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome.

Background: Immune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or high risk of recurrence the potential benefits from adding nivolumab to post-operative radiotherapy or pembrolizumab to cisplatin-based radio-chemotherapy. Methods: Along five randomized controlled ICB trials including NadiHN and ADRISK, blood samples were taken before and after starting ICB in n=25 patients. Concentrations of vascular endothelial growth factor A (VEGF), CCL2 (MCP-1), interleukin-6 (IL-6), IL-8, interferon-gamma (IFN-γ), and CXCL10 (IP-10) pre- and post-ICB in EDTA-anticoagulated plasma and serum were compared. We used receiver operating characteristic (ROC) curves to identify optimal cutoff for defining subgroups before analyzing overall survival (OS) applying Kaplan-Meier plots and multivariate Cox regression. Results: We detected huge heterogeneity between cytokine patterns in pre-and post-ICB plasma and serum. We observed high correlation between concentrations of some cytokines. Despite absent systematic OS differences after ICB with pembrolizumab or nivolumab or between LA-HNSCC versus R/M HNSCC patients, we noticed improved outcome of patients having lower IFN-γ concentrations pre- and post-ICB and following ICB reduced concentrations of VEGF, IL-6, and IL-8 but not MCP-1. Contrarily, increases in IL-6, IL-8, and VEGF levels correlated with impaired outcome. Multivariate Cox regression revealed five independent OS predictors among cytokines; using natural logarithms of their hazard ratios to estimate an individual's risk of dying, three cytokine-expression pattern (CEP)-risk groups with no death within mean (95% confidence interval) follow-up of 29.2 (22.1-36.2) months and median OS of 11.3 (8.8-13.8) and 2.9 (0.4-5.4) months were found. Conclusion: Whereas individual pre- or post-ICB cytokine concentrations in serum or plasma alone failed to predict the survivor group, CEP-risk groups may support the identification of individual patients with long-lasting benefit from ICB.

[Therapy of tumor recurrences or secondary carcinomas in pretreated area is not compatible with the primary therapy in non-previously treated tissue - an overview]. / Die Therapie von Tumorrezidiven bzw. Zweitkarzinomen in vorbehandeltem Gebiet ist nicht mit der Primärtherapie in nicht-vorbehandeltem Gewebe gleichzusetzen ­ eine Übersicht.

There are different initial situations in the treatment of local or locoregional recurrences, secondary carcinomas or residual squamous cell carcinomas of the head and neck region after primary therapy. The majority of patients with locoregional recurrences have had prior treatment consisting of surgery and/or postoperative radiotherapy or radiochemotherapy or primary radiotherapy or radiochemotherapy. In any case, it is a matter of new tumor growth in a previously treated area, which must be taken into account for the therapy decision. The biological backgrounds are diverse and are described in more detail and clinically classified in the present work.

Is High-Risk Sexual Behavior a Risk Factor for Oropharyngeal Cancer?

(1) Background: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). A highly influential case-control study by D'Souza et al. comparing OPSCC patients and ENT patients with benign diseases (hospital controls) established HR-SB as a putative etiological risk factor for OPSCC. Aiming to replicate their findings in a nested case-control study of OPSCC patients and propensity score (PS)-matched unaffected controls from a large population-based German cohort study, we here demonstrate discrepant findings regarding HR-SB in OPSCC. (2) Methods: According to the main risk factors for HNSCC (age, sex, tobacco smoking, and alcohol consumption) PS-matched healthy controls invited from the population-based cohort study LIFE and HNSCC (including OPSCC) patients underwent interviews, using AUDIT and Fagerström, as well as questionnaires asking for SB categories as published. Afterwards, by newly calculating PSs for the same four risk factors, we matched each OPSCC patient with two healthy controls and compared responses utilizing chi-squared tests and logistic regression. (3) Results: The HNSCC patients and controls showed significant differences in sex distribution, chronologic age, tobacco-smoking history (pack years), and alcohol dependence (based on AUDIT score). However, PS-matching decreased the differences between OPSCC patients and controls substantially. Despite confirming that OPSCC patients were more likely to self-report their first sexual intercourse before age 18, we found no association between OPSCC and HR-SB, neither for practicing oral-sex, having an increased number of oral- or vaginal-sex partners, nor for having casual sex or having any sexually transmitted disease. (4) Conclusions: Our data, by showing a low prevalence of HR-SB in OPSCC patients, confirm findings from other European studies that differ substantially from North American case-control studies. HR-SB alone may not add excess risk for developing OPSCC.

[Recommendations of the German Society of Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) for the granting of resident training program authorizations]. / Empfehlungen der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC) für die Erteilung der fachspezifischen Weiterbildungsbefugnis.

The 2018 template for otorhinolaryngology specialist training of the German Medical Association is increasingly implemented by the federal associations. In this regard, the German Society recommended an otorhinolaryngology resident training plan for Otorhinolaryngology, Head and Neck Surgery (DGHNO-KHC) together with the Professional Association of German Otorhinolaryngologists as a suggested guideline for the federal medical associations. In this context, the state medical associations currently work on criteria on the basis of which otorhinolaryngologists and their training institutions can be granted authority for such a certified otorhinolaryngology resident training program.The DGHNO-KHC last made recommendations for the granting of authorizations for specialist training in otorhinolaryngology in 1999. Many contents have changed as a result of the 2018 model specialist training regulations. Therefore, a scientifically formulated proposal for the granting of continuing education authorizations is herewith provided as recommendation to the federal state medical associations.

Imaging in children with hearing loss. / Bildgebende Diagnostik bei Schwerhörigkeit im Kindesalter.

BACKGROUND: Since the introduction of hearing screening in Germany in 2009, pediatric hearing disorders are detected at an early stage. Early therapy is essential for language development. Imaging plays a central role in diagnosis and therapy planning. METHOD: Imaging findings of the most relevant causes of pediatric hearing disorders are presented. Specific attention is given to the method used in each case - CT or MRI. RESULTS AND CONCLUSIONS: While CT is the method of choice for conductive hearing loss, a combination of CT and MRI with high-resolution T2-3D sequences has been established as the best diagnostic method for sensorineural hearing loss. The most common causes of conductive hearing loss in childhood are chronic inflammation and cholesteatoma. Congenital malformations of the outer or middle ear are less frequent. In the case of sensorineural hearing loss, the cause is located in the inner ear and/or the cochlear nerve or the cerebrum. In these cases, congenital malformations are the most common cause. KEY POINTS: · CT and MRI are necessary to identify morphological causes of hearing disorders and to clarify the possibility of hearing-improving ear surgery or cochlear implantation.. · Contraindications for surgical procedures must be excluded.. · Anatomical variants that may be risk factors for surgery must be described.. CITATION FORMAT: · Sorge I, Hirsch F, Fuchs M et al. Imaging diagnostics for childhood hearing loss. Fortschr Röntgenstr 2023; 195: 896 - 904.

Postoperative adjuvant radiochemotherapy with cisplatin versus adjuvant radiochemotherapy with cisplatin and pembrolizumab in locally advanced head and neck squamous cell carcinoma- the study protocol of the Adrisk trial.

Most of the patients with head and neck squamous cell carcinoma (HNSCC) are diagnosed with locally advanced disease. Standards of care for curative-intent treatment of this patient group are either surgery and adjuvant radio(chemo)therapy (aRCT) or definitive chemoradiation. Despite these treatments, especially pathologically intermediate and high-risk HNSCC often recur. The ADRISK trial investigates in locally advanced HNSCC and intermediate and high risk after up-front surgery if the addition of pembrolizumab to aRCT with cisplatin improves event-free sur-vival compared to aRCT alone. ADRISK is a prospective, randomized controlled investiga-tor-initiated (IIT)-phase II multicenter trial within the German Interdisciplinary Study Group of German Cancer Society (IAG-KHT). Patients with primary resectable stage III and IV HNSCC of the oral cavity, oropharynx, hypopharynx and larynx with pathologic high (R1, extracapsular nodal extension) or intermediate risk (R0 <5 mm; N≥2) after surgery will be eligible. Two hun-dred forty patients will be randomly assigned (1:1) to either standard aRCT with cisplatin (standard arm) or aRCT with cisplatin + pembrolizumab (200 mg iv, in 3-week cycle, max. 12 months) (interventional arm). Endpoints are event-free and overall survival. Recruitment started in August 2018 and is ongoing.