An unusual clinical presentation of a plunging ranula-The plunging ranula with extension to the vallecula.

Key Clinical Message: A plunging ranula may present initially as an extensive vallecular cyst and correct diagnosis may be reached with the use of ultrasound, fluid aspiration for amylase detection, and MRI imaging. Abstract: The ranula is a pseudocyst of the sublingual salivary gland and can be divided into two known subtypes. The simple ranula and plunging ranula. While the simple type can be found in the floor of the mouth, the plunging ranula usually pervades the mylohoid muscle and presents as a cervical swelling. The presented case should outline the difficulties in diagnostic and treatment of an uncommon expression of a mucocele above the mylohoid muscle without presenting either a cervical or an intraoral swelling, only extending towards the vallecula. We present a previously unreported clinical manifestation of a ranula of an 18-year old male, which extends posteriorly, remaining confined in the supramylohyoid muscle space. The cystic lesion protrudes in the oropharynx, and clinically appears as an extensive vallecular cyst. On magnetic resonance imaging the initial suspected diagnosis of a vallecular cyst was changed to the final diagnosis of a plunging ranula. The marsupialization of the cyst sac was performed. Outpatient follow-up revealed a persisting ostium, indicating a continuous extravasation of the sublingual gland. The present case report describes an unusual clinical presentation of a plunging ranula, remaining above the mylohyoid muscle and protruding into the oropharynx, misdirecting to the first suspected diagnosis of a vallecular cyst. The case highlights the useful contribution of the MRI imaging for differential diagnoses and the need for criteria to indicate further investigations.

The "fascia taco" for nasal septum perforation closure-A retrospective Cohort study on success rates and patient reported outcomes.

Objective: Nasal septum perforation (NSP) is a common condition affecting ~1.2% of the general population and is still considered challenging to treat. Therapeutic strategies range from conservative local treatments and septal button closures to over 40 different surgical approaches. This study aimed to present a novel secure approach. Methods: We describe our novel and unique NSP closure approach using a "fascia taco," in which conchal cartilage is enveloped by temporalis fascia like a taco and splints are left in place for 6-8 weeks. A review of patient charts was conducted and questionnaires including the German-SNOT-22 and D-NOSE were sent by mail to all eligible patients who received a fascia taco between 2016 and 2021. Results: Thirty-three patients were identified. The questionnaire response rate was 54.5%. The mean operative time (cut to sew) for all patients who only underwent NSP closure was 90.4 min. The overall success rate in terms of postoperative NSP closure was 81.8%. We found an apparent but nonsignificant association between closure failure and smoking (failure rate 66.6% in smokers vs. 15.4% in nonsmokers; X 2 = 3.4188, p = .064). Questionnaire analysis showed a significant postoperative reduction of mean values in D-NOSE from 60.8 to 33.1 (p = .009) and in German-SNOT-22 from 38.6 to 21.2 (p = .005). Conclusion: The fascia taco technique is an easy-to-apply, safe procedure for NSP closure that is short in duration and associated with a low morbidity, resulting in excellent patient satisfaction. Level of Evidence: 4.

[How much digitization do ENT curricula need? : Opportunities and limits from the perspective of students and teachers]. / Wieviel Digitalisierung braucht die HNO-Lehre? : Chancen und Grenzen aus Sicht von Studierenden und Lehrenden.

BACKGROUND: Digitalization has long been an integral part of students' everyday lives and increasingly also of their medical training. It seems to be an unwritten law that "digital natives" want as much digitalization as possible. This study aims to shed more light on how students in the clinical phase of medical studies perceive the increasing digitalization of teaching and what they need for good education. MATERIALS AND METHODS: This study analyzed two surveys that were conducted using an online questionnaire. On the one hand, students in the 5th-9th semesters of the medical faculty at the University of Hamburg (n = 282) were surveyed (survey 1). Another survey addressed all employees of ENT clinics in Germany (n = 175; survey 2). RESULTS: A total of 76 students took part in survey 1 and 123 lecturers in survey 2. The results show that both students and lecturers do not want face-to-face teaching to be completely replaced by digital formats. A total of 72.7% of students reject the possibility of teaching practical skills through digital formats. The majority of students surveyed stated that offline formats improve their concentration (61.1%), participation probability (63.9%), and motivation to learn (76.6%). In contrast, 40.2% of lecturers see digitalization as a way to reduce the workload without any relevant loss in teaching quality. CONCLUSION: Digital teaching formats have a negative impact on the medical education of the students surveyed. Interaction and physical presence are needed to increase the motivation to learn. This leads to the first conclusion that students are critical of the increasing digitalization of medical studies.

Pre-clinical evaluation of APrevent® VOIS for unilateral vocal fold paralysis medialization.

Objective: To evaluate the concept and efficacy of an adjustable implant (Prototype SH30: porcine implant and APrevent® VOIS: human concept) for treatment of unilateral vocal fold paralysis (UVFP) via in vivo mini-pig studies, human computed tomographic (CT) and magnetic resonance (MR) image analysis, ex-vivo aerodynamic and acoustic analysis. Methods: Feasibility testing and prototype implantation were performed using in-vivo UVFP porcine model (n = 8), followed by a dimensional finding study using CT and MR scans of larynges (n = 75) for modification of the implant prototypes. Acoustic and aerodynamic measurements were recorded on excised canine (n = 7) larynges with simulated UVFP before and after medialization with VOIS-Implant. Results: The prototype showed in the in-vivo UVFP porcine model an improved glottic closure from grade 6 incomplete closure to complete closure (n = 5), to grade 2 incomplete closure (n = 2) and grade 3 incomplete closure (n = 1). On human CT/MR scans the identification of the correct size was successful in 97.3% using the thyroid cartilage alar "distance S" as the only parameter, which is an important step towards procedure standardization and implant design. Results were confirmed with implantation in human laryngeal cadavers (n = 44). Measurements of the acoustic and aerodynamic effects after implantation showed a significant decreased phonation threshold pressure (p = .0187), phonation threshold flow (p = .0001) and phonation threshold power (p = .0046) on excised canine larynges with simulated UVFP. Percent jitter and percent shimmer decreased (p = .2976; p = .1771) but not significant. Conclusions: Based on the preclinical results four sizes, differing in medial length, implant width and expansion direction of silicone cushions, seem to be enough to satisfy laryngeal size variations. This concept is significantly effective in medializing UVFP and improving the aerodynamic and acoustic qualities of phonation as reported in a preliminary clinical outcome study with long-term implantation. Level of Evidence: N/A.

Outcomes following oropharyngeal squamous cell carcinoma resection and bilateral neck dissection with or without contralateral postoperative radiotherapy of the pathologically node-negative neck.

PURPOSE: There are no consensus guidelines regarding the postoperative treatment of the contralateral pathologically node-negative neck in oropharyngeal squamous cell carcinoma. This study aimed to determine if omission of postoperative irradiation of the contralateral pathologically node-negative neck affects oncological outcomes. METHODS: We retrospectively identified 84 patients with primary surgical treatment including bilateral neck dissection and postoperative (chemo-)radiotherapy (PO(C)RT). Survival was analyzed using the log-rank test and the Kaplan-Meier method. RESULTS: Patients showed no decrease in tumor-free, cause-specific (CSS), or overall survival (OS) when PO(C)RT of the contralateral pathologically node-negative neck was omitted. Increased OS was found in patients with unilateral PO(C)RT and especially an increased OS and CSS was found in unilateral PO(C)RT and in tumors arising from lymphoepithelial tissue. CONCLUSIONS: Omitting the contralateral pathologically node-negative neck appears to be safe in terms of survival and our retrospective study advocates further prospective randomized control de-escalation trials.

Lipidome Analysis of Oropharyngeal Tumor Tissues Using Nanosecond Infrared Laser (NIRL) Tissue Sampling and Subsequent Mass Spectrometry.

Ultrashort pulse infrared lasers can simultaneously sample and homogenize biological tissue using desorption by impulsive vibrational excitation (DIVE). With growing attention on alterations in lipid metabolism in malignant disease, mass spectrometry (MS)-based lipidomic analysis has become an emerging topic in cancer research. In this pilot study, we investigated the feasibility of tissue sampling with a nanosecond infrared laser (NIRL) for the subsequent lipidomic analysis of oropharyngeal tissues, and its potential to discriminate oropharyngeal squamous cell carcinoma (OPSCC) from non-tumorous oropharyngeal tissue. Eleven fresh frozen oropharyngeal tissue samples were ablated. The produced aerosols were collected by a glass fiber filter, and the lipidomes were analyzed with mass spectrometry. Data was evaluated by principal component analysis and Welch's t-tests. Lipid profiles comprised 13 lipid classes and up to 755 lipid species. We found significant inter- and intrapatient alterations in lipid profiles for tumor and non-tumor samples (p-value < 0.05, two-fold difference). Thus, NIRL tissue sampling with consecutive MS lipidomic analysis is a feasible and promising approach for the differentiation of OPSCC and non-tumorous oropharyngeal tissue and may provide new insights into lipid composition alterations in OPSCC.

Impaired DNA double-strand break repair and effective radiosensitization of HPV-negative HNSCC cell lines through combined inhibition of PARP and Wee1.

Objectives: In head and neck squamous cell carcinoma (HNSCC), tumors negative for Human Papillomavirus (HPV) remain a difficult to treat entity and the morbidity of current multimodal treatment is high. Radiotherapy in combination with molecular targeting could represent suitable, less toxic treatment options especially for cisplatin ineligible patients. Therefore, we tested dual targeting of PARP and the intra-S/G2 checkpoint through Wee1 inhibition for its radiosensitizing capacity in radioresistant HPV-negative HNSCC cells. Materials and methods: Three radioresistant HPV-negative cell lines (HSC4, SAS, UT-SCC-60a) were treated with olaparib, adavosertib and ionizing irradiation. The impact on cell cycle, G2 arrest and replication stress was assessed through flow cytometry after DAPI, phospho-histone H3 and γH2AX staining. Long term cell survival after treatment was determined through colony formation assay and DNA double-strand break (DSB) levels were assessed through quantification of nuclear 53BP1 foci in cell lines and patient-derived HPV± tumor slice cultures. Results: Wee1 and dual targeting induced replication stress but failed to effectively inhibit radiation-induced G2 cell cycle arrest. Single as well as combined inhibition increased radiation sensitivity and residual DSB levels, with the largest effects induced through dual targeting. Dual targeting also enhanced residual DSB levels in patient-derived slice cultures from HPV-negative but not HPV+ HNSCC (5/7 vs. 1/6). Conclusion: We conclude that the combined inhibition of PARP and Wee1 results in enhanced residual DNA damage levels after irradiation and effectively sensitizes radioresistant HPV-negative HNSCC cells. Ex vivo tumor slice cultures may predict the response of individual patients with HPV-negative HNSCC to this dual targeting approach.

An Accessory Muscle Originating From the Hyoid Bone and Inserting Into the Sternocleidomastoid Muscle.

Irregular bellies and insertions into neck muscles have been described in the literature. To the best of our knowledge, a right accessory muscle originating from the hyoid bone and inserting into the sternocleidomastoid muscle has not been reported to date. Here, we report the case of a 72-year-old male patient with an irregular muscle originating from the lesser horn of the hyoid bone and inserting into sternocleidomastoid muscle fibers.

Hereditary head and neck paraganglioma: from basics to practical consequences.

PURPOSE OF REVIEW: This review summarizes practical recommendations for screening, work-up, and management of hereditary head and neck paragangliomas based on the growing molecular and empirical understanding of this disease. RECENT FINDINGS: The proportion of hereditary cases among head and neck paragangliomas is significant (∼33 to 50%), and specific genetic alterations may increase the risk of malignancy. Genotyping should be performed for each case, and patients carrying a pathological mutation should be regularly screened for new tumors. Computed tomography (CT), magnetic resonance imaging (MRI), digital subtraction angiography (DSA), and functional positron emission tomography (PET) can provide a reliable preoperative diagnosis in the absence of histology. Comparative data on therapeutic outcome and morbidity now render radiation, stereotactic radiosurgery, and active surveillance preferable over surgery in highly advanced cases of jugulotympanic and vagal paragangliomas, whereas surgery remains the first choice for most carotid body paragangliomas. SUMMARY: Complete paraganglioma removal continues to be the primary therapeutic goal; however, this is sometimes impossible to accomplish with acceptable morbidity. In these cases, therapy selection should focus on preserving cranial nerve function and minimizing both tumor-associated and therapy-associated complications, particularly in genetically predisposed patients. An interdisciplinary approach to the management of hereditary head and neck paragangliomas is strongly recommended.

Nasoseptal Flap for Skull Base Reconstruction in a Three-Year-Old Child With Nasofrontal Meningoencephalocele.

Congenital anterior skull base defects with meningoencephaloceles causing nasal obstruction and cerebrospinal fluid (CSF) rhinorrhea are rare clinical entities. Traditionally, skull base defects have been repaired via a bifrontal craniotomy. With the introduction of pediatric endoscopic instrumentation, more of these lesions are accessible via an intranasal endoscopic approach, even in the infant population. However, due to the rarity of pediatric meningoencephaloceles, there is a lack of data demonstrating the successful adaptation of endoscopic skull base techniques to the pediatric population. In this report, we present a case of a pediatric frontonasal meningoencephalocele with an anterior skull base defect in a 3-year-old child that was successfully addressed transnasally following 4 failed transcranial approaches. The case highlights the importance of a thorough preoperative evaluation of the surgical approach as well as interdisciplinary management of these patients at a young age. Congenital anterior skull base defects with meningoencephaloceles and CSF leaks are rare clinical entities. Hence, an interdisciplinary approach is vital including experienced pediatricians, otolaryngologists, and neurosurgeons to evaluate the ideal surgical method on an individual basis. The transnasal endoscopic technique has been shown to be minimally invasive, efficient, and safe to apply even to the infant population which could positively be demonstrated in this case.

[Comments on the term "drainage"]. / Anmerkungen zum Terminus "Drainage".

BACKGROUND: Use of the term "drainage" is inconsistent in clinical practice and the existing literature. OBJECTIVE: The aim of this study was to clarify the meaning of the term and to raise awareness of its proper use. MATERIALS AND METHODS: A selective literature search was performed. RESULTS: Drainage is the process of removing fluid but the term is often used interchangeably with the drain tube, which is often inserted at the same time, which is linguistically referred to as a metonymy. A tympanostomy tube is used for middle ear ventilation and pressure equalization. Lymphatic and abscess drainage are not objects. CONCLUSION: Standardized technical terminology serves to prevent vagueness and consecutive misunderstandings in a scientific context. This is particularly important in medicine, but is subject to a certain variability in everyday language use.

Is Vestibular Neuropathy Rather a Neuritis?

Background/objectives Vestibular neuritis (VN) is one of the most common causes of peripheral vestibular neuropathy. The goal of this study is to investigate the possible infectious causes of VN in a large cohort of patients. Material and methods In total, 98 consecutive VN patients were enrolled in this retrospective study over a four-year period (04/2015-04/2019). Diagnosis of VN was made by clinical examination and functional diagnostics. We focused on infectious causes such as neurotropic viruses and Lyme disease (LD) and evaluated infection parameters as well as the concomitant diseases. Results In this cohort, we found pathologically elevated leukocytes or C-reactive protein (CRP) levels, and/or acute herpes simplex virus (HSV) infection, cytomegalovirus (CMV) infection and LD in 42 patients (42.85%). Leukocytes were elevated in 39 of 98 patients (39.8%) and the mean count was 9717 ± 2991 /µl. The group comparison between patients with vestibular loss (n=42) and patients with vestibular hypofunction (n=45) revealed a significant difference in regard to elevated leukocytes (p=0.028). In total, 28 of 53 patients (52.8%) were positive for HSV immunoglobulin (Ig) G and four of 53 patients were positive for HSV IgM (7.5%). Six of 53 patients (11.3%) were positive for LD IgM. Conclusion In this cohort, there was a large number of VN patients with infectious signs; several patients tested positive for HSV and LD. Therefore we recommend testing VN patients not only for HSV but also for LD and other neurotropic viruses. This approach enables to complement the standard VN treatment with a specific treatment.

A Four-Generational Report on Hereditary Head and Neck Paraganglioma.

Background This article investigates the inheritance, penetrance, clinical presentation, and therapeutic outcomes of hereditary head and neck paragangliomas (HNPGLs) by offering a four-generational report of an 18-member family affected by this rare condition. Methodology Information was compiled by examination of patients and a review of medical records and correspondence (retrospective case series). Results Six members of the 18-member family were diagnosed with HNPGL between 2002 and 2018. A known pathogenic point mutation in subunit D of the succinyl dehydrogenase complex (SDHD, c.317G>T, p.Gly106Val) was responsible for the tumor phenotype. The mutation could be revealed in seven family members, three diseased adults, one healthy adult, and three healthy children, out of the nine who consented to gene testing. The median age at diagnosis was 33.5 years (range: 22-50 years). Five of the eight primary tumors were glomus caroticum, two were glomus jugulare, and one was a glomus vagale tumor. The therapeutic approaches were multimodal and included embolization therapy, surgery, radiation, and watchful waiting. Follow-up was reported for five of the six patients (mean follow-up of 34.8 months after primary therapy); three showed no disease progression or recurrence. Conclusions This study exemplifies the autosomal dominant, parent-of-origin-dependent inheritance and the high disease penetrance in hereditary paraganglioma-pheochromocytoma syndromes. Six out of a total of eight adult descendants (75%) of the original SDHD mutation carrier developed tumors, and the morbidity associated with the disease as well as its therapy was especially high in late-diagnosed, advanced cases. This substantiates the necessity for early radiologic surveillance and genetic testing.

Patient derived ex vivo tissue slice cultures demonstrate a profound DNA double-strand break repair defect in HPV-positive oropharyngeal head and neck cancer.

BACKGROUND: HPV-positive head and neck squamous cell carcinoma of the oropharynx (OPSCC) are more sensitive towards radiation than HPV-negative OPSCC. Two main theories exist regarding the underlying mechanism. Stronger lymphocyte infiltration points to an enhanced immunogenicity, whereas data from HPV-positive HNSCC cell lines suggest an enhanced cellular radiosensitivity based on a defect in DNA double-strand break (DSB) repair. The critical limitation of the latter theory is that the evidence was largely derived from a small number of established HPV-positive HNSCC cell lines. METHODS AND MATERIALS: Fresh patient-derived OPSCC samples were cut in 400 µm sections and cultured on cell culture inserts. Slice cultures were irradiated, in part combined with ATM inhibition, and fixed and frozen after 2 and 24 h. DSBs were analyzed by quantification of 53BP1 foci in nuclei co-stained with the SCC marker p63 via immunofluorescence microscopy. RESULTS: Ex vivo OPSCC tumor slice cultures maintained stable oxygenation and proliferation characteristics for at least 3 days. Areas of p63-positivity in immunofluorescence microscopy matched histologically confirmed tumor cell areas in serial sections, indicating the suitability of p63 as a tumor cell marker. p63-positive nuclei in HPV-positive OPSCC tissues (n = 14) showed profoundly elevated numbers of residual radiation-induced DSBs as compared to those from HPV-negative OPSCC (n = 12) (3 Gy: on average 4.9 vs. 1.2 foci per nucleus; p < 0.0001). Within the HPV-positive subgroup, samples derived from patients with a smoking history of less than 10 pack years demonstrated higher residual DSBs as compared to those derived from patients with 10 or more pack years (3 Gy: on average 6.5 vs. 3.2 foci per nucleus; p = 0.0105). Additional ATM inhibition resulted in a substantial increase in residual foci in all 4 HPV-negative samples tested but strikingly only in 2 out of 11 HPV-positive samples. CONCLUSIONS: In summary, our data provide robust, cell line-independent experimental evidence for an intrinsic DSB repair deficiency in HPV-positive OPSCC, strongly suggesting a meaningful contribution to the enhanced clinical radiosensitivity. The reduced effectiveness of ATM inhibition indicates a defect in the ATM-orchestrated DNA damage response. Lower numbers of residual 53BP1 nuclear foci in the ex vivo assay may identify HPV-positive patients with effective DSB repair who should potentially be excluded from de-intensification approaches.

Laryngeal Manifestation of Nodular Fasciitis: A Case Report and Literature Review.

Nodular fasciitis (NF) are non-neoplastic, fibroblastic lesions, typically located on the trunk and the extremities. The incidence of NF in the head and neck region is 13%-20%. However, a manifestation in the larynx of adult patients is extremely rare. Therefore, the occurrence of NF in this region can lead to diagnostic challenges and a high risk of misdiagnosis as well as potential mishandling when not aware of its possible laryngeal manifestation. Following emergency admission of a 41-year-old woman to the emergency department (ED) due to progressive dyspnea and inspiratory stridor a transnasal flexible laryngeal endoscopic examination revealed a left-lateral, subglottic mass. A subsequently performed CT demonstrated a 2.2 cm x 1.5 cm sized lesion of the subglottic larynx with profound stenosis of the lumen (Myer-Cotton grade III), no extraluminal extension, and no distant metastases. Histopathological processing of a tissue sample obtained by microlaryngoscopy and translaryngeal tracheoscopy revealed a spindle-cell lesion with immunohistochemical and molecular-pathogenic profile of NF. After tumor debulking and steroid infiltration (triamcinolone), a regrowth tendency quickly became apparent, which is why a tracheostomy had to be performed. Laryngectomy was rejected by the patient. After multiple transoral tumor reduction attempts, radiotherapy was performed according to an interdisciplinary tumor board decision to limit regrowth tendency. Subsequently, a substantial reduction of the tumor volume could be seen, although a discreet stenosis of the subglottic tracheal lumen persists in the follow-up. Laryngeal NF poses several challenges due to its rare occurrence in this location. This case report emphasizes the knowledge of this differential diagnosis and also depicts an interdisciplinary therapeutic approach aiming for function-preserving treatment of this benign but potentially relapsing pathology.

Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src family kinases as prognostic markers and potential targets.

Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients. Here we present a systematic analysis of the tyrosine kinases in head and neck cancer using such a test-functional kinome profiling. We detected increased tyrosine kinase activity in tumors compared with their corresponding normal tissue. Moreover, we identified members of the family of Src kinases (Src family kinases [SFK]) to be aberrantly activated in the majority of the tumors, which was confirmed by additional methods. We could also show that SFK hyperphosphorylation is associated with poor prognosis, while inhibition of SFK impaired cell proliferation, especially in cells with hyperactive SFK. In summary, functional kinome profiling identified SFK to be frequently hyperactivated in head and neck squamous cell carcinoma. SFK may therefore be potential therapeutic targets. These results furthermore demonstrate how functional tests help to increase our understanding of cancer biology and support the expansion of precision oncology.

Rational surgical neck management in total laryngectomy for advanced stage laryngeal squamous cell carcinomas.

PURPOSE: Controversies exist in regard to surgical neck management in total laryngectomies (TL). International guidelines do not sufficiently discriminate neck sides and sublevels, or minimal neck-dissection nodal yield (NY). METHODS: Thirty-seven consecutive primary TL cases from 2009 to 2019 were retrospectively analyzed in terms of local tumor growth using a previously established imaging scheme, metastatic neck involvement, and NY impact on survival. RESULTS: There was no case of level IIB involvement on any side. For type A and B tumor midline involvement, no positive contralateral lymph nodes were found. Craniocaudal tumor extension correlated with contralateral neck involvement (OR: 1.098, p = 0.0493) and showed increased involvement when extending 33 mm (p = 0.0134). Using a bilateral NY of ≥ 24 for 5-year overall survival (OS) and ≥ 26 for 5-year disease-free survival (DFS) gave significantly increased rate advantages of 64 and 56%, respectively (both p < 0.0001). CONCLUSIONS: This work sheds light on regional metastatic distribution pattern and its influence on TL cases. An NY of n ≥ 26 can be considered a desirable benchmark for bilateral selective neck dissections as it leads to improved OS and DFS. Therefore, an omission of distinct neck levels cannot be promoted at this time.

Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).

BACKGROUND: For loco-regionally advanced, but transorally resectable oropharyngeal cancer (OPSCC), the current standard of care includes surgical resection and risk-adapted adjuvant (chemo) radiotherapy, or definite chemoradiation with or without salvage surgery. While transoral surgery for OPSCC has increased over the last decade for example in the United States due to transoral robotic surgery, this treatment approach has a long history in Germany. In contrast to Anglo-Saxon countries, transoral surgical approaches have been used frequently in Germany to treat patients with oro-, hypopharyngeal and laryngeal cancer. Transoral laser microsurgery (TLM) has had a long tradition since its introduction in the early 70s. To date, the different therapeutic approaches to transorally resectable OPSCC have not been directly compared to each other in a randomized trial concerning disease control and survival. The goal of this study is to compare initial transoral surgery to definitive chemoradiation for resectable OPSCC, especially with regards to local and regional control. METHODS: TopROC is a prospective, two-arm, open label, multicenter, randomized, and controlled comparative effectiveness study. Eligible patients are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 UICC vers. 7) which are amenable to transoral resection. Two hundred eighty patients will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be performed according to daily routine practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant therapy. Patients treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits for 3 years are planned. Primary endpoint is time to local or locoregional failure (LRF). Secondary endpoints include overall and disease free survival, toxicity, and patient reported outcomes. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a scientific support program. DISCUSSION: This study will shed light on an urgently-needed randomized comparison of the strategy of primary chemoradiation vs. primary surgical approach. As a comparative effectiveness trial, it is designed to provide data based on two established regimens in daily clinical routine. TRIAL REGISTRATION: NCT03691441 Registered 1 October 2018 - Retrospectively registered.