Search Results (1,460)

Background: MiRNAs have emerged as minimally invasive biomarkers with considerable potential for the early detection of oral squamous cell carcinoma (OSCC). Although numerous studies have evaluated circulating miRNAs across different biofluids, the comparative diagnostic performance of saliva-, serum-, and plasma-derived miRNAs has not been systematically clarified. Methods: A meta-analysis was performed by screening PubMed, MEDLINE, Scopus, CINAHL, and related databases. Nineteen eligible studies evaluating miRNA-based assays in saliva, serum, or plasma were included. A random-effects bivariate model was used to calculate pooled sensitivity, specificity, and area under the HSROC curve. Meta-regression using log diagnostic odds ratio (lnDOR) examined whether biofluid type significantly influenced diagnostic performance. Results: Salivary miRNAs showed a pooled sensitivity of 0.76 (95% CI: 0.68–0.82; I² = 84.69%), specificity of 0.79 (95% CI: 0.70–0.85; I² = 70.41%), and an AUC of 0.84 (95% CI: 0.80–0.87). Plasma miRNAs produced comparable results with a pooled sensitivity of 0.77 (95% CI: 0.61–0.88; I² = 90.45%), specificity of 0.79 (95% CI: 0.63–0.89; I² = 80.20%), and an AUC of 0.85 (95% CI: 0.81–0.89). Serum-derived miRNAs demonstrated the highest accuracy with a pooled sensitivity of 0.82 (95% CI: 0.70–0.90; I² = 76.92%), specificity of 0.88 (95% CI: 0.75–0.95; I² = 74.87%), and an AUC of 0.91 (95% CI: 0.89–0.94). Despite serum’s numerically superior performance, meta-regression revealed no significant matrix effect (Wald χ² = 0.20, p = 0.903). Conclusions: Although serum-derived miRNAs performed best overall, biofluid type was not a statistically significant determinant of diagnostic performance. Full article

Background: Three-dimensional virtual surgical planning (Three-dimensional VSP) has become standard practice in the treatment of mandibular oral squamous cell carcinoma (OSCC) in the last decade. Dutch guidelines recommend a care pathway interval (CPI) of a maximum of 30 days, and a free bone margin of at least 5 mm. Fused MRI and CT data are used for accurate tumor delineation. Based on this data, a virtual surgical plan is created and transferred to the operating room using resection guides and patient-specific implants (PSIs). Long-term evaluation is needed to further optimize its clinical use. Objectives: This study evaluates adherence to bone margin and CPI guidelines in mandibular OSCC. Additionally, it assesses the accuracy of tumor resection and reconstruction using 3D-VSP and compares the complications of 3D-planned mandibular reconstruction using different kinds of osteosynthesis plates. Methods: All patients who underwent a segmental mandibulectomy between 2014 and 2024 at the University Medical Center Groningen were included. CPI, clinical outcomes, and complications were analyzed. The preoperative virtual plan was compared with the postoperative outcome to assess accuracy. Results: The median CPI was 34 days, and 93.7% of bone margins were tumor-free. Mean absolute resection deviation was 1.63 mm (±1.42). PSI reconstructions were significantly more accurate in intergonial distance and coronal angle compared to conventional plates. Plate-related complications were more common in non-bony reconstructions; PSI reconstructions showed significantly more plate exposure. Conclusions: 3D-VSP leads to high accuracy in resection and reconstruction and favorable bone margins. Shortening the CPI and reducing biological complications are essential to further improve oncological outcomes. Full article

This retrospective study provides an extensive evaluation of feline squamous cell carcinoma (SCC), comparing oral and cutaneous SCC, as well as different oral/cutaneous sites, with respect to sex, age, breed, and coat length. It was based on 4300 SCCs submitted to LABOKLIN GmbH & Co. KG from 2017 to 2023. No sex predisposition was identified. Affected cats were predominantly older (median age 13 years). SCC risk increased with age, although cats of very young age were also affected. Breed predispositions were not found. However, compared to non-pedigree cats, Persians, Norwegian Forest Cats, British Shorthairs (BSH), Chartreux, and Siamese cats showed a reduced risk, as did longhaired cats. The predominant sites were the oral cavity (41.0%, 1762/4300) and skin (35.8%, 1540/4300). Maine Coons, BSHs, Persians, and Norwegian Forest Cats, as well as longhaired cats, developed oral SCC more frequently. Intraoral, gingival (36.2%, 637/1762) and lingual (19.0%, 334/1762) SCC predominated. Common cutaneous sites included the pinnae (35.0%, 539/1540), unspecified head/neck regions (8.8%, 135/1540), and the nose (8.7%, 134/1540). Maine Coons and BSHs showed less auricular SCC; Sphynx had more on the trunk. These findings emphasise SCC as a crucial differential diagnosis for oral and cutaneous lesions, even in young cats. Full article

Oral squamous cell carcinoma (OSCC) is an aggressive disease with a glycoproteomically unmapped progression and a low five-year survival rate. Thus, the aim of this pilot study was to explore the N-glycosylation pattern differences in malignant, adjacent mucosal and healthy tissues in the context of OSCC. Oral mucosal soft tissue samples was obtained by incisional biopsy from five patients with OSCC, both from the malignant and the opposite healthy gingival sides, and from seven age-sex-matched healthy controls. The collected tissues were homogenized, followed by N-glycan profiling of the endoglycosidase-released and fluorophore-labeled carbohydrates using capillary electrophoresis with ultra-sensitive laser-induced fluorescent detection (CE-LIF). Six out of the twenty-two identified N-glycan structures, including glycogens, showed significant (p < 0.05) differences between the malignant tissue samples of the OSCC patients and the healthy controls. Comparing the healthy and the positive control oral mucosal samples, differences in four N-glycan structures were revealed, while only one alteration was observed between the N-glycan profiles of the malignant tumor and positive control samples. However, the results are presented descriptively, reflecting the limited sample size of the pilot study, it shows the potential of high-resolution CE-LIF-based glyocoanalytical protocol to be highly efficient and sensitive for glycobiomarker-based molecular diagnostics of oral malignant lesions. Full article

Oral squamous cell carcinoma (OSCC) is one of the most prevalent types of cancer in the oral cavity and head and neck region. Due to its location and psychological and social implications, early detection and treatment are very important. A liquid biopsy can be used to diagnose cancer by analyzing samples of bodily fluids, such as saliva, blood, or urine, for specific molecules released by tumor cells. The objective of this study was to evaluate the use of liquid biopsy in the diagnosis of oral squamous cell carcinoma. A systematic review was carried out, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO: CRD420251238037). Articles taken into consideration for the review were published before 30 September 2025. The search for manuscripts for the review was conducted using PubMed, Scopus, Google Scholar, and Cochrane databases. Forty-three articles were deemed eligible for inclusion in the systematic review. Key data extracted from the studies included authorship, publication date, study location, methodology, number of participants, and reported complications. Most of the analyzed biomarkers showed promising potential for future use in liquid biopsy for OSCC diagnosis. Tumor DNA and miRNA demonstrated the highest diagnostic accuracy. The standard approach to diagnosis and planning treatment relies on tumor biopsy and diagnostic imaging. Liquid biopsy may complement this process by enabling early detection in high-risk populations and monitoring response to therapy. As such, it serves as a prognostic factor or therapeutic target, successfully identifying disease recurrence. Full article

Acrolein, a highly reactive environmental toxicant widely present in urban air and tobacco smoke, has been implicated in the development of multiple malignancies. In oral tissues, chronic acrolein exposure induces oxidative stress, inflammation, and genetic mutations, all of which are closely linked to the development of oral squamous cell carcinoma (OSCC). Although accumulating evidence indicates a strong association between acrolein exposure and OSCC, its prognostic significance remains poorly understood. In this study, we analyzed transcriptome data to identify differentially expressed genes (DEGs) between tumor and adjacent normal tissues, and screened acrolein-related candidates by intersecting DEGs with previously identified acrolein-associated gene sets. Functional alterations of these genes were assessed using Gene Set Variation Analysis (GSVA), and a protein–protein interaction (PPI) network was constructed to identify key regulatory genes. A prognostic model was developed using Support Vector Machine–Recursive Feature Elimination (SVM-RFE) combined with LASSO-Cox regression and validated in an independent external cohort. Among the acrolein-related DEGs, four key genes (PLK1, AURKA, CTLA4, and PPARG) were ultimately selected for model construction. Kaplan–Meier analysis showed significantly worse overall survival in the high-risk group (p < 0.0001). Receiver operating characteristic (ROC) curve analysis further confirmed the strong predictive performance of the model, with area under the curve (AUC) values of 0.72 at 1 year, 0.72 at 3 years, and 0.75 at 5 years. Furthermore, the high risk score was significantly correlated with a ‘cold’ immune microenviroment, suggesting that acrolein-related genes may modulate the tumor immune microenvironment. Collectively, these findings highlight the role of acrolein in OSCC progression, suggesting the importance of reducing acrolein exposure for cancer prevention and public health, and call for increased attention to the relationship between environmental toxicants and disease initiation, providing a scientific basis for public health interventions and cancer prevention strategies. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to treatment-related toxicity and impaired oral tissue regeneration. This study aimed to develop and characterize a novel biocomposite based on bioactive compounds from Ganoderma lucidum incorporated into marine collagen derived from Rhizostoma pulmo and to evaluate its physicochemical properties, antioxidant and antimicrobial activities, and in vitro antitumor potential in the oral cavity. Methods: Hydroalcoholic extracts of G. lucidum and pepsin-soluble collagen peptides from R. pulmo jellyfish were prepared and combined to obtain two hydrogel biocomposites with different component ratios. Chemical and structural characterization was performed using HPLC-DAD, SDS-PAGE, FT-IR, circular dichroism, and spectrophotometric assays. Antioxidant activity was assessed by DPPH radical scavenging and reducing power assays, while antimicrobial activity was evaluated against oral pathogens using diffusion and MIC methods. In vitro biological activity was investigated using MTT viability and scratch migration assays on human OSCC cell lines (SCC-9 and HSC-3). Results: The biocomposites preserved the structural integrity of type I collagen and incorporated polysaccharides and polyphenols from G. lucidum. The combined formulations showed enhanced antioxidant and antimicrobial activities compared with collagen alone. In vitro assays demonstrated dose- and time-dependent reductions in OSCC cell viability and delayed cell migration, with effects comparable to those of G. lucidum extract. Conclusions: The G. lucidum–R. pulmo biocomposite exhibits favorable physicochemical properties and demonstrates antioxidant, antimicrobial, and in vitro antitumor activity. These findings support its potential as a multifunctional biomaterial for further investigation as an adjunct approach in oral cancer-related applications. Full article

Oral cancer (OC) remains a major global health concern with survival often limited by late diagnosis. Early and accurate detection is essential to improve patient outcomes and guide treatment decisions. In this study we propose a computer aided diagnostic (CAD) framework for classifying oral squamous cell carcinoma from histopathology images. The model combines Swin transformer for hierarchical feature extraction with vision transformer (ViT) to capture long range dependencies across image regions. SHapley Additive exPlanations (SHAP) based feature selection enhances interpretability by highlighting the most informative features while preprocessing steps such as stain normalization and contrast enhancement improve model generalization and reduce sample variability. Evaluated on a publicly available dataset the framework achieved 99.25% accuracy (ACC) 99.21% sensitivity and a matthews correlation coefficient (MCC) of 98.21% outperforming existing methods. Ablation studies highlighted the importance of positional encoding and statistical analyses confirmed the robustness and reliability of results. To support real-time inference and scalable deployment the proposed model has been integrated into a FastAPI-based web application. This framework offers a powerful interpretable and practical tool for early OC detection and has potential for integration into routine clinical workflows. Full article

Oral squamous cell carcinoma (OSCC) remains a highly prevalent and aggressive malignancy with limited improvements in survival rates. One of the major obstacles to successful treatment is the development of chemoresistance, which contributes to recurrence, metastasis, and treatment failure. This narrative review aims to integrate current evidence on the molecular and cellular mechanisms that drive chemoresistance in OSCC and to delineate how these processes converge under therapeutic pressure. A structured search was performed to identify relevant studies addressing chemoresistance in OSCC, focusing on preclinical and translational evidence. Multiple interconnected mechanisms have been implicated in driving resistance in OSCC, including epigenetic alterations, deregulated signaling pathways, cancer stem cell plasticity, epithelial–mesenchymal transition (EMT), interactions with the tumor microenvironment (TME), drug efflux mediated by ATP-binding cassette (ABC) transporters, and enhanced DNA damage response. In combination, these mechanisms support tumor persistence and limit effective antitumor immunity. Emerging strategies such as epigenetic modulators, signaling pathway inhibitors, immunomodulation, and nanomedicine-based delivery systems have shown promising results in preclinical models. By highlighting convergent resistance networks, this integrative perspective supports the rational design of combination therapies and biomarker-guided strategies aimed at overcoming chemoresistance in OSCC. Full article

Background/Objectives: Formation of tight contacts between oral soft tissue and dental implants is a significant challenge in contemporary implantology. An essential role in this process is played by oral epithelial cells. In the present study, we investigated how titanium and zirconia surfaces with different roughness influence various parameters of oral epithelial cells in vitro. Methods: We used the human oral squamous carcinoma Ca9-22 cell line and cultured them on the following surfaces: machined smooth titanium (TiM) and zirconia (ZrM) surfaces, as well as sandblasted and acid-etched titanium moderately rough (SLA) and zirconia (ZLA) surfaces. Cell proliferation/viability was measured by CCK-8 assay, and cell morphology was analyzed by fluorescent microscopy. The gene expression of interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, E-cadherin, integrin (ITG)-α6, and ITG-β4 was measured by qPCR, and the content of IL-8 in conditioned media by ELISA. Results: At the initial culture phase, cell proliferation was promoted by rougher surfaces. Differences in cell attachment were observed between machined and moderately rough surfaces. Machined surfaces were associated with slightly higher IL-8 levels (p < 0.05). Furthermore, both ZLA and SLA surfaces promoted the expression of (ITG)-α, ITG-β4, and ICAM-1 in Ca9-22 cells (p < 0.05). Surface material had no impact on the investigated parameters. Conclusions: Under the limitations of this in vitro study, some properties of oral epithelial cells, particularly the immunological and barrier function, are moderately modified by roughness but not by material. Hence, the roughness of the implant surface might play a role in the quality of the peri-implant epithelium. Full article

Autophagy is a well-preserved biological mechanism that is essential for sustaining homeostasis by degradation and recycling damaged organelles, misfolded proteins, and other cytoplasmic detritus. Cannabinoid signaling has emerged as a prospective regulator of diverse cellular functions, including immunological modulation, oxidative stress response, apoptosis, and autophagy. Dysregulation of autophagy contributes to pathogenesis and treatment resistance of several oral diseases, including oral squamous cell carcinoma (OSCC), periodontitis, and gingival inflammation. This review delineates the molecular crosstalk between cannabinoid receptor type I (CB1) and type II (CB2) activation and autophagic pathways across oral tissues. Cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), modulate key regulators like mTOR, AMPK, and Beclin-1, thereby influencing autophagic flux, inflammation, and apoptosis. Experimental studies indicate that cannabinoids inhibit the PI3K/AKT/mTOR pathway, promote reactive oxygen species (ROS)-induced autophagy, and modulate cytokine secretion, mechanisms that underline their dual anti-inflammatory and anti-cancer capabilities. In addition, cannabinoid-induced autophagy has been shown to enhance stem cell survival and differentiation, offering promise for dental pulp regeneration. Despite these promising prospects, several challenges remain, including receptor selectivity, dose-dependent variability, limited oral bioavailability, and ongoing regulatory constraints. A deeper understanding of the context-dependent regulation of autophagy by cannabinoid signaling could pave the way for innovative therapeutic interventions in dentistry. Tailored cannabinoid-based formulations, engineered for receptor specificity, tissue selectivity, and optimized delivery, hold significant potential to revolutionize oral healthcare by modulating autophagy-related molecular pathways involved in disease resolution and tissue regeneration. Full article

Background/Objectives: Stemness has been proposed as a unifying driver of invasion, treatment resistance, and relapse in oral squamous cell carcinoma (OSCC). We synthesized two complementary evidence streams to determine whether higher stemness predicts poorer survival in OSCC: (i) computational stemness signatures derived from transcriptomic/epigenetic data and (ii) tissue cancer stem cell (CSC) immunophenotypes by immunohistochemistry (IHC). Methods: Following PRISMA 2020, we searched PubMed/MEDLINE, Embase, Scopus, and SciELO. Adults with histologically confirmed OSCC were eligible. Primary outcome was overall survival (OS); disease-specific survival (DSS) and recurrence-free survival (RFS) were secondary. Two parallel meta-analyses pooled effects within domains; random-effects restricted maximum likelihood (REML) models were applied. Results: Of 785 records, 11 studies met criteria. For computational signatures (k = 6), higher stemness was associated with poorer OS (pooled HR 2.24, 95% CI 1.61–3.12; I² ≈ 49%). Sensitivity excluding the single unadjusted Kaplan–Meier (KM)-derived estimate yielded a similar effect (HR 2.13, 95% CI 1.56–2.89). For CSC-IHC (main analysis, k = 2), CSC-positive profiles predicted worse OS (pooled HR 2.01, 95% CI 1.42–2.84; I² ≈ 0%); results were robust to excluding an internally inconsistent study (single-study HR 2.078). An exploratory sensitivity analysis, including a 1-year HR (different time horizon), increased heterogeneity and was not considered definitive. A functional meta-synthesis converged on epithelial–mesenchymal transition/extracellular matrix remodeling, hypoxia/glycolysis, redox/ferroptosis resistance, and ribosome/rRNA biogenesis, supporting biological plausibility across modalities. Conclusions: Across computational and IHC evidence, stemness consistently portends inferior OS in OSCC, offering a biologically anchored framework for risk stratification and testable therapeutic hypotheses. Full article

Background/Objectives: Oral potentially malignant disorders (OPMDs), including oral leukoplakia (OLK), oral lichen planus (OLP), and actinic cheilitis (AC), have varying risks of progression to oral squamous cell carcinoma (OSCC). Biomarkers such as aldehyde dehydrogenase 1 (ALDH1) and mammary serine protease inhibitor (Maspin) have shown potential for diagnostic and prognostic use in oral cancer. The present study aimed to evaluate the immunoexpression of aldehyde dehydrogenase 1, a cancer stem cell marker associated with aggressiveness, and the mammary serine protease inhibitor, a potential tumor suppressor, in OPMD and OSCC tissues. Methods: A retrospective analysis was performed on 145 biopsy specimens collected from January 2015 to January 2023, including normal epithelium, OPMDs (OLK, OLP, AC), and OSCC. ALDH1 and Maspin expression levels were evaluated using immunohistochemistry, considering both the percentage of positive cells and staining intensity. Statistical analyses were carried out using the Statistical Package for the Social Sciences (SPSS, version 29.0; IBM Corp., Chicago, IL, USA). Results: Normal oral epithelium showed no expression of ALDH1, whereas 40.6% of OPMDs and 44.4% of OSCC samples exhibited high cytoplasmic ALDH1 expression. Nuclear ALDH1 expression was elevated in 29.7% of OPMDs and 38.9% of OSCCs (p < 0.001). Nuclear Maspin expression was high in 95.2% of normal tissues, in 67.2% of OPMDs and in 55.6% of OSCCs (p < 0.001). Maspin showed strong nuclear and cytoplasmic expression in normal tissue, but its expression decreased in OPMDs and OSCCs, with statistically significant reductions in both compartments (p < 0.001). Conclusions: The results indicate that ALDH1 upregulation and Maspin downregulation are hallmark events in oral carcinogenesis. Their combined evaluation provides a powerful tool for assessing dysplastic severity and malignant transformation risk in OPMDs. Future studies on larger cohorts are needed to confirm the prognostic utility of this dual-marker model. Full article

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing on thirteen cancers with the strongest and most clinically relevant microbiome associations, colorectal cancer, gastric cancer, hepatocellular carcinoma, gallbladder cancer, esophageal cancer, pancreatic cancer, oral squamous cell carcinoma, cervical cancer, prostate cancer, breast cancer, lung cancer, brain cancer, and melanoma. These cancers were selected based on robust mechanistic data linking microbial alterations to tumor initiation, progression, and therapy modulation, as well as their global health burden and translational potential. In addition, we have provided mechanistic insights or clinical correlations between the microbiome and cancer outcomes. Across cancers, common microbial mechanisms included pro-inflammatory signaling (e.g., NF-κB and STAT3 pathways), DNA damage from bacterial toxins (e.g., colibactin, nitrosating species), and metabolite-driven tumor promotion (e.g., secondary bile acids, trimethylamine N-oxide). Conversely, beneficial commensals such as Faecalibacterium prausnitzii and Akkermansia muciniphila supported antitumor immunity and improved responses to immune checkpoint inhibitors. In conclusion, the gut microbiome functions as both a driver of malignancy and a modifiable determinant of therapeutic success. Integrating microbiome profiling and modulation strategies such as dietary interventions, probiotics, and fecal microbiota transplantation into oncology practice may pave the way for personalized and more effective cancer care. Full article

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with a poor prognosis. Sestrin2 (Sesn2), a stress-inducible protein, has been implicated in various cancers, but its precise role and mechanism in OSCC remain unclear. This study investigated the molecular mechanisms of Sesn2 in OSCC. Sesn2 expression was analyzed using data from TCGA and immunohistochemical results from the HPA. Functional assays, including CCK-8, flow cytometry for cell cycle, wound healing, and Transwell assays, were performed following Sesn2 knockdown with siRNA in OSCC cell lines (CAL-27 and SAS). Underlying mechanisms were investigated by Western blotting and ELISA for MMP-2 and MMP-9 levels. Sesn2 was significantly upregulated in OSCC tissues compared to normal controls. Its knockdown markedly suppressed cell proliferation, induced G1 phase cell cycle arrest, and impaired migratory and invasive capabilities. This reduction in invasion was further confirmed by decreased levels of MMP-2 and MMP-9 upon Sesn2 knockdown. Furthermore, Sesn2 silencing induced apoptosis via Caspase-3 activation with divergent BAX/BCL-2 modulation; SAS cells exhibited elevated BAX and reduced BCL-2, whereas these proteins remained unchanged in CAL-27 cells. Mechanistically, we found that Sesn2 depletion downregulated the PI3K/AKT/mTOR pathway and reduced the phosphorylation of AKT and p38 MAPK. Our findings demonstrate that Sesn2 functions as an oncogene in OSCC, promoting tumor progression by modulating the PI3K/AKT/mTOR and MAPK signaling pathways, suggesting its potential as a therapeutic target for OSCC. Full article