Structured Reporting of Head and Neck Sonography Achieves Substantial Interrater Reliability.

Purpose Ultrasound examinations are often criticized for having higher examiner dependency compared to other imaging techniques. Compared to free-text reporting, structured reporting (SR) of head and neck sonography (HNS) achieves superior time efficiency as well as report quality. However, there are no findings concerning the influence of SR on the interrater reliability (IRR) of HNS. Materials and Methods Typical pathologies (n=4) in HNS were documented by video/images by two certified head and neck ultrasound instructors. Consequently, structured reports of these videos/images were created by n=9 senior physicians at departments of otolaryngology or maxillofacial surgery with DEGUM instructors on staff. Reports (n=36) were evaluated regarding overall completeness and IRR. Additionally, user satisfaction was assessed by a visual analog scale (VAS). Results SR yielded very high report completeness (91.8%) in all four cases with a substantial IRR (Fleiss' κ 0.73). Interrater agreement was high at 87.2% with very good user satisfaction (VAS 8.6). Conclusion SR has the potential to ensure high-quality examination reports with substantial comparability and very high user satisfaction. Furthermore, big data collection and analysis are facilitated by SR. Therefore, process quality, workflow, and scientific output are potentially enhanced by SR.

Artificial intelligence directed development of a digital twin to measure soft tissue shift during head and neck surgery.

Digital twins derived from 3D scanning data were developed to measure soft tissue deformation in head and neck surgery by an artificial intelligence approach. This framework was applied suggesting feasibility of soft tissue shift detection as a hitherto unsolved problem. In a pig head cadaver model 104 soft tissue resection had been performed. The surface of the removed soft tissue (RTP) and the corresponding resection cavity (RC) was scanned (N = 416) to train an artificial intelligence (AI) with two different 3D object detectors (HoloLens 2; ArtecEva). An artificial tissue shift (TS) was created by changing the tissue temperature from 7,91±4,1°C to 36,37±1,28°C. Digital twins of RTP and RC in cold and warm conditions had been generated and volumes were calculated based on 3D surface meshes. Significant differences in number of vertices created by the different 3D scanners (HoloLens2 51313 vs. ArtecEva 21694, p<0.0001) hence result in differences in volume measurement of the RTC (p = 0.0015). A significant TS could be induced by changing the temperature of the tissue of RC (p = 0.0027) and RTP (p = <0.0001). RC showed more correlation in TS by heating than RTP with a volume increase of 3.1 µl or 9.09% (p = 0.449). Cadaver models are suitable for training a machine learning model for deformable registration through creation of a digital twin. Despite different point cloud densities, HoloLens and ArtecEva provide only slightly different estimates of volume. This means that both devices can be used for the task.TS can be simulated and measured by temperature change, in which RC and RTP react differently. This corresponds to the clinical behaviour of tumour and resection cavity during surgeries, which could be used for frozen section management and a range of other clinical applications.

One pattern analysis (OPA) for the quantitative determination of protein interactions in plant cells.

BACKGROUND: A commonly used approach to study the interaction of two proteins of interest (POIs) in vivo is measuring Förster Resonance Energy Transfer (FRET). This requires the expression of the two POIs fused to two fluorescent proteins that function as a FRET pair. A precise way to record FRET is Fluorescence Lifetime IMaging (FLIM) which generates quantitative data that, in principle, can be used to resolve both complex structure and protein affinities. However, this potential resolution is often lost in many experimental approaches. Here we introduce a novel tool for FLIM data analysis of multiexponential decaying donor fluorophores, one pattern analysis (OPA), which allows to obtain information about protein affinity and complex arrangement by extracting the relative amplitude of the FRET component and the FRET transfer efficiency from other FRET parameters. RESULTS: As a proof of concept for OPA, we used FLIM-FRET, or FLIM-FRET in combination with BiFC to reassess the dimerization and tetramerization properties of known interacting MADS-domain transcription factors in Nicotiana benthamiana leaf cells and Arabidopsis thaliana flowers. Using the OPA tool and by extracting protein BINDING efficiencies from FRET parameters to dissect MADS-domain protein interactions in vivo in transient N. benthamiana experiments, we could show that MADS-domain proteins display similar proximities within dimeric or tetrameric complexes but bind with variable affinities. By combining FLIM with BiFC, we were able to identify SEPALLATA3 as a mediator for tetramerization between the other MADS-domain factors. OPA also revealed that in vivo expression from native promoters at low levels in Arabidopsis flower meristems, makes in situ complex formation of MADS-domain proteins barely detectable. CONCLUSIONS: We conclude that MADS-domain protein interactions are transient in situ and may involve additional, so far unknown interaction mediators. We conclude that OPA can be used to separate protein binding from information about proximity and orientation of the interacting proteins in their complexes. Visualization of individual protein interactions within the underlying interaction networks in the native environment is still restrained if expression levels are low and will require continuous improvements in fluorophore labelling, instrumentation set-ups and analysis tools.

Modulation of PD­L1 expression by standard therapy in head and neck cancer cell lines and exosomes.

Although checkpoint inhibitors (CPI) have recently extended the treatment options and improved clinical response of advanced stage head and neck squamous cell carcinoma (HNSCC), treatment success remains unpredictable. Programmed cell death ligand­1 (PD­L1) is a key player in immunotherapy. Tumor cells, and exosomes derived therefrom, are carriers of PD­L1 and efficiently suppress immune responses. The aim of the present study was to analyze the influence of established therapies on PD­L1 expression of HNSCC cell lines and their exosomes. The HNSCC cell lines, UM­SCC­11B, UM­SCC­14C and UM­SCC­22C were treated with fractionated radiotherapy (RT; 5x2 Gy), cisplatin (CT) and cetuximab (Cetux) as monotherapy, or combined therapy, chemoradiotherapy (CRT; RT and CT) or radioimmunotherapy (RT and Cetux). The expression of PD­L1 and phosphorylated (p)ERK1/2 as a mediator of radioresistance were assessed using western blotting, immunohistochemistry and an ex vivo vital tissue culture model. Additionally, exosomes were isolated from concentrated supernatants of the (un­)treated HNSCC cell lines by size exclusion chromatography. Exosomal protein expression levels of PD­L1 were detected using western blotting and semi­quantitative levels were calculated. The functional impact of exosomes from the (un­)treated HNSCC cell lines on the proliferation (MTS assay) and apoptosis (Caspase 3/7 assay) of the untreated HNSCC cell lines were measured and compared. The HNSCC cell lines UM­SCC­11B and UM­SCC­22B showed strong expression of pERK1/2 and PD­L1, respectively. RT upregulated the PD­L1 expression in UM­SCC­11B and UM­SCC­14C and in exosomes from all three cell lines. CT alone induced PD­L1 expression in all cell lines. CRT induced the expression of PD­L1 in all HNSCC cell lines and exosomes from UM­SCC­14C and UM­SCC­22B. The data indicated a potential co­regulation of PD­L1 and activated ERK1/2, most evident in UM­SCC­14C. Exosomes from irradiated UM­SCC­14C cells protected the unirradiated cells from apoptosis by Caspase 3/7 downregulation. The present study suggested a tumor cell­mediated regulation of PD­L1 upon platinum­based CRT in HNSCC and in exosomes. A co­regulation of PD­L1 and MAPK signaling response was hypothesized.

Exercise elevates serum brain-derived neurotrophic factor in partially remitted depression.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic cytokine implicated in the pathogenesis of major depressive disorder (MDD). In MDD, serum BDNF levels are attenuated. Healthy adults show BDNF elevation after exercise. To investigate activity-dependent BDNF elevation in MDD, thirty-seven participants with partially remitted MDD were allocated to either a bout of strenuous or light activity. Serum was collected before and after the intervention. BDNF was measured using a highly sensitive and specific enzyme-linked immunosorbent assay. Significant BDNF elevation in the strenuous activity group emerged. This study confirms exercise-dependent serum BDNF elevation in MDD. Preregistration: German Clinical Trials Register (DRKS0001515).

[The potential of complementary music interventions in patients with head and neck cancer]. / Das Potenzial komplementärer Musikinterventionen bei Patienten mit malignen Kopf-Hals-Tumoren.

PURPOSE: The established treatment regimen for patients suffering from cancer in the head and neck region often leads to physical and mental health problems and therefore can significantly reduce the quality of life (QoL) in these patients. The available data indicate that additional complementary treatments, such as music interventions, may improve patients' QoL and compliance and reduce symptoms during therapy. METHODS: Anonymous data collection using a self-designed questionnaire was conducted in patients suffering from cancer in the head and neck area in our outpatient department. The questionnaire particularly asked the patients about their need and interest in music interventions during therapy. RESULTS: In total, 138 patients were consecutively enrolled in the study. The mean age was 64.9 years, including 68.1% men and 31.9% women. Only 11.5% listened to music regularly during their therapy at the time of data collection, yet 52.2% stated that they would be interested in music interventions. Patients especially conceived the relaxing and encouraging effects from listening to music. Most patients would prefer group therapies (56%) or listening to their own music (36.6%). CONCLUSION: Our data suggest that there is a need for music interventions in patients suffering from cancer in the head and neck, as they anticipate they would experience positive effects, including reduced somatic and non-somatic symptoms and improved QoL. The lack of homogenous data emphasizes the need for further trials in the field of complementary music interventions to establish science-based concepts in the future.

Augmented reality during parotid surgery: real-life evaluation of voice control of a head mounted display.

PURPOSE: Augmented Reality can improve surgical planning and performance in parotid surgery. For easier application we implemented a voice control manual for our augmented reality system. The aim of the study was to evaluate the feasibility of the voice control in real-life situations. METHODS: We used the HoloLens 1® (Microsoft Corporation) with a special speech recognition software for parotid surgery. The evaluation took place in a audiometry cubicle and during real surgical procedures. Voice commands were used to display various 3D structures of the patient with the HoloLens 1®. Commands had different variations (male/female, 65 dB SPL)/louder, various structures). RESULTS: In silence, 100% of commands were recognized. If the volume of the operation room (OR) background noise exceeds 42 dB, the recognition rate decreases significantly, and it drops below 40% at > 60 dB SPL. With constant speech volume at 65 dB SPL male speakers had a significant better recognition rate than female speakers (p = 0.046). Higher speech volumes can compensate this effect. The recognition rate depends on the type of background noise. Mixed OR noise (52 dB(A)) reduced the detection rate significantly compared to single suction noise at 52 dB(A) (p ≤ 0.00001). The recognition rate was significantly better in the OR than in the audio cubicle (p = 0.00013 both genders, 0.0086 female, and 0.0036 male). CONCLUSIONS: The recognition rate of voice commands can be enhanced by increasing the speech volume and by singularizing ambient noises. The detection rate depends on the loudness of the OR noise. Male voices are understood significantly better than female voices.

The effect of complementary music intervention on the patients' quality of life after septoplasty and rhinoplasty.

PURPOSE: Quality of life (QoL) assessment has emerged as an important evaluation tool for therapeutic treatments. The positive impact of complementary music interventions on QoL has been demonstrated in the literature, particularly in chronic and malignant diseases. However, its benefits during the perioperative period in head and neck patients have not been investigated thus far. METHODS: Head and neck patients undergoing septoplasty and rhinoplasty were prospectively randomized and consecutively included in the trial. Passive music intervention (60 min per day) was applied to the intervention group. QoL was assessed using the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire and the Functional Rhinoplasty Outcome Inventory 17 (FROI-17) questionnaire at three visits during the postoperative phase. Pain was measured using a visual analogue scale. RESULTS: Forty-four patients were enrolled in the study. The NOSE score between the control group and the intervention group in the septoplasty arm differed significantly at visit #2 (p < 0.001) and visit #3 (p < 0.015). For the rhinoplasty study arm, significant differences in the FROI-17 score were also found at visit #2 and visit #3 (p = 0.04). CONCLUSION: Complementary music interventions can considerably improve patients' QoL during the postoperative period. Furthermore, passive music interventions may be easily implemented in clinical practice as an additional cost-effective treatment with ubiquitous availability.

Targeted Treatment of HPV16-positive and -negative SCC Cells With Small Molecule Tyrosine Kinase Inhibitors and Everolimus Affects MMP2 and MMP14 Expression.

BACKGROUND/AIM: The rise of targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) has considerably widened the treatment range. Matrix metalloproteinases (MMPs) are key regulators of the tumor development of many cancer entities, which makes them a promising target for new treatment options. We examined the expression patterns of MMP2 and MMP14 in human papillomavirus (HPV)-positive and -negative SCC lines after treatment with small molecule tyrosine kinase inhibitors (TKIs) and a mechanistic target of rapamycin (mTOR) inhibitor in vitro. MATERIALS AND METHODS: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 µmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of MMP2 and MMP14 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those of untreated SCC cells. RESULTS: MMP2 and MMP14 were expressed in all three tested cell lines; expression levels were highest in the UMSCC-14C cell line. The tested TKIs significantly (p<0.05) reduced MMP2 expression in the UMSCC-14C cell line. In the HPV-positive cell line, the drugs led to an increase in MMP2 and MMP14 expression. CONCLUSION: Dysregulations in MMP signaling are involved in tumorigenesis and metastasis of HNSCCs; MMP2 has been noted as a potential biomarker. The expression of MMP2 and MMP14 is influenced effectively by small molecule TKIs and everolimus. Based on our data, future research should concentrate on a better understanding of the interplay between tumor microenvironment and tumor cells in vitro and in vivo.

[Professional teamwork and communication in the operating room-A narrative review]. / Professionelle Teamarbeit und Kommunikation im Operationssaal ­ Eine narrative Übersicht.

BACKGROUND: A team in the operating room (OR) is a hierarchically structured, gender-mixed group of people belonging to different professional categories. Disparities in the objectives of the different team members under economic pressure to perform, are sources of potential conflict in the daily work routine. This may have a negative impact on patient safety and commercial efficiency of hospital management. OBJECTIVE: The aim of this summary is to sensitize the reader to the complex of problems in daily life in the OR and to increase awareness of possible approaches to solve the difficulties in an OR. Problem solutions might be approached by improvement of communication and team building. METHODS: Narrative review of current literature and expert recommendations by a literature search in PubMed and Medline; keywords included teamwork, communication, operating room, team building. RESULTS AND CONCLUSION: Communication and teamwork in the OR are of immense importance for patient safety and the economic development of a hospital. Improvements in communication structure, among other things due to the implementation of a team time out and moderation from outside (OR manager) offer solutions to avoid conflicts in everyday clinical practice.

[Differential diagnosis of intraorbital masses - a narrative review]. / Differentialdiagnostik intraorbitaler Raumforderungen ­ eine Übersicht.

OBJECTIVE: Intraorbital masses represent a condition that is frequently threatening for the visual system. A rigorous differential diagnosis is essential to promptly initiate appropriate therapy and optimize prognosis. MATERIALS/METHODS: Narrative review of current literature and expert recommendations. For further illustration we describe the case of a 71-year-old male admitted to our department three months after sinus surgery. Postoperative intraorbital hematoma of the right orbit had been treated conservatively with antibiotics/corticosteroids, leading to a near-complete unilateral visual loss. The immediate surgical intervention aimed at decompression of the orbit and the optical nerve. Due to the delay, the intervention could not prevent formation of a lipogranuloma. Inflammatory phases associated with the lipogranuloma are successfully managed by conservative treatment based on multidisciplinary recommendations. RESULTS: In the case reported, delay of surgical therapy acted as a cause of intraorbital lipogranuloma formation. Literature supports our recommendation of immediate surgical intervention in case of acute retrobulbar hematoma. Besides acute conditions, intraorbital masses can be a sign of systemic disease. In every case, a multidisciplinary therapeutic approach is required for adequate management. CONCLUSIONS: Intraorbital masses can occur as a complication of trauma or e.g. sinus surgery. On the other hand they can be a sign of systemic disease. Timely diagnosis and treatment prevents from visual loss. That is why rigorous differential diagnosis is essential for every discipline managing intraorbital lesions.

[Surgical Management of Salivary Gland Carcinoma]. / Chirurgisches Vorgehen bei Speicheldrüsenkarzinomen.

Salivary gland carcinomas are very threatening diseases. The patient's survival depends to a large extent on planning and performing the resection. This article provides assistance with the most important surgical decisions. Using illustrative examples and practical tips the article shows how oncological salivary gland surgery can be successful.

Triple-Color STED Nanoscopy: Sampling Absorption Spectra Differences for Efficient Linear Species Unmixing.

Stimulated emission depletion (STED) in confocal fluorescence microscopy enables a visualization of biological structures within cells far below the optical diffraction limit. To meet the demand in the field for simultaneous investigations of multiple species within a cell, a couple of different STED techniques have been proposed, each with their own challenges. By systemically exploiting spectral differences in the absorption of fluorescent labels, we present a novel, beneficial approach to multispecies STED nanoscopy. By using three excitation wavelengths in nanosecond pulsed interleaved excitation (PIE) mode, we probe quasi simultaneously multiple species with fluorescent labels having absorption maxima as close as 13 nm. The acquired image is decomposed into its single species contributions by application of a linear unmixing algorithm based on present reference patterns. For multispecies images containing single species regions, we introduce the image correlation map (ICM). Here, the single species regions easily can be identified in order to generate the necessary single species reference patterns. This avoids the otherwise cumbersome and artifact prone preparation and recording of additional reference samples. The power of the proposed imaging scheme persists in species separation quality at high speed shown for up to three species with established reference samples and dyes commonly used for cellular STED imaging.

Nightly Hypoxia Does Not Seem to Lead to Otolith Dysfunction in Patients With Obstructive Sleep Apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) is a common sleep disorder, which is associated with recurrent oxygen desaturation during sleep. It has already been shown that nocturnal hypoxia may lead to cochlear dysfunction in patients with OSA. Less is known whether hypoxia during sleep also impacts vestibular function in those patients. Thus, the aim of the presented study was to assess a potential vestibulotoxic effect of nightly desaturations with hypoxia in patients with OSA by investigating a possible correlation between respiratory parameters and vestibular function tests. METHODS: A total of 56 patients were included in the study and underwent a fully attended cardiorespiratory polysomnography (PSG). Vestibular function was assessed using video head impulse test to evaluate horizontal semicircular canal function and cervical vestibular evoked myogenic potentials (cVEMPs) and ocular vestibular evoked myogenic potentials (oVEMPs) to measure otolith function. Descriptive data analysis was conducted and correlation analysis between selected PSG parameters and the results of vestibular testing was performed using Kendall τ coefficient. RESULTS: A significant correlation between vestibular function and respiratory polysomnographic parameters could not be demonstrated in the study (P > .05) but cVEMP and oVEMP results showed a trend toward a correlation with oxygen desaturation indices and apnea-hypopnea index. Additionally, otolith hypofunction was more prevalent in patients with hypertension as well as OSA. CONCLUSION: The results of our study show that there is no significant correlation between vestibular function and sleep apnea parameters, although otolith dysfunction might be more prevalent in patients with OSA and hypertension.

Maximum isometric tongue force in patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnea (OSA) is a sleep disorder with a prevalence of 9-38%. The underlying pathology in OSA is a collapse of the upper airway. Especially in more severely affected patients, this collapse is often located at the level of the tongue base. Therefore, various implantable systems (anchors and ligament techniques) were developed to prevent or overcome this collapse. These systems are exposed to various forces. Different models have been developed to measure these forces and data comparing forces in healthy individuals with OSA patients are rare. PURPOSE: Purpose of the study was to evaluate possible differences in tongue forces between healthy individuals and patients with OSA. METHOD: To evaluate maximum isometric tongue forces, we conducted a matched pair design study including 20 healthy individuals and 20 patients suffering from OSA. Maximum isometric tongue forces were measured in an anterior/posterior direction with the help of self-designed new device that clamps the tongue. RESULTS: We could show that the maximum isometric force does not differ significantly in healthy individuals (10.7 ± 5.2N) from patients with OSA (14.4 ± 6.3N). CONCLUSION: Currently there are no indications that maximum isometric tongue force does differ in healthy individuals and patients with OSA. Higher, as well as lower, tongue forces in patients with OSA seem not to differ from healthy subjects and therefore may not be needed to consider, in the development of tongue management devices, for OSA patients.

Cocaine Reduces Ciliary Beat Frequency of Human Nasal Epithelial Cells.

BACKGROUND/AIM: Cocaine is a widely used recreational drug and is known for its nasal complications including epithelial, cartilage and bone damage. The aim of the study was to analyze the impact of cocaine on ciliary beat frequency (CBF) of human nasal epithelial cells and therefore better understand its side effects on nasal mucosa. MATERIALS AND METHODS: Nasal epithelial cells of 21 healthy subjects were harvested and exposed in vitro to cocaine hydrochloride solutions ranging from 0.875% to 7%. High-speed video footage was acquired with phase contrast microscopy and CBF was analyzed with Sissons-Ammons Video Analysis (SAVA) software. RESULTS: All tested concentrations led to a significant reduction in CBF compared to the control. Effects increased over time and with concentration. A mechanical inhibition of cilia by cocaine crystals was also observed. CONCLUSION: We assume that CBF reduction is part of the pathomechanism leading to nasal complications in cocaine abuse. Considering these results, clinical usage of cocaine should be critically evaluated and restricted to select cases only.

Apoptosis-related Proteins Are Altered by Selective Tyrosine Kinase Inhibitors and Everolimus in HPV-dependent SCC.

BACKGROUND: Head and neck squamous cell cancer (HNSCC) affects the oral cavity and the pharynx. The aim of the study was to investigate the effects of selective tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib, nilotinib and dasatinib and the mammalian target of rapamycin (mTOR) inhibitor everolimus on the expression of apoptosis-related proteins caspase-3, FAS cluster of differentiation (CD)-95 and FAS ligand in human papilloma virus (HPV)-dependent squamous cancer. MATERIALS AND METHODS: Two HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with TKIs or everolimus and protein concentrations of target proteins were analyzed with enzyme-linked immunosorbent assay (ELISA). RESULTS: Caspase-3 was affected by the tested TKIs in HPV-positive SCC, whereas FAS CD95 and FAS ligand were influenced in HPV-negative SCC. DISCUSSION: This is the first study to analyze the influence of TKIs and everolimus on key proteins of apoptosis. Our results provide novel information contributing to a better understanding of the cell biology of HPV-dependent HNSCC and might contribute to the discovery of novel pharmaceutical treatment strategies for HNSCC.

FGF Expression in HPV16-positive and -negative SCC After Treatment With Small-molecule Tyrosine Kinase Inhibitors and Everolimus.

BACKGROUND: Targeted therapies in the treatment of head and neck squamous cell carcinoma (HNSCC) are subject to extensive research. Different mutations of genes belonging to the fibroblast growth factor (FGF) family have been detected in HNSCC. In this study, we examined the expression of FGF1 and FGF2 after treatment with small-molecule tyrosine kinase inhibitors (TKIs) and an inhibitor of mechanistic target of rapamycin (mTOR) in vitro using human papillomavirus (HPV)-positive and -negative SCC lines. MATERIALS AND METHODS: Cells of two human HPV-negative cell lines (UMSCC-11A/-14C) and one HPV-positive cell line (CERV196) were incubated with 20 µmol/l of erlotinib, gefitinib, nilotinib, dasatinib, or everolimus for 24-96 h. Cell proliferation was assessed by proliferation assay and the protein concentrations of FGF1 and FGF2 by sandwich enzyme-linked immunosorbent assay. For statistical analysis, the results were compared with those for untreated HPV-negative SCC cells. RESULTS: FGF1 and FGF2 were detected in all three tested cell lines. The tested TKIs significantly (p<0.05 reduced) FGF1 expression in the UMSCC-11A cell line within the first 24 h. At later time points, the tested TKIs and everolimus significantly (p<0.05) increased FGF1 and FGF2 expression in HPV-negative and -positive cancer cell lines. The effect was stronger in the HPV-positive cell line. CONCLUSION: Alterations in FGF signalling are considered to be relevant drivers of tumourigenesis in some HNSCCs. Our results show that the expression of FGF1 and -2 can be influenced effectively by small-molecule TKIs and everolimus. Based on our data, future research should include combinations of specific FGF inhibitors, mTOR inhibitors and other TKIs in the treatment of HNSCC and research on FGF-mediated drug escape mechanisms.