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Introduction, aim: Extraesophageal reflux (EER) is the backflow of gastric fluids (most often acidic) above the level of the upper esophageal sphincter (it differs from gastroesophageal reflux). The symptoms of extraesophageal reflux are non-specific, of varying intensity and depend on the location of the pathological action of the refluxate. In the case of the effect of refluxate on the hard dental tissue, EER can contribute to the formation of dental erosions. In addition to refluxate, other factors such as the composition of saliva and the microbiome of the oral cavity are discussed. In recent years, there has been a significant shift in the understanding of extraesophageal reflux, especially the pathogenesis, and the resulting implications for diagnosis and treatment. The aim of the article is to inform about EER and give an overview of the current possibilities of diagnosis and its treatment, as well as to summarize the results of recent meta-analyses regarding the role of EER in the development of dental diseases.Methods: The basis for the presented article was professional publications obtained in the PubMed, Cochrane Library and Scopus databases from 2002 to 2022. Publications were searched using a combination of keywords in English and Czech languages: extraesophageal reflux, gastroesophageal reflux, dental erosion. A total of 21 studies discussing the association between reflux and dental erosions were analyzed through review, clinical prospective and retrospective studies and meta analyses. The included studies were conducted in the adult population and information on gastroesophageal reflux in relation to the occurrence of dental erosions was used only if it was diagnosed by multichannel intraluminal pH impedance monitoring. The first part of the article presents a current view of the pathophysiology, diagnosis and treatment of EER. The second part summarizes knowledge about dental erosions. In the third part, studies dealing with the effect of EER on dental erosion are presented.Results: The obtained information indicates a higher prevalence of dental erosions in patients with EER compared to the healthy population. The reason is that acids of both exogenous and endogenous origins play an important role in dissolving enamel minerals, which ultimately leads to tooth erosion. Based on the analyzed studies, the relationship between reflux and the development of dental erosions cannot currently be considered causal, mainly due to the low quality of the studies. The authors recommend that further studies investigating the relationship between EER and dental damage should be conducted.Conclusions: Based on the findings, it can be assumed that extraesophageal reflux is involved in the development of dental diseases. A possible link is also supported by the fact that the prevalence of dental erosions in population with reflux or the prevalence of reflux in the population with dental erosions is much higher compared to the healthy population. In the future, however, further studies are needed to investigate the causality of extraesophageal reflux in the occurrence of dental erosions.

Squamous cell carcinoma (SCC) of the head and neck originates from the mucosal lining of the upper aerodigestive tract, including the lip, tongue, nasopharynx, oropharynx, larynx and hypopharynx. In this review, we summarise what is currently known about the potential function of primary cilia in the pathogenesis of this disease. As primary cilia represent a key cellular structure for signal transduction and are related to cell proliferation, an understanding of their role in carcinogenesis is necessary for the design of new treatment approaches. Here, we introduce cilia-related signalling in head and neck squamous cell carcinoma (HNSCC) and its possible association with HNSCC tumorigenesis. From this point of view, PDGF, EGF, Wnt and Hh signalling are discussed as all these pathways were found to be dysregulated in HNSCC. Moreover, we review the clinical potential of small molecules affecting primary cilia signalling to target squamous cell carcinoma of the head and neck area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Putnová, Putnová, Hurník, Štembírek, Buchtová and Kolísková.)

Introduction: In the era of personalized medicine and treatment optimization, use of immune biomarkers holds promise for estimating the prognosis of patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive treatment., Methods: To evaluate the prognostic potential of immune biomarkers, we conducted a prospective monocentric cohort study with loco-regionally advanced HNSCC patients indicated for definitive radiotherapy/radiochemotherapy at the Department of Oncology, Ostrava University Hospital, Czech Republic, between June 2020 and August 2023. We focused on the expression of programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) relative to overall survival (OS) and specific survival rates. Associations between biomarkers and survival rates were assessed by crude and adjusted hazard ratios (cHR, aHR, respectively) obtained from Cox proportional hazards regression., Results: Among a total of 55 patients within a median follow-up of 19.7 months, there were 21 (38.2%) all-cause deaths and 15 (27.3%) cancer-related deaths. An overall survival (OS) rate of 61.8% and a disease-specific survival (DSS) rate of 72.7% were recorded. A significant association between survival rates and a ≥10% difference in PD-L1 expression on immune versus tumor cells (high PD-L1 IC expression) was documented regardless of the type of analysis (univariate or multivariate). In addition, a stronger association was confirmed for OS and the composite biomarker high PD-L1 IC expression along with either median-higher CD8+ TIL count or increased TIL density ≥30%, as indicated by an aHR of 0.08 (95% CI, 0.01 to 0.52) and 0.07 (95% CI, 0.01 to 0.46), respectively. Similar results were demonstrated for other specific survival rates., Discussion: The early outcomes of the present study suggest the utility of a strong prognostic factor involving a composite biomarker high PD-L1 IC expression along with increased TIL density in HNSCC patients undergoing definitive radiotherapy and radiochemotherapy., Trial Registration: The study is registered with Clinicaltrials.gov. - NCT05941676., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Blažek, Petráš, Hurník, Matoušek, Knybel, Čermáková, Štembírek, Cvek and Soumarová.)

Objective: Oral squamous cell carcinoma (OSCC) originates from the mucosal lining of the oral cavity. Almost half of newly diagnosed cases are classified as advanced stage IV disease, which makes resection difficult. In this study, we investigated the pathological features and mutation profiles of tumor margins in OSCC., Methods: We performed hierarchical clustering of principal components to identify distinct patterns of tumor growth and their association with patient prognosis. We also used next-generation sequencing to analyze somatic mutations in tumor and marginal tissue samples., Results: Our analyses uncovered that the grade of worst pattern of invasion (WPOI) is strongly associated with depth of invasion and patient survival in multivariable analysis. Mutations were primarily detected in the DNA isolated from tumors, but several mutations were also identified in marginal tissue. In total, we uncovered 29 mutated genes, mainly tumor suppressor genes involved in DNA repair including BRCA genes; however none of these mutations significantly correlated with a higher chance of relapse in our medium-size cohort. Some resection margins that appeared histologically normal harbored tumorigenic mutations in TP53 and CDKN2A genes., Conclusion: Even histologically normal margins may contain molecular alterations that are not detectable by conventional histopathological methods, but NCCN classification system still outperforms other methods in the prediction of the probability of disease relapse., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hurník, Režnarová, Chyra, Motyka, Putnová, Čermáková, Blažek, Fománek, Gaykalova, Buchtová, Ševčíková and Štembírek.)

Background: Ameloblastic carcinoma and metastasising ameloblastoma are rare epithelial odontogenic tumours with aggressive features. Distinguishing between these two lesions is often clinically difficult but necessary to predict tumour behaviour or to plan future therapy. Here, we provide a brief review of the literature available on these two types of lesions and present a new case report of a young man with an ameloblastoma displaying metastatic features. We also use this case to illustrate the similarities and differences between these two types of tumours and the difficulties of their differential diagnosis., Case Presentation: Our histopathological analyses uncovered a metastasising tumour with features of ameloblastic carcinoma, which developed from the ameloblastoma. We profiled the gene expression of Wnt pathway members in ameloblastoma sample of this patient, because multiple molecules of this pathway are involved in the establishing of cell polarity, cell migration or for epithelial-mesenchymal transition during tumour metastasis to evaluate features of tumor behaviour. Indeed, we found upregulation of several cell migration-related genes in our patient. Moreover, we uncovered somatic mutation BRAF p.V600E with known pathological role in cancerogenesis and germline heterozygous FANCA p.S858R mutation, whose interpretation in this context has not been discussed yet., Conclusions: In conclusion, we have uncovered a unique case of ameloblastic carcinoma associated with an alteration of Wnt signalling and the presence of BRAF mutation. Development of harmful state of our patient might be also supported by the germline mutation in one FANCA allele, however this has to be confirmed by further analyses., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The incidence of advanced oral cavity and oropharyngeal cancers is generally high. Treatment outcomes for patients, especially those unfit for comprehensive cancer treatment, are unsatisfactory. Therefore, the search for factors to predict response to treatment and increase overall survival is underway., Objective: This study aimed to analyze the presence of 32 HPV genotypes in tumor samples of 34 patients and the effect of HPV status and RAD51 on overall survival., Method: Tumor samples of 34 patients with locally advanced oropharyngeal or oral cavity cancer treated with accelerated radiotherapy in monotherapy were analyzed using reverse hybridization and immunohistochemistry for the presence of HPV and RAD51. Its effect on overall survival was examined., Results: Only two types of HPV were identified-HPV 16 (dominant) and HPV 66 (two samples). The HPV positivity was associated with a borderline insignificant improvement in 2-year ( p = 0.083), 5-year ( p = 0.159), and overall survival ( p = 0.083). Similarly, the RAD51 overexpression was associated with borderline insignificant improvement in 2-year ( p = 0.083) and 5-year ( p = 0.159) survival., Conclusion: We found no statistically significant differences but detected trends toward improvement in the survival of HPV-positive and RAD51 overexpressing patients unfit for surgical treatment or chemotherapy treated with hyperfractionated radiotherapy. The trends, however, indicate that in a larger group of patients, the effects of these two parameters would likely be statistically significant.

Background: Eagle's syndrome (ES) is a term describing a group of symptoms associated with the elongation of the styloid process (SP) of the temporal bone or with ossification of the stylohyoid ligament. Clinically, it manifests through pain in the orofacial and pharyngeal regions, similar to that experienced by patients with temporomandibular joint disease. The presented paper aims to assess the evaluation of the success of surgical treatment and the complications associated with such treatment., Methods: Our retrospective study includes nine patients with ES treated in our Department Oral and Maxillofacial Surgery in years 2019-2023 (median age of 47 years) - all patients affected with this disease out of 2,716 patients examined at our department due to a temporomandibular joint disease. Eight of these patients underwent a surgical resection of the SP. The success and complications in these patients are evaluated in this study., Results: In seven patients, the problems disappeared or at least diminished, which is consistent with data from the literature. Postoperative complications such as deficit of the marginal branch of the facial nerve (n. VII), limited sticking the tongue out (n. XII), and velopharyngeal insufficiency (n. IX) occurred in three patients., Conclusion: The wide spectrum of clinical manifestations makes ES a condition that should be considered in the differential diagnosis of temporomandibular joint disorders, post-traumatic conditions, or complicated eruption of wisdom teeth or their extraction. ES can be treated conservatively or (mostly) surgically. Surgical treatment can be relatively successful and effective, but it is necessary to respect the anatomical placement of the SP, which can be associated with the development of complications, especially in cases with extremely long SP.

Carcinomas of the oral cavity and oropharynx belong among the ten most common malignancies in the human population. The prognosis of head and neck squamous cell carcinoma (HNSCC) is determined by the degree of invasiveness of the primary tumor and by the extent of metastatic spread into regional and distant lymph nodes. Moreover, the level of the perineural invasion itself associates with tumor localization, invasion's extent, and the presence of nodal metastases. Here, we summarize the current knowledge about different aspects of epigenetic changes, which can be associated with HNSCC while focusing on perineural invasion (PNI). We review epigenetic modifications of the genes involved in the PNI process in HNSCC from the omics perspective and specific epigenetic modifications in OSCC or other neurotropic cancers associated with perineural invasion. Moreover, we summarize DNA methylation status of tumor-suppressor genes, methylation and demethylation enzymes and histone post-translational modifications associated with PNI. The influence of other epigenetic factors on the HNSCC incidence and perineural invasion such as tobacco, alcohol and oral microbiome is overviewed and HPV infection is discussed as an epigenetic factor associated with OSCC and related perineural invasion. Understanding epigenetic regulations of axon growth that lead to tumorous spread or uncovering the molecular control of axon interaction with cancer tissue can help to discover new therapeutic targets for these tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hurník, Chyra, Ševčíková, Štembírek, Trtková, Gaykalova, Buchtová and Hrubá.)