Search Results (246)

Background/Objectives: This study aimed to explore the potential value of narrow-band-imaging (NBI)-derived mean optical intensity (MOI) in monitoring the progression of oral squamous cell carcinoma (OSCC), from the normal oral mucosa through epithelial dysplasia to invasive carcinoma. We compared differences in the NBI MOI among distinct pathological stages, so as to provide preliminary evidence for its clinical application in auxiliary diagnosis and progression assessment for OSCC. Methods: A total of 40 human oral mucosal specimens (15 normal, 15 oral leukoplakia, 10 OSCC) were enrolled for NBI image acquisition and MOI measurements. A 4-nitroquinoline-1-oxide (4NQO)-induced mouse OSCC model (n = 34) was used to dynamically record MOI changes across different pathological stages. A syngeneic tongue tumor mouse model (n = 16) was further established to evaluate whether MOI could reflect tumor formation and growth. All MOI values were quantified using ImageJ software with standardized region-of-interest (ROI) selection and background correction. Results: In clinical samples, MOI values decreased progressively from the normal mucosa (129.6 ± 5.991 arbitrary units (a.u.)) to oral leukoplakia (OLK) subgroups, including mild dysplasia (104.6 ± 3.757 a.u.) and moderate-to-severe dysplasia (91.77 ± 4.345 a.u.), and further to OSCC (54.41 ± 14.40 a.u.). In the 4NQO model, the MOI of the lingual mucosa was highest in the healthy control group (167.3 ± 10.05 a.u.) and gradually declined with increasing dysplasia severity, reaching the lowest level at the OSCC stage (48.67 ± 10.07 a.u.). In the syngeneic tumor model, the MOI was significantly lower in tumor-bearing mice than in healthy controls (47.85 ± 10.44 a.u. vs. 119.7 ± 14.20 a.u., p < 0.001). Receiver operating characteristic (ROC) analysis demonstrated good diagnostic performance of the MOI in distinguishing healthy tissue from cancerous lesions. Conclusions: NBI-derived MOI may quantitatively reflect the dynamic alterations of the oral mucosa during oral carcinogenesis and could represent a potential biomarker enabling the non-invasive, repeatable early evaluation and dynamic monitoring of OSCC. Full article

Oral squamous cell carcinoma (OSCC), comprising ~90% of oral malignancies, remains a major global health burden with rising incidence despite declining tobacco use. While tobacco and alcohol are classic dominant risk factors, a distinct subgroup of nonsmoking, nondrinking (NSND) patients is increasingly recognized, accounting for 15–35% of OSCC cases in many cohorts, particularly in developed countries. This emerging epidemic shows striking demographic patterns: strong female predominance (often 65–77% of cases), bimodal age distribution with peaks in young adults (<45 years) and elderly individuals (>70 years), and overrepresentation among non-Hispanic White and certain Asian populations. Unlike traditional habit-related OSCC, which favors the floor of the mouth in older males, NSND tumors predominantly arise on the lateral tongue, gingiva, and buccal mucosa. Etiopathogenesis extends far beyond conventional carcinogens and involves multifactorial mechanisms, including chronic mechanical irritation from dental factors, oral microbiome dysbiosis enriched with periodontal pathogens (e.g., Fusobacterium nucleatum and Porphyromonas gingivalis), limited roles for viruses (minimal HPV contribution, possible EBV or “hit-and-run” HSV effects), genetic susceptibilities (e.g., Fanconi anemia and CDKN2A mutations), epigenetic changes, hormonal influences contributing to female bias, metabolic conditions (diabetes and hyperlipidemia), poor oral hygiene, and chronic inflammation. NSND OSCC frequently exhibits a distinct immunological profile with higher tumor-infiltrating lymphocytes and PD-L1 expression, potentially favoring immunotherapy, though prognosis remains heterogeneous—better in some cohorts due to fewer comorbidities, yet worse in young patients with higher recurrence and second primary tumor risks. Delayed diagnosis is common due to low suspicion in “low-risk” individuals. This review underscores NSND OSCC as a unique entity requiring expanded risk assessment, heightened clinical vigilance for persistent oral lesions regardless of habit history, and targeted research into novel prevention and therapeutic strategies. Full article

Background and Objectives: This study aimed to detect and genotype human papillomavirus (HPV) in tissues from oral squamous cell carcinoma (OSCC), oral potentially malignant disorders (OPMD), and healthy individuals. Materials and Methods: The study included 60 patients (31 men and 29 women; median age 60 years, IQR 41.5–69.8) admitted to the Department of Dental, Oral and Maxillofacial Surgery, Medical University of Sofia. Patients were divided into three groups: healthy oral mucosa (n = 20), OPMD (n = 20), and OSCC (n = 20). HPV was tested using punch biopsies with nested PCR and chip technology. Results: Low-risk HPV was found in four (20%) healthy individuals (types 6/11, 43), seven (35%) OPMD patients (types 6/11, 42, 43), and eleven (55%) OSCC patients (types 6/11, 42, 43). Pairwise comparison showed a significant difference in HPV positivity between healthy individuals and OSCC patients (p = 0.022). Among all HPV-positive OPMDs, the virus was detected in two leukoplakia cases (28.6%), three lichen planus cases (42.9%), one lichenoid lesion case (14.3%), and one proliferative verrucous leukoplakia case (14.3%). According to binary logistic regression, OSCC patients were 4.9 times more likely to be HPV-positive compared to healthy individuals (p = 0.027). Conclusions: HPV infection may play a potential role in the pathogenesis of OPMD and OSCC. Full article

Oral candidiasis (OC) is the most frequent fungal infection among users of dental prosthetic devices, immunocompromised patients, and those who underwent chemotherapy treatment and had a complication of long-term antibiotic therapy. About 150 species of Candida fungi have been described, whereas over 80% of oral fungal infections are attributed to the opportunistic pathogen Candida albicans. Pain, dryness of oral mucosa, pathological lesions, and intermittent mucosal bleeding are the main symptoms that worsen the daily functioning of the abovementioned fungal-infected patients. A promising adjunctive strategy may involve the use of probiotic bacteria to attenuate fungal colonization in the oral cavity in order to reduce the need for conventional treatment, which carries a risk of antifungal drug resistance—a significant problem worldwide. Probiotic formulations mostly incorporate commensal bacteria that naturally inhabit oral ecosystems such as Lactobacillus spp., Bifidobacterium spp., Bacillus spp., and others. Probiotic organisms may contribute to the restoration of oral microbiome homeostasis through numerous mechanisms, such as competitive control of Candida species numbers, better adhesion to oral mucosa and production of bioactive compounds and antimicrobial metabolites. Despite many studies, the current evidence base remains heterogeneous. Well-designed studies across diverse populations are required to determine whether probiotic-based interventions can be an effective and clinically useful alternative or adjunct to standard antifungal therapy of OC. Full article

Background: Oral lipomas are uncommon benign tumors composed of mature adipocytes, accounting for roughly 1% of benign intraoral lesions. Common predilection sites are buccal mucosa, lips, and tongue, presenting as slow-growing, nodular masses, often with a yellow hue. As the size of most lesions does not exceed 10 mm, particularly larger lipomas may be misdiagnosed. We present two cases of large oral lipomas. Case reports: Case 1: A 58-year-old male with a painless, sessile nodular mass of approximately 2.5 cm in the left cheek, increasing in size and causing discomfort during mastication. After excision, histopathology revealed mature adipocytes with delicate fibrous septa. Case 2: A 47-year-old female with a tender yellow growth of approximately 2 cm in her lower lip, increasing in size and causing aesthetic problems with functional discomfort. After sharp dissection, the specimen presented acanthotic and parakeratotic epithelium with adipocytic tumorous tissue, permeated by collagenous cords. Conclusions: Oral lipomas are uncommon, mostly asymptomatic benign lesions. Mostly found in the buccal mucosa and lower lip, they can mimic more common growths. When located superficially, a conservative surgical excision leads to resolution with rare recurrences. Histopathological inspection is necessary to confirm the benign nature of the lesion. Full article

Inflammatory bowel disease (IBD)—including Crohn’s disease, ulcerative colitis, and indeterminate colitis—is a chronic immune-mediated condition that primarily affects the intestinal mucosa but often presents with extraintestinal digestive manifestations, which are important yet frequently underrecognized sources of morbidity. These heterogeneous manifestations reflect diverse genetic, microbial, immunologic, and environmental influences, highlighting the value of a personalized medicine approach. Hepatobiliary involvement affects IBD adults patients and is even more common in children, ranging from mild liver enzyme elevations to severe complications such as liver failure, with autoimmune disorders, cholelithiasis, portal vein thrombosis, and non-alcoholic fatty liver disease as key considerations. Pancreatic manifestations may include autoimmune or acute pancreatitis, often linked to gallstones, thiopurine exposure, or duodenal Crohn’s disease, while splenic abnormalities, such as granulomatous lesions, splenomegaly, or functional hyposplenism, reflect systemic immune dysregulation. Oral findings—including aphthous ulcers, periodontitis, pyostomatitis vegetans, and granulomatous cheilitis—can serve as early, patient-specific indicators of disease activity. Personalized approaches, encompassing investigations tailored to the individual profile and selected targeted therapies, are essential for improving diagnostic accuracy, preventing complications, and optimizing multidisciplinary care in patients with IBD. Full article

The intestinal mucosal barrier is a layered structure comprising fundamental components that play important roles in regulating paracellular permeability. Disruption of intestinal barrier homeostasis predisposes to infections, mucosal damage, and metabolic and allergic diseases. To provide protection against potential damage to the intestinal mucosa, agents such as prebiotics and probiotics are recommended due to their ability to secrete components and metabolites (e.g., bacteriocins, organic acids, enzymes) that can exert beneficial biological effects. The aim of this study is to comprehensively investigate the effects of a postbiotic derived from Pediococcus acidilactici on healthy rat intestinal tissue. A total of 78 Wistar Albino rats were used in this study. Following compositional analysis of the postbiotic, the animals were administered the postbiotic orally via gavage for different durations (7, 14, 21, 28 days) and at different doses (250 mg/Kg, 500 mg/Kg, 1000 mg/Kg). Characterization of the produced postbiotic revealed a diverse spectrum of biologically active compounds, including organic acids, phenolics, and volatile compounds. Histopathological examination of intestinal sections (duodenum, jejunum, ileum, cecum, colon, and rectum) showed no pathological lesions in any of the experimental groups. Conversely, immunohistochemical analysis revealed that the postbiotic increased the expression of CLDN3, OCLN, ZO1, AQP4, and AQP8, proteins involved in intestinal permeability and fluid transport, in a dose-dependent manner. These results highlight the potential of Pediococcus acidilactici as a supportive agent in a range of intestinal pathologies, including major intestinal diseases such as Crohn’s disease, ulcerative colitis, and inflammatory bowel disease (IBD). Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs) remain major clinical challenges due to late diagnosis and limited prognostic markers. This study evaluated salivary interleukin-6 (IL-6) and cotinine as potential biomarkers for oral epithelial transformation and exposure to risk factors. Methods: From 267 individuals with histopathologically confirmed OPMDs or OSCC, 47 patients met the inclusion criteria and were enrolled (18 OPMDs, 29 OSCC). A control group comprised 40 individuals without oral mucosal pathology. Unstimulated saliva samples were collected and analyzed for IL-6 and cotinine concentrations. Biomarker levels were compared among groups and evaluated in relation to smoking exposure, alcohol use, and clinicopathological parameters. Results: Salivary IL-6 and cotinine levels differed significantly among groups (p < 0.05), with the highest concentrations observed in OSCC patients, intermediate levels in OPMDs, and the lowest levels in controls. Cotinine levels were significantly higher in smokers and individuals with greater tobacco exposure in both study groups, whereas IL-6 concentrations were not significantly associated with smoking or alcohol consumption. No correlation between IL-6 and cotinine was found in OPMDs or OSCC; however, a moderate negative correlation was observed in controls. Conclusions: Salivary IL-6 and cotinine demonstrate potential as complementary, non-invasive biomarkers for assessing oral epithelial transformation and tobacco exposure. Their combined evaluation may support risk stratification and early detection in patients with OPMDs. Full article

Background/Objectives: This study aimed to quantitatively assess site-specific mean autofluorescence intensity across normal oral mucosal subsites and to evaluate the effectiveness of Autofluorescence Imaging (AFI) as an adjunct tool for distinguishing benign lesions, OPMDs, and oral cancers by comparing lesion intensity with anatomically matched healthy subsites. Methods: This observational study employed dual-mode imaging, comprising paired White Light Imaging (WLI) and AFI, captured from different oral cavity subsites using a smartphone-based point-of-care device. The Region of Interest (ROI) was annotated on WLI and automatically mapped to the corresponding AFI for both normal mucosa and lesions. WLI and AFI images were separated into their constituent red, green, and blue (RGB) channels, and AFI intensity was quantified via ImageJ. Results: A total of 1380 dual-mode images were acquired from 86 healthy participants. AFI intensities were comparable across most oral subsites, except for the lateral and ventral tongue. The lateral border showed the lowest fluorescence (Green channel-GC: 68.12 ± 28.27; Blue channel-BC: 25.29 ± 7.93), whereas the ventral tongue showed the highest (GC: 98.89 ± 42.22; BC: 37.08 ± 11.04; both p < 0.001). Among 611 lesions, predominantly from the buccal mucosa, AFI intensity declined progressively with increasing disease severity. Homogeneous leukoplakia (n = 149; GC: 38.62 ± 25.05; BC: 21.60 ± 9.50), non-homogeneous leukoplakia (n = 25; GC: 30.42 ± 18.66; BC: 18.25 ± 7.17) and oral cancer (n = 21; GC: 23.39 ± 15.53; BC: 15.82 ± 7.15; all p < 0.001) showed markedly reduced fluorescence, while benign lesions (n: 44; GC: 66.99 ± 30.88; BC: 32.01 ± 13.62) exhibited intermediate intensities, supporting AFI’s discriminative potential. Conclusions: This phase-1, proof-of-concept study highlights subsite-specific variations in autofluorescence intensity within healthy oral mucosa, providing an essential baseline for objective interpretation of lesion-associated fluorescence changes. AFI has the potential to be used as a non-invasive adjunct for monitoring OPMDs. Further validation in larger and more diverse cohorts is required before clinical implementation. Full article

Autoantibodies targeting α6β4 integrin have been identified in individual patients with mucous membrane pemphigoid (MMP). Reactivity against α6 integrin has been associated with oral lesions, while anti-β4 integrin reactivity has been linked to ocular involvement. However, the pathogenic effects of these antibodies have not been fully elucidated. Here, we investigated the pathogenic potential of anti-α6 and anti-β4 integrin IgG both in vitro and in vivo. Immune complexes of anti-α6 and anti-β4 integrin induced the release of reactive oxygen species from normal human leukocytes and stimulated CXCL2 secretion in cultured murine C5N keratinocytes. In vivo, repeated injections of IgG against a recombinant fragment of β4 integrin into C57BL/6 mice led to palpebral conjunctival swelling and mild oral lesions. The latter was observed following injection of IgG against a recombinant fragment of α6 integrin. Histopathological analysis revealed subepithelial inflammatory infiltrates without evidence of split formation. Direct immunofluorescence microscopy showed linear deposits of IgG at the basement membrane zone in most tissues, whereas C3 deposition was largely absent. This lack of complement activation was corroborated by a complement fixation assay, which confirmed that IgG against α6 and β4 integrin failed to induce C3 deposition in normal murine conjunctivae, buccal mucosa, or skin. Collectively, these findings indicate that IgG autoantibodies against α6 and β4 integrin exhibit pathogenic activity in vitro and induce mild disease in vivo, possibly due in part to relatively inefficient complement activation in this model. Full article

Chondrosarcoma of the maxillofacial skeleton is a rare malignant tumor characterized by cartilaginous differentiation and locally invasive growth. Diagnosis is particularly challenging in low-grade tumors because histological features often overlap with those of benign chondroma. We describe a 62-year-old woman with a recurrent cartilaginous tumor of the hard palate. After previous resections in 2013 and 2022, a third recurrence was detected. MRI showed a lobulated lesion at the anterior hard palate contiguous with the nasal septum. A two-staged treatment was performed, starting with a minimal invasive access Brown class 2a maxillectomy guided by a patient-specific cutting guide. Pending histological confirmation, an obturator prosthesis was placed to seal the oroantral communication. Histopathology confirmed a low-grade chondrosarcoma with clear margins of at least 5 mm. A second-stage reconstruction was performed a year later using a posterior pedicle lateral nasal wall flap (inferior turbinate flap) and palatal rotation flap restored nasal lining and oral mucosa. This approach achieved oncologic clearance with excellent functional outcomes. The case highlights the value of image-guided maxillectomy and staged regional flap reconstruction. Full article

NOTCH1 is associated with various tumors, including oral squamous cell carcinoma (OSCC), with a complex role depending on cellular contexts. Our aim was to analyze the expression of NOTCH1, several stem cell markers, and selected microRNAs in preneoplastic lesion of the oral cavity, oral epithelial dysplasia (OAD). Our study included formalin-fixed paraffin-embedded biopsy samples of 36 cases of OAD and 15 cases of normal oral mucosa. Expression of NOTCH1, stem cell markers (AGR2, KLF4, NANOG, OCT4, SOX2), and miR-27a, miR-34a, miR-128, miR-145, miR-150, and miR-335 was analyzed by quantitative PCR (qPCR). Expression of NOTCH1 protein was analyzed by immunohistochemistry. In OAD compared to normal mucosa, we found a significant increase in mRNA levels of NOTCH1, stem cell markers AGR2, NANOG, OCT4, and SOX2, and miR-150 and miR-128. NOTCH1 mRNA positively correlated with all five stem cell markers’ mRNA levels and miR-150. Immunohistochemistry showed variable expression patterns of NOTCH1 in OAD and normal mucosa. Our results support the role of NOTCH1 in early phases of OSCC development, with a potential contributory role in stemness, in association with AGR2, NANOG, OCT4, and SOX2, miR-150 and miR-128. These results support a complex role of NOTCH1 in carcinoma development, i.e., from oncogenic to tumor suppressor roles and stemness maintenance, not only in invasive OSCC but also in its precursor—OED. Full article

This case report presents a three-month follow-up of a patient who self-administered Melanotan II injections over a period of 64 days with the goal of achieving a deeper tanning effect. Melanotan II is an unlicensed synthetic peptide analog belonging to the melanocortin hormone family. It acts primarily by activating melanocortin 1 receptors on melanocytes, stimulating eumelanin production and resulting in skin pigmentation independent of sun exposure. Despite its popularity, particularly through promotion on social media, Melanotan II remains unregulated, and its use is associated with a range of potential adverse effects. During the initial intraoral examination, brown pigmentation was observed on the attached gingiva in both the maxillary and mandibular arches. The lesions were almost symmetrically distributed, with a more intense coloration in the anterior region of the lower jaw. Additional pigmented areas with irregular shapes and poorly defined borders were noted on the left and right buccal mucosa. At the one-month follow-up after discontinuation of the injections, the buccal mucosal pigmentation had nearly disappeared. However, at the three-month follow-up, gingival pigmentation persisted, though with visibly reduced intensity. To date, there is a lack of published data specifically addressing the timeline for resolution of oral pigmentation associated with Melanotan II use, making this case a valuable contribution to the limited existing literature on the subject. 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

Artificial Intelligence (AI) is a computer science that focuses on developing systems and machines capable of performing tasks that typically require human cognitive abilities. It has widespread applications in medical diagnostics. Its use has led to rapid advancements in diagnostic methodology, enabling the analysis of large datasets. The major applications of AI in medical diagnostics include personalized treatment based on patient genetics, preventive measures, and medical image analysis. AI is employed to analyse genomic data and biomarkers, aiding in the precise tailoring of therapies to individual patient needs. It could also be employed in modern dentistry in the near future, helping to achieve higher efficiency and accuracy in diagnosis and treatment planning. AI may be utilized in screening for oral mucosa lesions and to discriminate between oral potentially malignant disorders and cancers from benign lesions. The potential advantages of AI include high speed and accuracy in the diagnostic process, as well as relatively low costs. The aim of this review was to present the potential applications of AI methods in the diagnosis of selected mucocutaneous diseases. A literature review focuses on oral lichen planus, recurrent aphthous stomatitis, and oral and laryngeal leukoplakia. Full article