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Background: Head and neck cancers (HNC) represent an extremely heterogeneous group of diseases with a poorly predictable therapy outcome. Patient-derived tumor organoids (PDTO) offer enormous potential for individualized therapy testing and a better mechanistic understanding of the main HNC drivers. Methods: Here, we have established a comprehensive molecularly and functionally characterized head and neck organoid biobank (HNOB) recapitulating the clinically relevant subtypes of TP53 mutant and human papillomavirus type 16 (HPV 16) infection-driven HNC. Organoids were exposed to radiotherapy, and responses were correlated with clinical data. Genetically engineered normal and tumor organoids were used for testing the direct functional consequences of TP53-loss and HPV infection. Results: The HNOB consisting of 18 organoid models, including 15 tumor models, was generated. We identified subtype-associated transcriptomic signatures and pathological features, including sensitivity to TP53 stabilization by the MDM2 inhibitor Nutlin-3. Furthermore, we describe an in vitro radio response assay revealing phenotypic heterogeneity linked to the individual patient's treatment outcome, including relapse probability. Using genetically engineered organoids, the possibility of co-existence of both cancer drivers was confirmed. TP53 loss, as well as HPV, increased growth in normal and tumor organoids. TP53 loss-of-function alone was insufficient to promote radiation resistance, whereas HPV 16 oncogenes E6/E7 mediated radiosensitivity via induction of cell cycle arrest. Conclusion: Our results highlight the translational value of the head and neck organoid models not only for patient stratification but also for mechanistic validation of therapy responsiveness of specific cancer drivers. [ABSTRACT FROM AUTHOR]

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background: Tinnitus is one of the most common otologic comorbidities, particularly in older patients with severe hearing loss or deafness. Cochlear implants (CI) have been used for hearing rehabilitation more and more successfully in elderly patients and CI treatment is performed in Germany without an age limit. The aim of this follow-up study was to assess the tinnitus burden in the long-term follow-up of elderly patients with hearing rehabilitation using CI., Material and Methods: This prospective longitudinal study included 15 patients between 72 and 92 years of age with preoperative tinnitus who had been treated unilaterally with a CI for the first time about six years ago. Monosyllabic speech understanding and tinnitus burden were assessed using the Mini-Tinnitus Questionnaire. The results were compared with our previous study 24, focusing on the first six months., Results: Six years postoperatively, there was a nonsignificant increase in monosyllabic understanding to 61.7 ± 26.3%, compared with the results six months postoperatively (p = 0.069). The burden of tinnitus showed a stable low mean of 3.9 ± 3.6 points six years postoperatively, compared with the six-month control (p = 0.689) and significantly reduced compared to the preoperative status with 6.9 ± 6.5 points (p = 0.016)., Conclusion: Hearing rehabilitation by using CI leads to a stable improvement of monosyllabic discrimination in elderly people as well as to a stable reduction of tinnitus burden over years., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)