Search Results (526)

The aim of this systematic survey was to evaluate the quality of clinical practice guidelines (CPGs) that provide recommendations for the detection, diagnosis, and treatment of oral cavity cancer (OCC). We conducted a systematic search in MEDLINE, EMBASE, Epistemonikos, CPG websites, and scientific societies to identify documents providing recommendations for the detection, diagnosis, and treatment of OCC. Two reviewers independently assessed the included CPGs using the AGREE II instrument. We calculated standardized scores for the six domains and provided a final recommendation for each CPG. We identified twenty-five CPGs published between 2019 and 2024. The mean scores (higher scores indicate better domain assessment) per domain were as follows: scope and purpose, 80.5 ± 11.6%; stakeholder involvement, 55.6 ± 16.7%; rigor of development, 48.3 ± 20.1%; clarity of presentation, 83.8 ± 8.2%; applicability, 33.6 ± 19.1%; and editorial independence, 57.3 ± 22.4%. The overall mean rate was 4.8 ± 0.8, with a maximum score of seven. Reviewers recommended five guidelines for use in practice, twelve were recommended with modifications, and eight were not recommended. The overall quality of CPGs on OCC was suboptimal. CPG developers should strengthen the use of systematic, transparent methodologies and frameworks for evidence synthesis and recommendation formulation, thereby improving the quality of recommendations and facilitating implementation across diverse clinical contexts. Full article

Introduction: The ecto-endodermal boundary in the human oral cavity remains debated. Rather than a distinct line, this transition forms a complex interface, especially in the developing mouth and pharynx. This ambiguity is clinically relevant, as, for example, HPV-induced tumors often arise where ecto- and endoderm meet. The boundary is generally placed at the posterior third of the tongue and behind the uvula, though its developmental basis remains unclear. This review summarizes the literature on the embryological development of the mouth and pharynx to trace origins and interactions of ectodermal and endodermal derivatives and identify potential tumor initiation regions. Methods: PubMed articles on oral structures were reviewed to approximate the ecto-endodermal border. Results: Teeth originate from ectoderm. The origin of salivary glands and papillae depends on their location. No study reports were found for the tonsils, incisive papilla, tubarial glands, and faucial pillars. Conclusions: A clear educational image of the origin of the structures of the human mouth is made to help identify regions of risk for oral cancer. Full article

The oral cavity represents one of the most demanding operating environments for biomedical coatings, subjecting materials to constant masticatory shear and tribological stress, dynamic temperature fluctuations, salivary enzymatic activity, and continuous fluid turnover that collectively challenge coating adhesion, durability, and longevity. Thermosensitive hydrogels that undergo reversible sol–gel transitions near body temperature offer a uniquely versatile platform for in situ coating formation on complex oral surfaces, enabling minimally invasive application and conformal coverage of irregular anatomical structures—from periodontal pockets and root canal systems to extraction sockets and bone defects. This review examines the application of thermo-sensitive hydrogel coatings across six major oral disease categories: periodontitis, peri-implantitis, bone defects, endodontic diseases, extraction wounds, and oral cancer. We further discuss practical hurdles facing clinical translation, noting that sterilization often degrades these materials, mechanical properties may prove inadequate under masticatory loads, and long-term biosafety data remains limited. This review critically evaluates how these smart coatings can bridge the gap between laboratory innovation and clinical application, offering insights to guide the development of next-generation precision therapies for oral diseases. Full article

Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is an aggressive cancer of the oral cavity, pharynx, larynx and upper airway. HNSCC is subdivided into distinct clinical entities based on the presence or absence of high-risk human papillomavirus (HPV) infection. While HPV-positive HNSCC patients respond better to conventional and targeted therapies than HPV-negative cases, recurrence is more frequent in HPV-negative cases with limited treatment options. Ferroptosis is a form of iron-based programmed cell death caused by excessive lipid peroxide accumulation. Biomarkers of ferroptosis have proven useful for identifying and triggering ferroptosis in models of treatment-resistant cancers. Identifying and understanding ferroptosis biomarker function in HPV-negative HNSCC allows the possibility for more effective treatment strategies. Methods: Literature searches combined with the public online ferroptosis database FerrDB V3 were utilized for the objective identification and classification of established and non-established ferroptosis biomarkers in HPV-negative HNSCC. Additional novel biomarkers were identified based on known roles in HNSCC oncogenesis. Results: A total of 30 ferroptosis biomarkers were identified associated with HPV-negative disease. Biomarkers were grouped according to shared biological functions, with each marker summarized for prognostic and mechanistic roles in HNSCC ferroptosis. Conclusions: The described biomarkers present a means for stratifying tumors for ferroptotic induction, with several offering potential novel methods for overcoming refractory HPV-negative disease. These biomarkers may warrant further investigation into devising future patient-tolerant strategies that selectively activate ferroptosis in HPV-negative HNSCC. Full article

Saliva is a promising diagnostic fluid for studying diseases, including cancer. Saliva composition can reflect both local processes occurring in the oral cavity and systemic changes associated with distant tumors. This review examines changes in salivary electrolyte, amino acid, lipid, and cytokine profiles, tumor markers, and the oral microbiome in cancer. Collectively, these aspects reflect metabolic, inflammatory, immune, secretory, and tumor-associated processes. Metabolites can enter saliva via the salivary glands, systemic circulation, gingival fluid, extracellular vesicles, and oral cells, as well as directly from the site of disease during localized pathological processes. In tumors not localized in the oral cavity, changes in saliva composition are more often associated with systemic inflammation, altered oral microbiome, metabolic reprogramming, oxidative stress, and tumor-associated exosomes. Individual metabolites have limited specificity and cannot be used as independent diagnostic indicators. A comprehensive multimarker analysis of saliva is of greatest value. This approach can facilitate early diagnosis, identify the risk of disease development and progression, monitor therapy, and understand the biological changes associated with the pathological process, including tumors. Full article

Background/Objectives: Occult cervical nodal metastasis drives prognosis in oral cavity squamous cell carcinoma (OCSCC), yet current tools for risk stratification in clinically node-negative (cN0) patients are imperfect. Machine learning (ML) models have been proposed to refine selection for elective neck dissection (END), but their diagnostic performance and generalizability are unclear. Methods: We performed a diagnostic test accuracy systematic review and meta-analysis of ML models predicting occult nodal metastasis in adults with cN0 OCSCC. Eligible studies evaluated an ML-based model, used pathologic nodal status as the reference standard, and reported or allowed reconstruction of sensitivity and specificity. Internal and external validation were distinguished; quantitative synthesis was restricted to non-overlapping external validation cohorts. Diagnostic performance was synthesized with a bivariate random-effects hierarchical summary receiver operating characteristic (HSROC) model, with prespecified sensitivity analyses restricting to lower-risk patient-selection cohorts, models using only preoperative predictors, and non-outlying cohorts. Results: Thirteen retrospective studies (4730 patients) met inclusion; pooled occult nodal metastasis prevalence was 23.6% (crude 20.4%). Eight studies reported only internal validation; five provided six external validation cohorts. Across these external cohorts, pooled sensitivity was 0.79 (95% CI, 0.64–0.89) and specificity 0.84 (95% CI, 0.70–0.93). Negative predictive values were consistently high (0.94–0.98), whereas positive predictive values were modest (0.39–0.85). Sensitivity analyses yielded similar summary estimates with wider confidence intervals. Conclusions: Externally validated ML models for predicting occult nodal metastasis in cN0 OCSCC show promise but remain insufficiently validated to guide END in routine practice. Full article

Background/Objectives: Machine learning (ML) models have increasingly been applied to prognostic prediction in oral cavity squamous cell carcinoma (OCSCC), though their performance and methodological quality remain variably reported. This systematic review evaluated contemporary ML-based prognostic models for clinically relevant OCSCC outcomes, with emphasis on independently validated studies. Methods: A systematic review was conducted according to PRISMA guidelines using PubMed, Scopus, Cochrane Library, and CINAHL databases through 1 December 2025. Studies evaluating ML or artificial intelligence prognostic models in adult OCSCC patients were included. Outcomes included overall survival, recurrence, disease-free survival, recurrence-free survival, disease-specific survival, cancer-specific survival, progression, and nodal metastasis. Data extraction and risk-of-bias assessment using PROBAST + AI were performed independently by reviewers. Results: Forty studies comprising 105,619 patients met inclusion criteria. ML architectures included random forests, support vector machines, gradient boosting methods, neural networks, and deep learning frameworks. Most models incorporated clinical and pathologic variables, while many integrated radiologic, immunologic, or genomic features. For overall survival prediction, independently validated models generally demonstrated AUCs between 0.80 and 0.90. Recurrence prediction models similarly showed favorable discrimination, with most externally validated studies reporting acceptable predictive performance. Additional prognostic endpoints including disease-free survival, progression, and nodal metastasis demonstrated AUCs ranging from 0.70 to 0.90. Common methodological limitations included retrospective design, small sample size, inadequate external validation, and risk of overfitting. Conclusions: ML-based prognostic models in OCSCC demonstrate generally favorable predictive performance across survival and recurrence outcomes. However, substantial heterogeneity in methodology and limited external validation continue to restrict clinical implementation. Future work should prioritize prospective multicenter validation, standardized reporting, and reproducible modeling frameworks. Full article

Ectopic olfactory receptors (ORs) are G protein-coupled chemosensors expressed outside the olfactory epithelium, where they may couple local chemical inputs to cell-specific signaling. The oral cavity is continuously exposed to food-derived compounds, microbial metabolites, volatile organic compounds, and inflammation-associated metabolites, yet the molecular roles of oral ORs remain incompletely defined. This review critically synthesizes current evidence for OR expression and signaling in oral tissues and associated cell populations, with emphasis on ligand–receptor–signaling relationships and disease relevance. Functional OR signaling has been demonstrated in mammalian taste cells, while emerging transcriptomic studies in oral mucosa and transcriptomic/localization studies in the periodontal ligament indicate OR-related programs during tissue-specific or repair-associated states. Candidate metabolic axes, including short-chain fatty acids and lactate linked to OR51E1/OR51E2/Olfr78-related pathways in non-oral models, provide testable mechanistic hypotheses for microbiome–host communication in periodontitis and oral cancer; however, direct causal validation in oral disease models remains limited. We propose an evidence-tiered framework integrating spatial expression mapping, metabolomics-guided deorphanization, receptor perturbation, and longitudinal oral-fluid profiling. Oral ORs should currently be regarded as candidate molecular modulators and components of multimodal biomarker strategies rather than validated standalone diagnostic or therapeutic targets. Full article

Background/Objectives: Radiotherapy (RT) for head and neck cancer (HNC) is associated with oral and functional toxicity, but integrated data combining dental status, nutritional indicators and patient-reported outcomes remain limited. This study evaluated oral, dental, functional, nutritional and quality-of-life outcomes after RT. Methods: This exploratory observational study combined a retrospective record review with a prospective cross-sectional assessment of patient-reported outcomes and included 20 adults treated with RT for HNC in a regional Slovenian clinical setting. Clinical, oncological, dental and nutritional variables were extracted from records, while patient-reported outcomes were assessed once at post-treatment follow-up using the EORTC QLQ-C30, EORTC QLQ-HN43 and a focused oral-health questionnaire. Results: The median time from RT completion to questionnaire assessment was 3.0 months. Dysphagia, xerostomia and taste disturbances after treatment were recorded in 85.0%, 80.0% and 75.0% of patients, respectively. Trismus was present in 40.0%, and weight loss >10% in 55.0%. QLQ-HN43 domains with the highest burden included fear of progression, dry mouth/sticky saliva, problems opening the mouth, social eating, weight loss and teeth problems. Swallowing was strongly associated with social eating (rho = 0.798, p < 0.001), and mouth opening was inversely associated with patient-reported problems opening the mouth (rho = −0.610, p = 0.004). Conclusions: In this small exploratory cohort, substantial early post-treatment oral-functional morbidity was observed. The findings suggest the potential value of integrated survivorship follow-up incorporating dental, nutritional, functional, and patient-reported outcome monitoring. Full article

Oral squamous-cell carcinoma (OSCC) is the most common form of oral cancer, accounting for over 90% of malignancies in the oral cavity. Its pathogenesis is driven by a complex interplay of genetic alterations, transcriptomic dysregulation, epigenetic modifications, environmental exposures, and tumor microenvironment dynamics. Despite advances in therapy, OSCC remains associated with poor survival due to late diagnosis, therapeutic resistance, and tumor heterogeneity. This narrative review explores genetic determinants and molecular mechanisms underlying OSCC, focusing on recurrent mutations, deregulated pathways, epigenetic control, gene expression changes, insights from cell models, and potential biomarkers for diagnosis and therapy. We integrate findings from the recent literature to provide a comprehensive overview of the current state of research and emerging trends in OSCC genetics. Full article

Background/Objectives: Oral cavity squamous cell carcinoma (OSCC) remains a major global health burden, with outcomes strongly dependent on stage at diagnosis. Although the oral cavity is directly accessible to clinical examination, many cases are still detected at advanced stages. This narrative review aimed to summarize current trends in OSCC diagnosis and early monitoring, with emphasis on non-invasive and minimally invasive techniques and biomarkers. Methods: A semi-systematic narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science using predefined combinations of OSCC-, early-detection-, imaging-, cytology-, liquid-biopsy-, salivaomics-, artificial-intelligence-, and biosensor-related terms. English-language systematic reviews, meta-analyses, reviews of reviews, translational studies, and clinically relevant original articles were prioritized, with explicit attention to oral cavity-specific evidence and clearly identified extrapolation from broader head-and-neck or oropharyngeal cancer settings. Results: Conventional oral examination and histopathological assessment of biopsy specimens remain the diagnostic foundation. Adjunctive methods may support lesion triage, biopsy-site selection, risk stratification, and early monitoring, but cannot replace tissue diagnosis. Narrow-band imaging, optical coherence tomography, and molecular brush cytology appear particularly promising for specialist assessment and surveillance. Liquid biopsy and saliva-based biomarker platforms offer translational potential, particularly for repeatable monitoring, but clinical implementation is limited by methodological heterogeneity, pre-analytical variability, inconsistent thresholds, and insufficient external validation. Artificial intelligence and biosensor platforms remain promising but largely developmental. Conclusions: Progress in early OSCC diagnosis and monitoring will most likely depend on integrated diagnostic models combining clinical examination, adjunctive imaging, minimally invasive sampling, molecular biomarkers, and computational decision-support tools, validated in prospective multicenter studies. Full article

Background: Cancer treatment-induced ulcerative mucositis (UM) is a debilitating toxicity in patients with cancers of the lip, oral cavity, and pharynx (CLOP). This study evaluated the association of chemotherapy-induced (CT-UM) and radiotherapy-induced ulcerative mucositis (RT-UM) with burden of illness (BOI), focusing on hospital length of stay (LOS) and total charges, and examined disparities in outcomes. Methods: This retrospective cohort study analyzed 2019 National Inpatient Sample (NIS) data. Adult patients (≥18 years) hospitalized with CLOP (ICD-10-CM C00–C14) undergoing inpatient surgery, chemotherapy, or radiotherapy were included. CT-UM (K12.31) and RT-UM (K12.33) were identified as secondary diagnoses. Survey-weighted generalized linear models (negative binomial for LOS; gamma for charges) adjusted for demographics, comorbidities (Elixhauser score), insurance, income, and Diagnosis-Related Groups (DRG; surgical vs. medical) were used. Results: Among 59,710 weighted CLOP hospitalizations, 820 had CT-UM and 1010 had RT-UM. Patients with UM were younger and had varying comorbidity burdens. Unadjusted analyses showed prolonged geometric mean LOS for CT-UM (5.66 vs. 3.81 days, p < 0.001) and RT-UM (4.95 vs. 3.81 days, p = 0.001), with lower total charges ($48,645 and $42,938 vs. $56,267). Multivariable analyses confirmed RT-UM was associated with increased LOS (adjusted coefficient 1.33, 95% CI 1.14–1.55) but lower charges (0.67, 95% CI 0.56–0.81). In patients >50 years, CT-UM showed stronger effects (LOS 1.80, 95% CI 1.49–2.15; charges 0.79, 95% CI 0.65–0.98). Significant disparities were observed: females, Black and Hispanic patients, and Medicaid beneficiaries experienced greater BOI (prolonged LOS and/or higher charges in subgroups). Associations persisted in DRG- and procedure-stratified sensitivity analyses, suggesting treatment interruptions as a key driver. Conclusions: Ulcerative mucositis in hospitalized CLOP patients is associated with prolonged LOS but lower charges, likely due to treatment modifications, and disproportionately affects vulnerable populations. These findings highlight the need for proactive oral care protocols, multidisciplinary integration, and equity-focused interventions to reduce the burden of this toxicity and improve cancer treatment outcomes. Full article

Pancreatic cancer (PC) remains one of the malignancies with the most unfavorable prognosis and limited treatment options. The lack of biomarkers for early diagnosis and the asymptomatic nature of the disease contribute to delays in diagnosis and high mortality rates. In recent years, the role of the human microbiota in cancer biology has become increasingly significant, and the oral microbiota in particular has been found to be involved in the pathogenesis and prognosis of several neoplasms. This review summarizes the current evidence relating the salivary microbiota to PC in three key areas: screening and diagnostic potential, pathophysiology and tumor progression, as well as presenting prognostic implications and potential influence on therapy. With regard to early diagnosis, it has been reported that patients with PC have reduced levels of Neisseria elongata (N. elongata) and Streptococcus mitis (S. mitis) and elevated levels of Granulicatella adiacens. Several studies have shown that bacteria present in the saliva can migrate from the oral cavity to pancreatic tissue via hematogenous or enteric routes, where they may actively contribute to tumor development and progression. In particular, it has been shown that Porphyromonas gingivalis (P. gingivalis) and Veillonella atypica (V. atypica) translocate from the mouth to pancreatic tumors, promoting carcinogenesis by inducing a pro-inflammatory tumor microenvironment. Furthermore, some studies have identified certain species associated with prognosis and response to PC treatment. Despite the encouraging results, differences in study methodology, the lack of standardized methods and the scarcity of longitudinal data currently hinder clinical application. Large-scale, multi-omics prospective studies are needed to clarify causality and validate their clinical utility. Overall, the salivary microbiota represents a promising and non-invasive tool for improving early diagnosis, understanding prognosis and enhancing the management of PC. Full article

Background and objectives: Sentinel lymph node biopsy (SLNB) has become the standard approach for cervical staging in patients with early-stage oral cavity squamous cell carcinoma (OCSCC). Although it demonstrates diagnostic accuracy exceeding 90% in referral centres, the occurrence of false-negative (FN) results undermines oncological safety and adversely impacts patient prognosis. This scoping review aims to synthesise and evaluate the scientific evidence regarding the risk factors and technical errors that underpin FN incidence. Methods: A systematic search was conducted across MEDLINE (PubMed), Scopus and Web of Science for studies published between 2000 and 2025, adhering to PRISMA-ScR guidelines. Primary clinical and observational studies specifically addressing the variables and aetiology of diagnostic failure in SLNB for early-stage OCSCC (cT1-T2 N0) were included. Results: Twenty-seven studies were included in the final qualitative synthesis. Four critical domains characterising FN risk were elucidated, facilitating risk-stratified selection and surveillance strategies: (1) Clinical and tumour factors: Depth of invasion >4–5 mm, T3–T4 tumour size, and prior cervical anatomical disruption. (2) Surgical factors: Insufficient sentinel lymph node (SLN) harvest (≤2 SLNs), lack of exhaustive lymphatic basin exploration, the initial learning curve, and the exclusive use of non-isotopic tracers. (3) Anatomical factors: Floor of the mouth tumours and the radioactive shine-through effect. (4) Histopathological protocol: Suboptimal ultrastaging, insufficient frozen section biopsy, and limitations in rapid molecular techniques. Overall, studies using standardised protocols report a false-negative rate between 5% and 15%. Conclusions: FN events in SLNB are multifactorial and predictable phenomena, arising from cumulative vulnerabilities along the diagnostic continuum. The technique achieves an optimal diagnostic yield in cT1–T2 N0 cases without prior cervical treatment when applied under optimal conditions. However, methodological heterogeneity in the literature limits the interpretation of the results and partially constrains their clinical application. Full article

Background/Objectives: Behçet’s disease is a chronic relapsing multisystem inflammatory disorder characterized by recurrent mucocutaneous ulceration, vasculitis, and exaggerated inflammatory responses to minor trauma. These features may adversely affect wound healing after major head and neck oncologic reconstruction. This case report describes repeated wound breakdown after oral cavity reconstruction in a patient with Behçet’s disease and advanced floor-of-mouth squamous cell carcinoma. Methods: A 51-year-old woman with Behçet’s disease and T4N2bM0 squamous cell carcinoma involving the floor of the mouth and tongue underwent tumor resection followed by reconstruction of the oral cavity defect using a right anterolateral thigh perforator free flap. Subsequent surgical procedures included debridement of necrotic tissue, negative-pressure wound therapy, split-thickness skin grafting of the thigh donor site, and salvage tumor resection with pectoralis major myocutaneous flap reconstruction after tumor recurrence. Results: After the initial anterolateral thigh free flap reconstruction, flap perfusion was satisfactory in the immediate postoperative period; however, delayed marginal necrosis developed from the distal tongue-side flap margin, whereas the floor-of-mouth portion remained relatively stable. The right thigh donor site also developed progressive suture-line necrosis and wound dehiscence, requiring operative debridement, negative-pressure wound therapy, and split-thickness skin grafting. Although skin grafting achieved eventual donor-site coverage, partial graft necrosis and delayed secondary healing occurred. Persistent fistula and wound instability delayed postoperative radiotherapy, and recurrent floor-of-mouth squamous cell carcinoma subsequently developed approximately 6 months after the initial surgery. After salvage resection and pectoralis major myocutaneous flap reconstruction, the flap appeared viable at inset, but marginal ecchymosis, partial necrosis, and wound dehiscence again developed, requiring additional debridement, quilting sutures, and negative-pressure wound therapy. The wound gradually stabilized with staged wound management. Conclusions: This case illustrates a multifactorial pattern of repeated marginal wound breakdown after technically successful flap reconstruction in a patient with Behçet’s disease. Behçet-related pathergy-like inflammation, vasculitis, and microcirculatory dysfunction may represent possible contributing mechanisms, but they were not directly proven in this patient. In oral cavity reconstruction, such wound instability may delay adjuvant therapy and adversely affect oncologic outcomes. Careful perioperative planning, close multidisciplinary coordination, meticulous tension-free closure, early recognition of wound compromise, and readiness for staged wound management are essential in patients with Behçet’s disease undergoing major head and neck oncologic reconstruction. Full article