University Hospital for Otorhinolaryngology (ENT)

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and spatial gene expression analysis, clinical outcomes research, computer aided surgery, epithelial-mesenchymal transition, head and neck cancer, inner ear disorders, oncolytic viruses, Otorhinolaryngology, radiomics, and sleep related breathing disorders

Diagnosis, decision-making, innovative treatments, precision medicine and quantitative state-of-the art treatment outcome. Tumour biology supports clinical management of patients via predicting therapy resistance. Tumour-stroma interaction, metabolic modifiers of tumour immune system and immunotherapy support clinical decisions. Artificial intelligence approaches support clinical decisions. Inner ear research focuses on hearing including computer simulations of neural hearing and equilibrium.

The University Hospital for Otorhinolaryngology is the healthcare provider for the greater Tyrolean area. It has three operating theatres, three wards with 41 beds and an outpatient clinic. On average, 2,800 inpatients and over 33,000 outpatients are treated every year. As well as all standard otorhinolaryngologic surgical procedures (Fig. 1), we provide cochlear implants, hypoglossal implants, sialendoscopy and Eustachian tube dilation. Our state-of-the-art technical facilities include intraoperative navigation, neuro-monitoring and various laser types such as CO₂, KTP and Erbium laser. We are one of only three certified centres for Head and Neck cancer in Austria and work closely with the University Hospital for Maxillofacial Surgery.

We have three clinical research laboratories, the clinical head and neck cancer registry (with over 1,200 entries), the chronic rhinosinusitis patient registry (with over 300 patients) and the scientific biobank (containing samples of tumours (230), diseased paranasal sinus mucosa (100) and healthy control samples (80) at -190 °C). Our biobank consists of over 800 tumour and 300 paranasal sinus FFPE samples.

Inner Ear

Glückert, A. Schrott-Fischer

Our main research focuses on human inner ear development, congenital abnormalities and auditory nerve regeneration. Basic research on age related hearing loss and finding improvements for electrical stimulation of the auditory and vestibular nerve with organ explant and cellular models as well as computer simulations based on high-resolution 3D datasets bridge our research to cochlear implant companies. Comparative analysis of several mammalian animal models with the human inner ear complete our portfolio for translational inner ear research.

Computer simulation of electrical stimulation in the inner ear: The human inner ear is inaccessibility for physiological studies and necessitates computer-modelling strategies to improve cochlear and vestibular implantations to stimulate the nerves. Advanced correlative imaging techniques, ranging from high-resolution microCT to electron microscopy, deliver unparalleled  morphometric data, automated immunohistochemistry and image analysis. These functional aspects are essential for cellular and finite element modelling.

Regeneration of the cochlear nerve for a gapless man: machine cochlear implant interface: After hair cell loss, auditory neurons survive for decades as monopolar amputated neurons. Regeneration of the peripheral axons and growth towards a cochlear implant will increase stimulations specificity and boost speech understanding. Neurotrophic factors stimulate this outgrowth, as we demonstrated in in-vivo and in-vitro experiments.

Inner ear development: It is vital to understand the mechanisms of inner ear regeneration and the signalling pathways. This requires knowledge of the cell fate and differentiation during embryology and foetal development. The function of neurotrophin brain-derived neurotrophic factor (BDNF) its receptors and its associated factors in developing human inner ear is a particular research focus.

Tumour Biology

J. Dudas, J. Federspiel, M. do Carmo Greier, S. Dichtl-Zweimüller, F. Johnson, R. Hartl, L. Schmutzler, A. Stenzl, M.s Santer, D. Dejaco, V. Schartinger, V. Strasser, T. Steinbichler

This group’s primary focus is on supporting the clinical management of head and neck cancer patients. We determine predictive factors for therapy resistance, investigate the mechanisms of resistance and propose palliative therapy to overcome the resistance. Investigations of tumour-stroma interaction and metabolic modifiers of the tumour immune system and immunotherapy are exploring new clinical routes. Molecular pathways of neurotrophin regulation of the developing human inner ear are explored in the context of head and neck cancers.

Neurotrophins in the developing inner ear and in HNSCC: This project was supported by the Austrian Science Fund and is now completed. A subsequent project is planned. The project investigated the quantitative gene expression changes of neurotrophin BDNF and other neurotrophins at the mRNA level by using real-time PCR and next generation sequencing RNASeq in the developing human inner ear. BDNF-associated factors and BDNF receptors are co-analysed in the bioinformatics follow-up of the RNASeq data. Gene ontology and interactive prediction models as KEGG- and WIKI pathways allow investigation of the co-expression and bio-mechanistic patterns of neurotrophins and associated genes in the timeline of human cochlea development. The next project will focus on the examination of the tumour-neuronal interaction in the invasivity of head and neck cancer.

The project “Predictive markers of immune checkpoint therapy” focuses on the escape of tumour cells from an activated local immune system in melanoma and head and neck squamous carcinoma. This project was supported by the Austrian Science Fund (FWF), and a subsequent project proposal is submitted to FWF. This research will support the development of neoadjuvant immunotherapy in head and neck cancer.

Permissivity and mode of action of oncolytic viruses in ex vivo samples and slice cultures of human head and neck cancer studies in a preclinical environment, a live recombinant oncolytic virus with an interferon-dependent tumour specificity induced oncolysis and stimulation of antitumour immune activity in permissive solid tumours without relevant neurotoxicity. The Molecular Oncology Lab of the ENT-clinic Innsbruck is providing patients-derived research material for VSV-GP permissivity studies by ViraT. It is also focusing on the function of tumour-infiltrating immune cells. We area also investigating the effects of metabolic and nutritional conditions and the influence of microbiome products (short chain fatty acids) on the functionality and anti-tumour effects of the local immune system.

Exosomes in head and neck squamous cell carcinoma are extracellular vesicles that may deliver components that cause resistance to standard therapy in head and neck cancer. Their cargo contains proteins involved in signalling pathways, RNA and microRNA, and even double-stranded DNA. We hypothesise that EMC-exosomes play a key role in disseminating therapy resistance in HNC.

Targeting of factors responsible for therapy resistance in head and neck cancer: the scattered, clustered and diffuse detection of slug in a pre-therapy biopsy is key to predict radio-chemotherapy resistance, allowing surgery as a possible first-line therapy. The stabilised slug achieves protein interaction-based support of DNA-damage repair, which is unrelated to its transcription repressor activity. Our next research will focus on slug-stabilisers and the suppression of slug by microRNA mimics or inhibitors to provide effective therapy extension to up-front surgery for slug-positive HNC patients.

Surgeons and patients alike are in the dark about salivary gland tumour entities preoperatively, despite significant advances in medicine. A reliable preoperative examination to assess the dignity of a salivary gland tumour is currently not available in medicine. There have been only a few advances in this field of research recently. We are determined to make it possible to identify salivary gland tumours sensitively and precisely. This would allow surgeons to plan the extent of the required intervention better and to inform patients in detail before surgery. It would also make preoperative planning much easier. This project, supported by the Tyrol Medical Research Fund, precisely processes salivary gland tumours using immunocytometry, immunohistochemical and molecular biological methods.

Photodynamic therapy (PDT) involves using photosensitisers (PS) that are activated by laser light. This releases reactive oxygen species (ROS) that can cause cell damage. The PS have two important properties: they react with cell components and enable the release of ROS only when irradiated with the corresponding light wavelength. This project is designed to specifically accumulate PS in tumour cells, with a particular focus on the interface between tumour cells and cancer-associated fibroblasts (CAFs). To achieve this goal, we conjugate a PS (photochlorine, HPPH), which will induce tumour cell death, with a fibroblast-activating protein (FAP)-binding target structure. In clinical application, we plan PDT for out-of-therapy head and neck cancer patients. With PS targeting and newly developed pulse-frequency lasers (PFL), we develop an effective therapy option for head and neck cancer patients. The University Clinic of Otorhinolaryngology (ENT) and the University Clinic of Nuclear Medicine (UCN) of the Medical University of Innsbruck (MUI) and Heltschl Medizintechnik GmbH are the key partners in this project.

Radiomics and Artificial Intelligence

Z. Bardosi, D. Dejaco, W. Freysinger, Y. Özbek, M. Regodic, M. Santer, S. Naccour, A. Lukes, S. Aljani

The main research of this group focuses on providing tools to surgeons to aid intraoperative orientation and general decisions in microscopic surgery.

Today, surgical placement of auditory brain stem implants has become a routine intervention. However, there is still ample space for improvement in the human computer interaction in surgery. A joint MED-EL and FFG sponsored project demonstrated that intuitive computer interfaces for surgeons are of significant value during such procedures. The paradigms of acoustic and visual guidance were developed and evaluated in a preclinical setting, respectively. The tools received very satisfactory feedback from surgeons and may eventually provide a roadmap for further exploitation.

We are also working to identify anatomical structures in the live stereo-microscopic view of the surgical site. This will be done autonomously and in real-time. Our innovative navigation technology is the best on the market. It is highly accurate and uses deep learning to calibrate and identify anatomical structures. This technology is pushing the current limits of navigation and knowledge / information support in the petrous bone and beyond.

Machine learning as a clinical decision support tool is a new technology that assist in classifying clinical decision pathways. The objective of this project is to pinpoint the most relevant features in diagnostic CT imaging of ENT tumour patients. This will enable us to swiftly identify potential non-responders or provide valuable insights for optimised clinical treatment. This could include surgery, radio- and chemotherapy or combinations thereof.

The research field has recently been extended to include AI and deep learning. This is a collaborative project with the Univ. Hospital of Radiology, the Department of Interventional Oncology – Stereotaxy and Robotics. The research focuses on fully automatic planning of radio-frequency ablation needles in liver tumours. This provides the surgeons with the optimal plan for maximum coverage of the tumour while avoiding critical anatomical structures in the liver. The approach learns on existing patient cases with standard CT data and can provide individual solutions.

ePRO in Head and Neck

Dejaco, C. Schmit, V. Innerhofer 

The “ePRO in Head and Neck” research group is working on the integration and further development of patient-reported outcome measures (PROMs) in oncology care as part of the research collaboration with the EORTC Quality of Life Group. The aim of the work is to systematically assess the quality of life of oncology patients, integrate their perspectives more closely into clinical decision-making processes, and implement innovative digital data collection strategies – particularly in the head and neck area.

In addition, we conducted a thorough review of quality of life measurement in patients with rare solid tumours. We also investigated the usability of ePROs in older patients and their implementation at oncology referral centres. Building on this work, we are currently planning a prospective multicentre survey and a Delphi study to improve PROM use in routine clinical practice.

Inner Ear

1. Steinacher C, Nishio SY, Usami SI, Dudas J, Rieder D, Rask-Andersen H, et al. Expression of Neurotrophins and Its Receptors During Fetal Development in the Human Cochlea. Int J Mol Sci. 2024;25(23).

2. Giese D, Li H, Liu W, Staxang K, Hodik M, Ladak HM, et al. Microanatomy of the human tunnel of Corti structures and cochlear partition-tonotopic variations and transcellular signaling. J Anat. 2024.

3. Yildiz E, Gadenstaetter AJ, Gerlitz M, Landegger LD, Liepins R, Nieratschker M, et al. Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics. Front Pharmacol. 2023;14:1062379.

4. Stultiens JJA, Lewis RF, Phillips JO, Boutabla A, Della Santina CC, Glueckert R, et al. The Next Challenges of Vestibular Implantation in Humans. J Assoc Res Otolaryngol. 2023;24(4):401-12.

5. Schmidbauer D, Fink S, Rousset F, Lowenheim H, Senn P, Glueckert R. Closing the Gap between the Auditory Nerve and Cochlear Implant Electrodes: Which Neurotrophin Cocktail Performs Best for Axonal Outgrowth and Is Electrical Stimulation Beneficial? Int J Mol Sci. 2023;24(3).

Tumour Biology

1. Liu J, Bewicke-Copley H, Patel S, Emanuel O, Counsell N, Sharma SJ, Schartinger V, Siefer O, Wieland U, Wurdemann N, Garcia-Marin R, Dudas J, Patel D, Allen D, Guppy N, Linares J, Resende-Alves A, Howard DJ, Masterson L, Vaz FM, et al. Exploring targets in oropharyngeal cancer – association with immune markers and AI-scoring of B7-H3 expression. Clin Transl Med. 2025;15(3):e70265. Epub 2025/03/12. doi: 10.1002/ctm2.70265. PubMed PMID: 40071386; PMCID: PMC11897723.

2. Federspiel J, Steinbichler TB, Vorbach SM, Eling MT, Borena W, Seifarth C, Hofauer BG, Dudas J. Patient-Derived Cancer-Associated Fibroblasts Support the Colonization of Tumour Cells in Head and Neck Squamous Cell Carcinoma. Biomedicines. 2025;13(2). Epub 2025/02/26. doi: 10.3390/biomedicines13020358. PubMed PMID: 40002772; PMCID: PMC11852712.

3. Greier MDC, Runge A, Dudas J, Hartl R, Santer M, Dejaco D, Steinbichler TB, Federspiel J, Seifarth C, Konschake M, Sprung S, Sopper S, Randhawa A, Mayr M, Hofauer BG, Riechelmann H. Cytotoxic response of tumour-infiltrating lymphocytes of head and neck cancer slice cultures under mitochondrial dysfunction. Front Oncol. 2024;14:1364577. doi: 10.3389/fonc.2024.1364577. PubMed PMID: 38515569; PMCID: PMC10954813.

4. Greier MDC, Runge A, Dudas J, Carpentari L, Schartinger VH, Randhawa A, Mayr M, Petersson M, Riechelmann H. Optimizing culturing conditions in patient derived 3D primary slice cultures of head and neck cancer. Front Oncol. 2023;13:1145817. doi: 10.3389/fonc.2023.1145817. PubMed PMID: 37064104; PMCID: PMC10101142.

5. Federspiel J, Greier MDC, Ladanyi A, Dudas J. p38 Mitogen-Activated Protein Kinase Inhibition of Mesenchymal Transdifferentiated Tumour Cells in Head and Neck Squamous Cell Carcinoma. Biomedicines. 2023;11(12). doi: 10.3390/biomedicines11123301. PubMed PMID: 38137525; PMCID: PMC10741606.

Radiomics and Artificial Intelligence

1. M. Sadeghi, A. Ramos-Prats, P. Neto, F. Castaldi, D. Crowley, P. Matulewicz, E. Paradiso, W. Freysinger, F. Ferraguti, G. Göbel
Localization and registration of 2D histological mouse brain images in 3D atlas space.
Neuroinformatics, 21(3), 615 – 630 (2023).
https://doi.org/10.1007/s12021-023-09632-8

2. M. Santer, H. Riechelmann, B. Hofauer, J. Schmutzhard, W. Freysinger, A. Runge, T. M. Gottfried, P. Zelger, G. Widmann, H. Kranebitter, S. Mangesius, J. Mangesius, F. Kocher, D. Dejaco
Radiomic assessment of radiation-induced alterations of skeletal muscle composition in head and neck squamous cell carcinoma within the currently clinically defined optimal time Window for salvage surgery — a pilot study.
Cancers 15, 4650 (2023)
https://doi.org/10.3390/cancers15184650

3. Y. Özbek, R. R. Bardosi, W. Freysinger
Noctopus: A novel device and method for patient registration and navigation in image-guided cranial surgery.
Int. J. Computer Assisted Radiology and Surgery, 19, 2371 – 2380 (2024).
https://doi.org/10.1007/s11548-024-03135-w

4. M. Santer, P. Zelger, J. Schmutzhard, W. Freysinger, A. Runge, T. Gottfried, A. Tröger, S. Vorbach, J. Mangesius, G. Widmann, S. Graf, B. Hofauer, D. Dejaco
The Neck-Persistency-Net: A three-dimensional, convolution, deep neural network aids in distinguishing vital from non-vital persistent cervical lymph nodes in advanced head and neck squamous cell carcinoma after primary concurrent radiochemotherapy.
Eur. Arch. Oto-Rhino-Laryngology, 281(11), 5971 – 5982 (2024).
https://doi.org/10.1007/s00405-024-08842-3

5. S. Milosavljevic, Z. R. Bardosi, Y. Özbek, W. Freysinger
Adaptive infrared patterns for microscopic surface reconstructions.
Int. J. Computer Assisted Radiology and Surgery, 19, 2311 – 2319 (2024).
https://doi.org/10.1007/s11548-024-03242-8

ePRO in Head and Neck

1. Exploring the integration of patient-reported outcome measures in clinical practice: A cross-sectional survey of EORTC healthcare professionals.
Lehmann J, Dragan T, Rammant E, de Ligt KM, Lai-Kwon J, Lidington E, Bultijnck R, Dejaco D, Taylor KJ, Gašpert T, Colombo E, Madariaga A, Brandão M, Nicolay JP, Zerdes I, Bosisio F, Correia D, Pellerino A, Marquina G, Fontes-Sousa M, Grisay G, Silva T, Siebenhüner A, Cammarota A, Szturz P.Eur J Cancer. 2025 Mar 1;220:115333. doi: 10.1016/j.ejca.2025.115333. Online ahead of print.

2. Health-Related Quality of Life (HRQoL) Assessments in Research on Patients with Adult Rare Solid Cancers: A State-of-the-Art Review.
Padilla CS, Bergerot CD, Dijke K, Roets E, Boková G, Innerhofer V, Sodergren SC, Mancari R, Bergamini C, Way KM, Sapoznikov O, Burgers JA, Dejaco D, Tesselaar MET, van der Graaf WTA, Husson O; EORTC Quality of Life Group.Cancers (Basel). 2025 Jan 24;17(3):387. doi: 10.3390/cancers17030387.

3. [Pre-implementation of electronic patient-reported outcomes at reference centers for head and neck oncology : A roadmap towards patient-centered digitalization].
Dejaco D, Gottfried T, Santer M, Thurner A, Lehmann J, Riedl D, Rumpold G, Holzner B, Schmutzhard J, Hofauer B.HNO. 2025 Feb;73(2):95-102. doi: 10.1007/s00106-024-01543-7. Epub 2025 Jan 16.

4. Usability of Electronic Patient-Reported Outcome Measures for Older Patients With Cancer: Secondary Analysis of Data from an Observational Single Center Study.
Riedl D, Lehmann J, Rothmund M, Dejaco D, Grote V, Fischer MJ, Rumpold G, Holzner B, Licht T.J Med Internet Res. 2023 Sep 21;25:e49476. doi: 10.2196/49476.

1. Dudas, FWF, Neurotrophins in inner ear and head and neck cancer
2. Dudas, Vira Therapeutics, Permissivity and mode of action of oncolytic viruses in ex vivo slice cultures of human head and neck cancer
3. Dudas, EU – COST, IMMUNO-model – Modelling immunotherapy response and toxicity in cancer
4. Freysinger, FWF, doc.funds IGDT-ART
5. Schrott-Fischer, FWF-DACH, Electric simulation of human hearing nerves – fine-structure-based models for improving hearing implants, 230 k€.
6. Dusdasz and A. Schrott-Fischer, FWF, Neurotrophins in inner ear and head and neck cancer, 250 k€.
7. Glückert R., International FWF-Project: FineCI – Fine-Structured-Based Models for Cochlear Implant Advancement
8. Glückert R., FFG Bridge Project: Vascular Senescence as a Key Factor for Cochlear Health
9. Glückert R., LandTirol/MED-EL-Project: NEURO-GLIA-CI: Peripheral process health and regrowth for cochlear implant candidates

Helge Rask-Andersen, Uppsala University, Uppsala, Sweden

Pascal Senn, Hôpitaux Universitaires de Genève, Geneva, Switzerland

Werner Hemmert, Technical University of Munich, Munich, Germany

Christoph Arnoldner, Medical University of Vienna, Vienna, Austria

Hubert Löwenheim, University of Tübingen, Tübingen, Germany

Shin-ichi Usami, Shinshu University School of Medicine, Matsumoto, Japan

Giovanni Blandino, IRCSS Regina Elena National Cancer Institute, Rome, Italy

Andrea Ladanyi, National Institute of Oncology, Budapest, Hungary

Bozena Smolkova, Lucia Juhasikova, Biomedical Research Center of Slovak Academy of Sciences, Bratislava, Slovakia