Search Results (925)

Epstein–Barr virus (EBV) is an oncogenic virus implicated in several epithelial malignancies; however, its role in the tumor microenvironment of oral squamous cell carcinoma (OSCC) remains unclear. This study investigated the association between EBV infection and clinicopathological and microenvironmental features of OSCC. A cross-sectional analysis was conducted on 62 archived OSCC biopsy specimens. EBV was detected using polymerase chain reaction (PCR), and clinical data were obtained from medical records. Tumor–stroma ratio (TSR), perineural invasion (PNI), lymphovascular invasion (LVI), and histological differentiation were assessed microscopically, while tumor-infiltrating lymphocytes (TILs) were quantified using ImageJ software version 1.54j (National Institutes of Health, Bethesda, MD, USA). EBV DNA was identified in 43.5% of cases. EBV positivity was significantly associated with older age (p = 0.046), especially among patients aged 60 years or older. All EBV-positive tumors exhibited a high tumor–stroma ratio, which was significantly associated with EBV status (p = 0.031). No significant associations were observed between EBV status and sex, tumor site, clinical stage, TILs, PNI, LVI, or histological differentiation. These findings indicate that EBV-positive OSCC is characterized by distinct microenvironmental features, particularly an elevated tumor–stroma ratio, and suggest a potential role for EBV status in microenvironmental profiling and prognostic stratification. Full article

Oral squamous cell carcinoma (OSCC) accounts for the majority of feline oral neoplasms and carries a poor prognosis; however, the oral microbiome in affected cats remains poorly characterized. This study aimed to preliminarily describe the oral bacterial communities of cats with OSCC and compare them with those of clinically healthy cats using DNA amplicon sequencing. Oral swabs were collected from cats with OSCC, including tumor surfaces, tumor cut surfaces, and clinically normal mucosa distant from the tumor (n = 20 total samples), and from the gingival margin of healthy cats (n = 12). DNA was extracted and full-length 16S rRNA gene sequencing was performed to assess microbial composition and diversity. Cats with OSCC exhibited significant alterations in oral microbiota compared with healthy controls, including reduced alpha diversity, distinct beta-diversity clustering, and consistent taxonomic shifts. Healthy cats displayed a relatively conserved core microbiome dominated by Porphyromonas spp., Bacteroides, Pasteurellaceae, Helcococcus, and Moraxella. In contrast, OSCC-associated samples showed increased relative abundances of anaerobic and disease-associated taxa, including Filifactor villosus, Bacteroides pyogenes, Odoribacter denticanis, Porphyromonas circumdentaria, and members of the Pasteurellaceae. These findings provide the first description of the oral microbiota associated with feline OSCC and demonstrate exploratory microbial differences between health and disease. Full article

Background: Non-smoking, non-drinking (NSND) oral squamous cell carcinoma (OSCC) is increasingly recognized, yet its clinicopathologic and immune-related correlates remain incompletely defined. Methods: We retrospectively studied 243 surgically treated patients with previously untreated primary OSCC (2011–2020). Patients were classified as NSND or smoking and/or drinking (SD). Immune-modulating conditions and preoperative systemic immune–inflammatory indices (NLR, LMR, SIRI, AISI) were assessed, and overall (OS) and disease-specific survival (DSS) were analyzed. Results: Eighty-five patients (35.0%) were NSND. NSND patients were more often female (58.8% vs. 12.7%) and slightly older (median 54 vs. 50 years). Subsite distribution differed (p < 0.001): tongue (52.9%), buccal mucosa (15.3%), and floor of mouth (3.5%) in NSND versus a predominance of floor of mouth tumors in SD (34.8%). NSND tumors showed smaller diameter, lower depth of invasion, less perineural invasion (40.5% vs. 55.1%), and more frequent inflammatory infiltrate (73.8% vs. 60.1%). Immune-modulating conditions were enriched in NSND (67.1% vs. 17.7%; p < 0.001; adjusted OR 6.25, 95% CI 3.23–12.11), particularly among NSND patients >50 years (79.2%). NSND patients showed lower NLR (p = 0.01), lower SIRI and AISI (p < 0.001), and higher LMR (p < 0.001). Median OS was 81.2 months; NSND showed a trend toward improved OS (p = 0.083) and improved OS after age/sex adjustment (HR 0.64, 95% CI 0.42–0.98), but not after full clinicopathologic adjustment; DSS did not differ (p = 0.59). Conclusions: NSND OSCC exhibits a distinct clinicopathologic presentation and is strongly associated with immune-modulating comorbidity and lower tumor-associated systemic inflammatory indices, consistent with an immune-modulated clinical phenotype. Full article

Background/Objectives: Oral mucosal wounds are frequently encountered in daily dental practice and are often difficult to manage because of continuous exposure to saliva, mastication, and mechanical irritation. This technical note describes the clinical practicality of an oral liquid bandage (ORAPLA) as a film-forming protective barrier for traumatic and surgical oral mucosal wounds. Methods: ORAPLA was applied in four clinical scenarios: a traumatic lip bite injury, a postoperative mucosal defect following leukoplakia excision, a biopsy wound for suspected oral squamous cell carcinoma (OSCC), and aphthous stomatitis. Clinical observations included patient-reported symptom relief, film retention, and the clinical appearance of epithelialization at follow-up (1–2 weeks). Results: In all cases, ORAPLA formed a thin protective film immediately after application and was typically observed to remain on the wound surface for approximately 5–6 h under routine daily activities. Patients reported prompt subjective pain relief, and no adverse events were observed. Epithelialization proceeded without clinically evident secondary infection during the follow-up period. Conclusions: In this small descriptive case series, ORAPLA was feasible to apply, well tolerated, and provided temporary mechanical protection with immediate subjective comfort. Controlled studies using standardized outcome measures are warranted. Full article

Although Simarouba glauca DC. has been recognized for its therapeutic properties, its anticancer effects against oral cancer have not been adequately investigated. The present study aimed to evaluate the activity of S. glauca leaf extracts against oral squamous cell carcinoma (OSCC). S. glauca leaves were extracted using solvents of increasing polarity, and the resulting fractions were evaluated for their phytochemical composition, antioxidant activity, and cytotoxic effects. Among all extracts, the S. glauca hexane extract (SGHE) exhibited the most potent anticancer activity against cell lines representing OSCC (CAL-27), cervical cancer (HeLa), and mouse mammary tumors (4T1). Bioactivity-guided fractionation identified D-erythro-Sphinganine as a major constituent present in hexane extract, possibly contributing to anticancer activity. But since the anticancer activity of crude hexane extract is superior compared to isolated D-erythro-Sphinganine, we predict a synergistic interaction among the multiple bioactive compounds present in the crude hexane extract. Hence, further studies were carried out with crude hexane extract. Mechanistic studies have shown that the anticancer activity of hexane extract is due to its ability to (a) alter cell cycle progression, (b) trigger apoptosis, and (c) inhibit cell migration in CAL-27 cells. Overall, these findings indicate that the hexane extract of S. glauca leaf possesses multi-target anticancer potential and warrants further mechanistic and in vivo investigations. Full article

Background: Early and accurate diagnosis remains crucial to improving outcomes in oral cancer. Optical coherence tomography (OCT) offers real-time, high-resolution imaging that may support diagnosis and treatment planning in oral squamous cell carcinoma (OSCC). Methods: In this prospective study, preoperative OCT scans were obtained from 68 histologically confirmed OSCC lesions, with 30 paired adjacent mucosa samples from the same patients as histologically negative comparators (diagnostic dataset: 98 lesions). OCT findings were compared with histopathology for diagnostic performance, OCT biomarker patterns by tumour grade, tumour depth measurement, margin assessment, and subsite-specific performance. Results: OCT demonstrated 98.5% sensitivity, 96.7% specificity, and an AUC of 0.98 for detection of invasive OSCC. OCT biomarkers—including abnormal epithelial architecture with variable epithelial thickness, stratification loss, basement membrane disruption, and increased subepithelial reflectivity—varied systematically with tumour differentiation grade. Tumour depth measurements showed acceptable agreement with histology, while margin definition was correct in 80% of cases. Performance was highest in the tongue and the floor of the mouth, with reduced performance in posterior/keratinised subsites. Image artefacts occurred in 5.1% of scans. Conclusions: OCT provides a reproducible, real-time adjunct for diagnosis, margin planning, and lesion stratification in OSCC, with recognised limitations related to light attenuation and operator-dependent factors. Multicentre validation and integration with digital interpretation platforms are warranted. Full article

5-Aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT) is one of the treatment modalities for oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC). However, the role of ferroptosis in ALA-PDT for OLK and OSCC remains unclear. Therefore, this study aimed to investigate whether ALA-PDT can induce ferroptosis in OLK and OSCC. We detected relative cellular dehydrogenase activity (CCK-8 assay), long-term proliferative viability, reactive oxygen species (ROS) generation, glutathione levels, and mitochondrial morphology after ALA-PDT. The expression of ferroptosis-related proteins was detected using Western blot. A tongue OSCC model was established in male BalB/c nude mice, and then ALA-PDT was performed. Immunohistochemical staining of Ki67, GPX4 and FTH1 was conducted to evaluate the effect of ALA-PDT. Subsequently, OLK and OSCC cells were pre-treated with ferrostatin-1 (Fer-1) before ALA-PDT. Relative cellular dehydrogenase activity, ROS generation, lipid peroxidation, Fe²⁺ levels, and ferroptosis-related protein expression were measured. Finally, OLK and OSCC cells were treated with a combination of ALA-PDT and erastin, and mitochondrial function was evaluated. In vitro study showed that ALA-PDT increased ROS generation and decreased GSH/GSSG ratio in OLK and OSCC cells. After ALA-PDT, mitochondrial morphology exhibited typical characteristics of ferroptosis. In vivo experiments showed that immunohistochemistry (IHC) scores of Ki67, GPX4 and FTH1 in the tissues decreased after ALA-PDT. Moreover, pre-treatment with Fer-1 could reverse ROS levels, lipid peroxidation and intracellular Fe²⁺ accumulation in OLK and OSCC cells after ALA-PDT. Additionally, Fer-1 pre-treatment reversed the changes in protein expression induced by ALA-PDT. The combination of ALA-PDT and erastin significantly reduced mitochondrial O₂•⁻ production and decreased mitochondrial membrane potential. Above all, ALA-PDT can induce ferroptosis in OLK and OSCC. The use of ferroptosis agonists may enhance the therapeutic efficacy of ALA-PDT for OLK and OSCC. Full article

Background/Objectives: The pattern of invasion describes the arrangement of neoplastic cells along the tumor infiltrative front and refers to the way cancer infiltrates tissue at the tumor/host interface. Accumulating evidence suggested that the Worst Pattern of Invasion (WPOI) represents an independent prognostic factor in oral squamous cell carcinoma (OSCC). However, it is still considered a minor prognostic criterion, and it is recommended as an optional report component in the College of American Pathologists (CAP) guideline. Methods: Therefore, the study aims to extensively review the literature data regarding the prognostic role of the WPOI in OSCC. Results: The WPOI resulted as an independent prognostic factor for locoregional recurrences (LRRs), lymph node metastasis (LMN), overall survival (OS), disease-specific survival (DSS), and bone tissue infiltration, regardless of the oral subsite and the pathological stage. Moreover, several authors suggested the evaluation of the WPOI to lead the postoperative management and to determine the occult LNM in early-stage OSCC. Conclusions: The prognostic relevance of the WPOI in OSCC highlights its evaluation in pathological daily practice. Therefore, the WPOI-detection method and scoring system should be validated based on the tumor stage and site. Full article

Oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge due to aggressive progression, high recurrence, and limited selectivity of current treatments. In this study, a series of seven 4-amino-2-substituted tetrahydrobenzothieno[2,3-d]pyrimidines were evaluated for their cytotoxic, antiproliferative, and mechanistic effects against oral cancer cell lines with different metastatic potential (HSC-3 and SCC-9), alongside non-tumorigenic keratinocytes (HaCaTs). Several compounds demonstrated selective anticancer activity, with Compounds 5 and 6 showing the most favorable balance between potency and selectivity. Antiproliferative assays revealed effective inhibition of cancer cell growth, while clonogenic assays confirmed a pronounced reduction in long-term survival, particularly in highly metastatic HSC-3 cells. Mechanistic studies indicated that the anticancer effects are associated with S-phase cell cycle arrest, apoptosis induction, and profound disruption of the actin cytoskeleton. In silico ADME and drug-likeness analyses supported the lead-like properties of the most active derivatives. Overall, these findings identify thienopyrimidine derivatives as promising scaffolds for the development of targeted therapies against OSCC and warrant further optimization and in vivo evaluation. Full article

The tightly controlled and transient acquisition of a motile phenotype by otherwise static epithelial cells (epithelial–mesenchymal transition, EMT) enables the repair of a damaged epithelium. Conversely, a persistent, dysregulated, and exacerbated EMT characterizes epithelial malignancies such as breast carcinoma (BC) and oral squamous cell carcinoma (OSCC), being key for their metastasis and for their escaping anti-tumor immune responses. Herein, we investigated the relationship between EMT signatures and immune cell infiltration across OSCC and metastatic BC with the aim to identify prognostic markers and/or therapeutic targets common to both these malignancies, or unique to OSCC or BC. To this end, we analyzed publicly available transcriptomic datasets to identify coding genes involved in EMT with strong correlation to immune cell signatures. The methodology consisted of data selection, correlation analysis, signature overlap determination, and validation using independent databases. Results indicated that in both OSCC and BC the expression of EMT-related genes is strongly associated with that of immunosuppressive and pro-tumor macrophages. Notably, the FN1 gene coding for the extracellular matrix glycoprotein fibronectin (FN) emerged as the EMT gene common to either tumor types. In confirmation of this, FN protein levels were higher in OSCC and BC tissues than in their normal counterparts. Given FN capability of favoring tumor invasion and metastasis while hindering antitumor immune responses, these data encourage the development of FN antagonists to be used as an adjunct to conventional therapy in the treatment of both OSCC and BC. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) remains the seventh most common cancer worldwide, characterized by late-stage diagnosis and poor 5-year survival rates. Oral squamous cell carcinoma (OSCC) is the most prevalent subtype. The identification of robust diagnostic, prognostic, and predictive markers is essential for personalized treatment monitoring. Methods: Following PRISMA and PICO standards, we conducted a comprehensive review of studies published over the past 10 years across PubMed/MEDLINE, Scopus, and Web of Science. The selection process was facilitated by AI-powered tools (Rayyan QCRI), and study quality was assessed using NOS or QUIPS. Results: 34 articles (including meta-analyses and original trials) were identified. Established clinical markers, such as p16-positivity (HR ≈ 0.55) and PD-L1 (CPS), remain significant. However, the molecular landscape is expanding to include high-risk lncRNA signatures (HR ≈ 2.50), immune checkpoints such as TIGIT (HR ≈ 1.85), and genomic alterations, including IL-10 promoter polymorphisms. We highlight that epigenetic silencing of p16 affects only about 25% of patients, while metabolic regulators (e.g., GLUT-1) and protein markers (e.g., MASPIN) offer critical predictive value for therapy response. Conclusions: The diagnostic and predictive paradigm is shifting toward a multi-omic approach that integrates DNA, RNA, proteins, and metabolic indicators. Future clinical use will rely on AI-driven multimarker panels and non-invasive liquid biopsies to enable real-time monitoring and de-escalation of treatment strategies. Full article

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

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