Search Results (84)

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

Extracellular traps (ETs) are immune-derived chromatin networks initially described as antimicrobial barriers but increasingly recognized as modulators of tissue homeostasis and autoimmunity. The oral mucosa, constantly exposed to inflammatory stimuli, is particularly sensitive to ET-mediated remodeling (extracellular traps-mediated remodeling). In this study, we investigated how platelet-rich plasma (PRP), platelet-poor plasma (PPP), and washed platelets (WPT), widely used in regenerative medicine, influence ETosis in monocytes and macrophages, and how these ETs modulate the responses of primary buccal keratinocytes (pBMKs). ETs were induced in monocytes/macrophages using PRP, PPP, and WPT. pBMKs were exposed to ET-rich supernatants, and proliferation was monitored in real time through a live cell imaging system. ETs derived from PRP, PPP, and WPT did not induce either a statistically significant proliferation or morphological changes in buccal keratinocytes. These findings suggest that both platelet-derived products (PRP, PPP, WPT) and ETs play a crucial role in modulating epithelial biology, thus suggesting their possible role in chronic autoimmune diseases characterized by persistent inflammation and epithelial remodeling. Full article

Background/Objective: Buccal delivery offers a potential route to circumvent gastrointestinal degradation and hepatic first-pass metabolism, but hydrophilic peptides typically exhibit limited mucosal permeation. Nanostructured lipid carriers (NLCs) have been proposed as delivery platforms capable of modulating interfacial interactions and improving mucosal transport. This study aimed to quantitatively evaluate the ex vivo buccal permeation of angiotensin II (Ang II), used as a hydrophilic peptide model, when associated with NLCs compared with free peptide under matched Franz diffusion cell conditions. Methods: Ang II-associated NLCs were prepared by melt emulsification combined with a low-energy injection technique. Particle size, polydispersity index, and zeta potential were determined by dynamic light scattering and laser Doppler electrophoresis. Association efficiency and drug loading were quantified by indirect spectrofluorometric analysis. Ex vivo permeation studies were conducted using porcine buccal mucosa mounted in Franz diffusion cells, and cumulative permeation, steady-state flux, and apparent permeability coefficients were calculated. Results: The NLCs exhibited nanometric size, moderate polydispersity, and association efficiency above 80%, and remained colloidally stable at 4 °C for 28 days. In ex vivo experiments, Ang II-associated NLCs showed measurable cumulative permeation, reaching approximately 9% after 2 h, whereas free Ang II was not detected in the receptor compartment under the tested conditions. Conclusions: This work provides a quantitative ex vivo buccal transport comparison of a hydrophilic peptide model delivered as NLC-associated versus free peptide under matched Franz cell conditions. The findings support further investigation of NLC-based approaches for buccal delivery of vasoactive peptides and provide a rational basis for future in vivo evaluation of mucosal delivery performance and systemic exposure. 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: Ameloblastomas account for roughly 1% of all jaw tumours and cysts, typically manifesting as slow-growing, painless swellings that expand both buccal and lingual cortical plates and may infiltrate adjacent soft tissue, often leading to a delayed diagnosis. These benign tumours, characterized by local invasiveness, originate from epithelial tissues and may develop from dental lamina cell rests, the enamel apparatus, the epithelial lining of odontogenic cysts, or basal epithelial cells of the oral mucosa. Methods: This paper aims to describe the comprehensive and interdisciplinary management of an extensive ameloblastoma in a 16-year-old patient, emphasizing the diagnostic challenges, surgical resection, reconstructive procedures, and subsequent oral rehabilitation. Results: At the eleven-year follow-up, clinical and radiographic examinations showed no signs of tumour recurrence. The patient presented no symptoms, indicating neither pain nor functional impairment. The prosthetic rehabilitation utilizing implant-supported fixed restorations was successfully completed, resulting in satisfactory masticatory function and aesthetics. This case adds to the existing evidence on the management of extensive ameloblastomas by demonstrating successful long-term outcomes following interdisciplinary surgical reconstruction and rehabilitation. Conclusions: The presented case highlights the complexity of restoring the lost tissues and functions, as well as the long-term clinical, functional, and aesthetic outcomes over an eleven-years follow-up period. Full article

Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life. Full article

In pathology laboratories, several volatile organic compounds (VOCs) are used, such as formaldehyde, ethanol, and xylene. These substances are recognized as genotoxic and cytotoxic, which is why their handling poses risks to human health. The buccal micronucleus (MN) cytome assay is a non-invasive, useful, and simple method to detect these effects in exposed individuals. The aim of the study was to evaluate the risk of genotoxicity and cytotoxicity of VOCs in pathology professionals of S. Miguel Island, Azores, Portugal. The study comprised two groups: exposed workers (n = 21) from the three laboratories of S. Miguel, and a reference group (n = 50), randomly chosen from other hospital services without known exposure to VOCs. The exfoliated buccal cells were auto-sampled by all the participants using a cytobrush. The samples were processed in ThinPrep^®, stained with modified Feulgen with Fast Green, and visualized for MN and other nuclear anomalies (ONAs), such as karyorrhexis, pyknotic, and karyolytic cells. Results showed that VOCs have a predictive significance for MN frequency, leading to the conclusion that their exposure is an increased risk factor for the health of these professionals, approximately four times greater than in the control group. Full article

Background/Objectives: Oral lichen planus (OLP) is a chronic inflammatory mucocutaneous disorder with a recognized potential for malignant transformation. While histopathological examination remains the diagnostic gold standard, mucoscopy has emerged as a valuable non-invasive tool for assessing striae patterns, vascular features, and pigmentary alterations. This study aimed to evaluate the mucoscopic characteristics of OLP across different oral mucosal sites and to compare them with other inflammatory oral conditions, assessing their diagnostic relevance. Methods: A retrospective comparative study was conducted on 106 patients, including 33 with histopathologically confirmed OLP and 73 with other inflammatory oral conditions (pemphigus vulgaris, chronic cheilitis, hyperplastic oral candidiasis, leukoplakia, squamous cell carcinoma, pachyonychia congenita, morsicatio buccarum). Mucoscopic evaluation focused on the buccal mucosa, vermilion, and lingual mucosa. Features assessed included background color, white striae patterns, vascular morphology, the presence of erosions, and other features like blunting of the lingual papillae and scales on the vermilion. Statistical analysis was carried out using SPSS 29.0. Results: Reticular striae were highly specific to OLP, particularly on the buccal mucosa (90.9%, p < 0.001). Leukoplakia-like lesions were most prevalent on the lingual mucosa and significantly associated with dotted (p = 0.027) and looped vessels (p = 0.002). Erosions correlated significantly with both dotted (p < 0.001) and linear vessels (p = 0.011), especially in lingual and vermilion lesions. In comparison, control group lesions displayed significantly more globular structures (p < 0.001), veil-like patterns (p < 0.001), and diffuse vascular distributions (p = 0.018), particularly in cheilitis and candidiasis cases. Conclusions: Mucoscopy reveals distinct site-specific patterns in OLP, supporting its role as a non-invasive diagnostic aid. Comparative analysis highlights its utility in differentiating OLP from other inflammatory oral conditions and in identifying lesions with features suggestive of malignant potential. These findings support the integration of mucoscopy into routine clinical practice and warrant further validation through larger, prospective studies. Full article

Background and Clinical Significance: Renal cell carcinoma (RCC) is the third most common cancer that metastasizes to the oral and maxillofacial region following breast and lung cancers. Metastatic involvement in the oral cavity is rare and can present as a diagnostic challenge due to non-specific clinical features that mimic other benign or malignant conditions. The limited information available regarding oral metastasis of RCC highlights the importance of recognizing this uncommon presentation. Case Presentation: A 50-year-old female presented with a painful swelling in the buccal and palatal mucosa of the right maxilla that progressively enlarged over several months. Initially, this lesion was diagnosed clinically as a pyogenic granuloma. However, given the lesion’s continued growth and unusual presentation, a biopsy was performed. Histopathological examination confirmed the lesion as metastatic renal clear-cell carcinoma (ccRCC), with immunohistochemical analysis verifying the renal origin. Further diagnostic tests, including a computed tomography (CT) urogram, chest CT, and bone scintigraphy, revealed additional metastases in the left adrenal gland, lungs, and bone. Conclusions: This case is notable because the oral lesion was the first visible sign of RCC, making it a rare presentation of metastatic RCC. This underscores the importance of thorough history taking, detailed clinical evaluations, and considering rare metastatic conditions in the differential diagnosis of oral swellings. Additionally, this case reinforces the significance of routine cancer screenings for early detection of undiagnosed cancer. We also updated a previous literature review of metastatic RCC to the head and neck region, covering cases until 2023. Full article

Despite MCT oil’s potential antimicrobial benefits for gastrointestinal health, its effects on disrupting cariogenic pathogens on oral mucosal surfaces remain underexplored. This study evaluated the impact of MCT oil on the adhesion and invasion of Candida albicans and Streptoccocus mutans using planktonic and mucosal models. First, a planktonic model was used to assess the impact of various concentrations of MCT on the growth of S. mutans and C. albicans. Subsequently, a mucosal model was established by seeding TR-146 human buccal mucosal epithelial cells on a 3 µm porous transwell membrane, forming an epithelial barrier. MCT oil was then applied to the epithelial barriers in different durations (10, 30, and 60 min). Subsequently, C. albicans and S. mutans were introduced in the transwell and their adherence to the epithelial cells and their transmigration through the barriers was assessed using colony-forming unit counts and the barrier integrity was assessed by trans epithelial electrical resistance (TEER). Furthermore, cytotoxicity of MCT oil on mucosal cells was assessed by AlamarBlue assay. We found that higher MCT concentrations (90% and 100%) significantly inhibited C. albicans and S. mutans growth in planktonic conditions. Additionally, MCT oil reduced S. mutans adhesion to epithelial cells, highlighting its potential to interfere with bacterial attachment and colonization to oral mucosa. However, the oil had limited effects on C. albicans adhesion and transmigration. MCT demonstrated no cytotoxic effects on the viability of epithelial cells. The study findings highlight the potential benefits of MCT oil, particularly in oral bacterial inhibition, for oral health applications. Full article

Grass carp (Ctenopharyngodon idella) is a Cyprinid fish of aquacultural and research importance. The buccal cavity represents the gateway of the digestive tract. The present study investigated the adaptational changes involving various components of the buccal cavity of fingerling (three months posthatching, mph), yearling (12 mph), and adult (48 mph) C. idella using scanning electron microscopy, histology, and morphometry. The upper and lower lips appeared uninterrupted at the three studied stages and were limited caudally by the upper and lower jaws. The jaw epithelium was the thickest part of the buccal epithelium; ultrastructurally, it appeared smooth with ridge-like borders in fingerlings that transformed into microgrooves in yearlings. In adult C. idella, the jaw mucosa was organized into dome-shaped masses separated from each other by tight furrows. Each mass was formed from several keratinocytes with corrugated surfaces that featured numerous microdepressions. Except for the jaws, taste buds, mainly of type I, and acidic and neutral goblet cells were observed throughout the mucosa of the buccal cavity, and their densities were highest along the mucosal folds of the palate and oral floor, suggesting a principal role for these parts in both gustation and food lubrication. This study is the first to report age-associated spatiotemporal changes in the buccal cavity of grass carp and will serve as a fundamental reference during the interpretation of various types of oral pathologies in teleost. Full article

The progressive aging of the global population and the high impact of neurodegenerative diseases, such as Alzheimer’s disease (AD), underscore the urgent need for innovative diagnostic and therapeutic strategies. AD, the most prevalent neurodegenerative disorder among the elderly, is expected to affect 75 million people in developing countries by 2030. Despite extensive research, the precise etiology of AD remains elusive due to its heterogeneity and complexity. The key pathological features of AD, including amyloid-beta plaques and hyperphosphorylated tau protein, are established years before clinical symptoms appear. Recent studies highlight the pivotal role of neuroinflammation in AD pathogenesis, with the chronic activation of the brain’s immune system contributing to the disease’s progression. Pro-inflammatory cytokines, such as TNF-$\alpha$, IL-1$\beta$, and IL-6, are elevated in AD and mild cognitive impairment (MCI) patients, suggesting a strong link between peripheral inflammation and CNS degeneration. There is a pressing need for minimally invasive, cost-effective diagnostic methods. Buccal mucosa cells and saliva, which share an embryological origin with the CNS, show promise for AD diagnosis and prognosis. This study integrates cellular observations with advanced data processing and machine learning to identify significant biomarkers and patterns, aiming to enhance the early diagnosis and prevention strategies for AD. Full article

Purpose: The purpose of this study is to assess the effectiveness of the best performing interpretable machine learning models in the diagnoses of leukoplakia and oral squamous cell carcinoma (OSCC). Methods: A total of 237 patient cases were analysed that included information about patient demographics, lesion characteristics, and lifestyle factors, such as age, gender, tobacco use, and lesion size. The dataset was preprocessed and normalised, and then separated into training and testing sets. The following models were tested: K-Nearest Neighbours (KNN), Logistic Regression, Naive Bayes, Support Vector Machine (SVM), and Random Forest. The overall accuracy, Kappa score, class-specific precision, recall, and F1 score were used to assess performance. SHAP (SHapley Additive ExPlanations) was used to interpret the Random Forest model and determine the contribution of each feature to the predictions. Results: The Random Forest model had the best overall accuracy (93%) and Kappa score (0.90). For OSCC, it had a precision of 0.91, a recall of 1.00, and an F1 score of 0.95. The model had a precision of 1.00, recall of 0.78, and F1 score of 0.88 for leukoplakia without dysplasia. The precision for leukoplakia with dysplasia was 0.91, the recall was 1.00, and the F1 score was 0.95. The top three features influencing the prediction of leukoplakia with dysplasia are buccal mucosa localisation, ages greater than 60 years, and larger lesions. For leukoplakia without dysplasia, the key features are gingival localisation, larger lesions, and tongue localisation. In the case of OSCC, gingival localisation, floor-of-mouth localisation, and buccal mucosa localisation are the most influential features. Conclusions: The Random Forest model outperformed the other machine learning models in diagnosing oral cancer and potentially malignant oral lesions with higher accuracy and interpretability. The machine learning models struggled to identify dysplastic changes. Using SHAP improves the understanding of the importance of features, facilitating early diagnosis and possibly reducing mortality rates. The model notably indicated that lesions on the floor of the mouth were highly unlikely to be dysplastic, instead showing one of the highest probabilities for being OSCC. Full article

Background: Metastatic tumors of the oro-facial tissuesare rare, with an incidence ranging between 1% and 8% of all oral malignant tumors. Generally reported with a peak of incidence in the 5–7th decades but possibly occurring at any age, metastases may represent the first sign of an occult cancer or manifest in patients with an already known history of a primary carcinoma, mostly from the lungs, kidney, prostate, and colon/rectum in males, and the uterus, breast, lung, and ovary in females. In the oro-facial tissues, the most involved sites are the oral mucosa, gingiva/jawbones, tongue, and salivary glands. Methods: A broad and deep literature review with a comprehensive analysis of the existing research on oro-facial metastases from renal-cell carcinoma (RCC) was conducted by searching the most used databases, with attention also paid to the clear-cell histological variant, which is the most frequent one. Results: Among the 156 analyzed studies, 206 cases of oro-facial metastases of renal cancer were found in patients with an average age of 60.9 years (145 males, 70.3%; 61 females, 29.6%). In almost 40% of the cases, metastasis represented the first clinical manifestation of the primary tumor, and 122 were histologically diagnosed as clear-cell renal-cell carcinoma (ccRCC) (59.2%). The tongue was involved in most of the cases (55 cases, 26.7%), followed by the gingiva (39 cases, 18.9%), mandible (35 cases, 16.9%), maxilla (23 cases, 11.1%), parotid gland (22 cases, 10.6%), buccal mucosa (11 cases, 5.3%), lips (7 cases, 3.3%), hard palate (6 cases, 2.8%), soft palate, masticatory space, and submandibular gland (2 cases, 0.9%), and lymph nodes, tonsils, and floor of the mouth (1 case, 0.4%). Among the 122 ccRCCs (84 males, 68.8%; 38 females, 31.1%), with an average age of 60.8 years and representing in 33.6% the first clinical manifestation, the tongue remained the most frequent site (31 cases, 25.4%), followed by the gingiva (21 cases, 17.2%), parotid gland (16 cases, 13.1%), mandibular bone (15 cases, 12.2%), maxillary bone (14 cases, 11.4%), buccal mucosa and lips (6 cases, 4.9%), hard palate (5 cases, 4%), submandibular gland and soft palate (2 cases, 1.6%), and lymph nodes, tonsils, oral floor, and masticatory space (1 case, 0.8%). The clinical presentation in soft tissues was mainly represented by a fast-growing exophytic mass, sometimes accompanied by pain, while in bone, it generally presented as radiolucent lesions with ill-defined borders and cortical erosion. Conclusions: The current comprehensive review collected data from the literature about the incidence, site of occurrence, age, sex, and survival of patients affected by oro-facial metastases from renal-cell carcinoma, with particular attention paid to the cases diagnosed as metastases from clear-cell renal-cell carcinoma, which is the most frequent histological variant. Clinical differential diagnosis is widely discussed to provide clinicians with all the useful information for an early diagnosis despite the effective difficulties in recognizing such rare and easily misdiagnosed lesionsTheir early identification represents a diagnostic challenge, especially when the clinical work-up is limited to the cervico–facial region. Nevertheless, early diagnosis and recently introduced adjuvant therapies may represent the key to better outcomes in such patients. Therefore, general guidelines about the clinical and radiological identification of oro-facial potentially malignant lesions should be part of the cultural background of any dentist. Full article

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain–Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases. Full article