BACKGROUND: Oral squamous cell carcinoma (OSCC) requires reliable prognostic markers for treatment planning. Intratumoral budding (ITB) is a histopathological parameter shown to have prognostic relevance in several malig...BACKGROUND: Oral squamous cell carcinoma (OSCC) requires reliable prognostic markers for treatment planning. Intratumoral budding (ITB) is a histopathological parameter shown to have prognostic relevance in several malignancies. This study evaluated the prognostic utility of ITB in pre-operative OSCC biopsies compared with World Health Organization (WHO) histological grading. METHODS: An ambispective cohort of 42 pre-operative OSCC cases (well and moderately differentiated squamous cell carcinoma) with corresponding resection reports (January 2022-April 2025) was analyzed. ITB was assessed on hematoxylin and eosin-stained sections using International Tumor Budding Consensus Conference criteria, including TB0. Clinicopathological parameters and survival outcomes-disease-free survival (DFS) and overall survival (OS)-were evaluated. RESULTS: ITB positivity correlated significantly with higher nodal stage, tumor-node-metastasis stage, depth of invasion, perineural invasion, and extracapsular spread (all p < 0.05). ITB-positive cases showed reduced DFS (p = 0.023) and OS (p = 0.019), with worsening DFS across increasing ITB grades (p = 0.018). Cox regression demonstrated higher hazard ratios for ITB positivity (DFS: HR 47.93, 95% CI 0.12-18,571.86; OS: HR 49.80, 95% CI 0.14-18,238.87), though not statistically significant. WHO grading showed no significant survival associations. CONCLUSION: In this single-center, small cohort, ITB demonstrated stronger associations with adverse features and survival than WHO grading, warranting validation in larger cohorts.
OBJECTIVE: The clinical suspicion of a neoplastic lesion necessitates prompt diagnostic assessment through oral biopsy. However, the failure to accurately recognize an oral potentially malignant disorder (OPMD) or the mi...OBJECTIVE: The clinical suspicion of a neoplastic lesion necessitates prompt diagnostic assessment through oral biopsy. However, the failure to accurately recognize an oral potentially malignant disorder (OPMD) or the misdiagnosis of a benign lesion can lead to diagnostic delays with significant impact on the patient's health. This study aimed to evaluate the diagnostic accuracy of clinical diagnosis compared to the histopathological diagnosis, focusing on OPMDs and suspected benign lesions in an Italian university hospital. METHODS: A retrospective analysis was conducted on patients with a clinical diagnosis of benign lesions or OPMDs at the Oral Medicine and Pathology Unit (Maggiore Hospital, Trieste, Italy). Expert clinicians performed the clinical assessment, followed by biopsy and histopathological analysis. Diagnostic accuracy was evaluated through sensitivity, specificity, positive predictive value, and negative predictive value. Cohen's kappa (κ) coefficient was used to determine concordance between clinical and histological diagnoses. RESULTS: The histopathological analysis diagnosed the presence of benign lesions in 74.7% of cases and OPMDs in 25.3%. Sensitivity was highest for odontogenic cysts and tumors (92.06%) and lowest for ulcerative lesions/TUGSE (37.50%). Specificity exceeded 95% across most considered categories. The overall concordance between clinical and histological diagnoses was substantial (κ = 0.70). CONCLUSION: The misdiagnosis of OPMDs or benign lesions leads to diagnostic delays which seriously impact on the patient's therapeutic process. This survey highlights both high diagnostic accuracy and strong concordance between clinical and histological diagnoses. Integrating advanced diagnostic tools and constant clinicians' training is essential to minimize misdiagnoses.
BACKGROUND: Oropharyngeal dysphagia is a common issue among community-dwelling older adults and is associated with adverse health outcomes. This study examined whether the number of remaining teeth mediates the associati...BACKGROUND: Oropharyngeal dysphagia is a common issue among community-dwelling older adults and is associated with adverse health outcomes. This study examined whether the number of remaining teeth mediates the association between age and oropharyngeal dysphagia (OD) risk. METHODS: This cross-sectional study included 413 community-dwelling older adults (≥ 60 years) recruited from community health centers in Sulawesi, Indonesia. OD risk was assessed using a validated screening questionnaire. Oral examinations were conducted by trained nurses. Mediation analysis estimated the indirect, direct, and total effects of age on OD risk, adjusting for sex, educational level, hypertension, and diabetes mellitus. RESULTS: Participants' mean age was 69.9 years, with 15.3 remaining teeth. Mediation analysis revealed a significant indirect association between age and OD risk, mediated through the number of remaining teeth (adjusted β = 0.076, 95% CI: 0.034-0.114, p < 0.001). In contrast, the direct effect of age was not statistically significant. The total effect of age on OD risk remained significant. CONCLUSION: The number of remaining teeth statistically mediated the association between age and OD risk. Although causal inference is limited by the cross-sectional design, these findings highlight oral health as a potentially modifiable factor for reducing OD risk among older adults.
OBJECTIVE: Oral cancer, with a rising global incidence and poor prognosis, is associated with areca nut use in South and Southeast Asia. In this study, we addressed the effects of areca nut extract (ANE) on oral carcinog...OBJECTIVE: Oral cancer, with a rising global incidence and poor prognosis, is associated with areca nut use in South and Southeast Asia. In this study, we addressed the effects of areca nut extract (ANE) on oral carcinogenesis by modulating fibroblast behavior in oral tissue. METHODS: Cell viability, migration, invasion, and flow cytometry assays were applied to study cell behaviors. Cytokine array, enzyme-linked immunosorbent assay, phospho-kinase array, Western blot analysis, and oxygen consumption and glycolysis assays were performed to evaluate cell functions. Immunohistochemical and immunofluorescent staining using human and hamster oral tissues was applied to validate in vitro findings. RESULTS: Increased alpha smooth muscle actin (α-SMA) and fibroblast activation protein (FAP) were observed in fibroblasts from oral precancerous and cancer lesions. ANE increased mitochondrial metabolism in fibroblasts and induced myofibroblast transition. It enhanced epithelial-to-mesenchymal transition and granulocyte-macrophage colony-stimulating factor (GM-CSF) secretion in fibroblasts. Conditioned medium from ANE-treated fibroblasts and recombinant GM-CSF increased epidermal growth factor receptor (EGFR) phosphorylation and malignant transformation in dysplastic oral keratinocytes. In hamsters, ANE treatment increased GM-CSF expression in fibroblasts and EGFR phosphorylation in epithelial cells. CONCLUSION: ANE promotes epithelial-to-mesenchymal transition and GM-CSF secretion in fibroblasts, which activate EGFR signaling and malignant transformation of oral precancerous cells.
Brailo V, Lopez-Pintor RM, Harte M
… +21 more, Rogulj AA, Juras DV, Škrinjar I, Freitas MD, Posse JL, Monteiro L, Silva LM, Fricain JC, Naveau A, Lodi G, Lombardi N, Varoni E, López JL, Moreno SE, Ariyaratnam R, Alqarni AA, Ríordáin RN, Addison O, Li Y, Tamimi F, Albuquerque R
BACKGROUND: Artificial intelligence (AI) has emerged as a promising tool in dentistry, particularly in the early detection of oral cancer (OC) and oral potentially malignant disorders (OPMDs). Data focused on European de...BACKGROUND: Artificial intelligence (AI) has emerged as a promising tool in dentistry, particularly in the early detection of oral cancer (OC) and oral potentially malignant disorders (OPMDs). Data focused on European dental students and their knowledge/attitudes towards the use of AI for diagnosing OC/OPMDs are limited. METHODS: A cross-sectional online survey was conducted among final-year dental students from six European countries. The questionnaire assessed knowledge, attitudes, and perceived barriers regarding AI in the diagnosis of OC and OPMDs. Data were analysed using descriptive and comparative statistics to evaluate differences between countries. RESULTS: A total of 328 students participated (75% female, 25% male). Most students stated that they had not received formal training in AI (61%) and emphasised the need to incorporate such training into the dental curriculum (47%). Students from Portugal had highest overall knowledge scores, but at the same time, lowest overall attitude scores. The most commonly perceived barrier was insufficient training (87.8%). CONCLUSION: Final-year dental students demonstrate positive attitudes towards AI aiding in diagnosis of OC and OPMDs, although significant knowledge and skill gaps remain. Integrating structured AI education into dental curricula is essential to prepare future academics and clinicians for responsible and effective AI use.
OBJECTIVE: This study evaluated the efficacy and safety of hypericin-mediated photodynamic therapy (PDT) for oral Candida albicans (C. albicans) infections and explores how C. albicans reduction mediates clinical improve...OBJECTIVE: This study evaluated the efficacy and safety of hypericin-mediated photodynamic therapy (PDT) for oral Candida albicans (C. albicans) infections and explores how C. albicans reduction mediates clinical improvement. METHODS: A total of 107 patients (March 2023-March 2025) were assigned to a control group (n = 51, conventional antifungal therapy) or a study group (n = 57, hypericin + PDT). Post-treatment assessments included oral microbiota structure, α-diversity (Chao1, Shannon, Simpson), community differences (via PCoA and hierarchical clustering), and a mediation model to test C. albicans' role in lesion improvement. RESULTS: Chao1 (species richness) showed no significant difference, but the study group had lower Shannon/Simpson (microbial diversity). Opportunistic pathogens (e.g., C. albicans, Fusobacterium) decreased, while beneficial bacteria (e.g., Lactobacillus) increased. PCoA/clustering confirmed distinct community structures. C. albicans reduction mediated 53.1% of lesion size reduction (indirect effect = -2.656; 95% CI: 0.178-5.755). CONCLUSION: Hypericin + PDT effectively treats oral C. albicans infections safely. C. albicans is the core mediator for lesion area reduction, providing a basis for targeted clinical therapy.
BACKGROUND: The present study intends to evaluate the potential role of direct immunofluorescence (DIF) in the differential diagnosis of oral lichen planus (OLP) and oral lichenoid lesion (OLL) by means of meta-analysis....BACKGROUND: The present study intends to evaluate the potential role of direct immunofluorescence (DIF) in the differential diagnosis of oral lichen planus (OLP) and oral lichenoid lesion (OLL) by means of meta-analysis. METHODS: An exhaustive literature search across international databases (PubMed, Scopus, Embase, Cochrane Library and Web of Science) was performed up to October 2025. Quality evaluation was conducted on the retrieved studies, literature management was performed using EndNote 21.3 (Clarivate Analytics, Philadelphia, PA, USA) and meta-analyses were executed using RevMan 5.4 (The Cochrane Collaboration, London, UK) and Stata 18.0 (StataCorp LLC, College Station, TX, USA). RESULTS: Five studies were included in total, encompassing 465 participants. This meta-analysis of DIF positivity rates in tissues demonstrated significant differences with the following three antibodies between OLP and OLL: fibrin (Fib), IgA, IgM. The area under the curve (AUC) values of Fib and IgA indicated moderate diagnostic efficacy. CONCLUSIONS: Pooled analysis of five studies revealed that Fib, IgA, and IgM exhibited significantly higher positive rates in OLP than in OLL, indicating their promising potential for aiding the differential diagnosis of OLP. However, sole reliance on the positivity of a single antibody is insufficient for distinguishing OLP from OLL. Further research on the immunofluorescence patterns of these antibodies will help clarify the diagnostic criteria. TRIAL REGISTRATION: This report was preregistered on PROSPERO with the registration ID CRD420251088424; the registration form is provided in Appendix 1.
OBJECTIVE: To map the literature on management of surgical margins for oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL). METHODS: Searches were performed in five electronic databases and gray literatur...OBJECTIVE: To map the literature on management of surgical margins for oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL). METHODS: Searches were performed in five electronic databases and gray literature. Studies involving patients undergoing any type of surgical excision of OL or PVL were included. Data extraction focused on surgical technique, margin size, method of margin delineation, and recurrence outcome. Margin size was categorized in centimeters. RESULTS: Ninety-one studies were included. More than half of the studies (54.9%) did not report the width of surgical margins. Among those that did, margins between > 2 and < 3 mm were the most frequently reported (19.7%). Notably, 94.5% of the studies did not specify the criteria used to determine the margin width. Furthermore, 76.9% failed to describe the method used to delineate lesion margins. High recurrence was observed in 15.1% of OL cases with surgical margins ≤ 2 mm and in 40% of PVL cases with margins > 2 to ≤ 3 mm. Lesions with margins between 3 and 5 mm showed a lower recurrence rate. CONCLUSION: We identified a lack of standardization in the reporting of surgical margins. Excision with 5 mm of clinically healthy tissue should be considered the optimal approach for the surgical management.
INTRODUCTION: Hypoparathyroidism, an endocrine disorder causing hypocalcemia from inadequate PTH secretion, affects multiple systems and may correlate with salivary dysfunction and poor oral health. This study aimed to i...INTRODUCTION: Hypoparathyroidism, an endocrine disorder causing hypocalcemia from inadequate PTH secretion, affects multiple systems and may correlate with salivary dysfunction and poor oral health. This study aimed to investigate the effects of hypoparathyroidism on salivary calcium levels, flow rate, and parotid gland structure, exploring the implications for oral health of this patient population. MATERIALS AND METHODS: Conducted as a case-control study between January and June 2024, our research included 86 participants: 43 with hypoparathyroidism and 43 in a healthy control group. We compared participants' salivary calcium, phosphorus, and magnesium levels alongside salivary gland ultrasonography features, sialometry results, and oral health questionnaire outcomes. RESULTS: Salivary calcium levels were significantly lower in the hypoPT group [5.43 (4.13-9.65) mg/dL] compared to the control group [7.06 (4.02-13.18) mg/dL] (p < 0.001). No significant differences were observed in salivary phosphorus (p = 0.112) or magnesium (p = 0.938) levels. Despite similar parotid volumes, ultrasonography detected significantly higher prevalence of parenchymal heterogeneity in the hypoparathyroidism cohort (p = 0.025). Scores from the Multidisciplinary Salivary Gland Society questionnaire were significantly higher in the hypoparathyroidism group (p < 0.05), while sialometry measurements were significantly lower (p < 0.05). CONCLUSION: These results collectively suggested that hypoPT is a clinical condition with demonstrable effects on both oral health and salivary gland functions.
BACKGROUND: Oral lichen planus (OLP) is a chronic immune-mediated inflammatory disease with malignant potential, and its local inflammatory microenvironment is closely related to mucosal-associated invariant T cells (MAI...BACKGROUND: Oral lichen planus (OLP) is a chronic immune-mediated inflammatory disease with malignant potential, and its local inflammatory microenvironment is closely related to mucosal-associated invariant T cells (MAIT). Our prior work established OLP-associated fibroblasts (OLP/AFs) in creating the inflammatory milieu, but their interaction with MAIT cells remains unexplored. This study aims to investigate how OLP/AFs interact with MAIT cells. MATERIALS AND METHODS: Oral mucosal samples from OLP patients and healthy controls were selected for flow cytometry to detect MAIT cells. MR1 expression on fibroblasts was quantified via RT-qPCR, Western blot, immunohistochemistry, and immunofluorescence. For functional assays, OLP/AFs were stimulated with formaldehyde-fixed Escherichia coli (E. coli) to induce MR1 surface expression, then co-cultured with PBMCs±anti-MR1 blocking antibody and evaluated the activation status of MAIT. RESULTS: MR1 expression and MR1 fibroblast density were significantly elevated in OLP lesions compared to healthy controls. OLP/AFs demonstrated higher baseline MR1 expression than normal fibroblasts, which was further enhanced following E. coli stimulation. Co-culture of E. coli-stimulated OLP/AFs with peripheral blood mononuclear cells induced marked activation of MAIT cells. This was evidenced by significantly increased frequencies of CD69 MAIT cells and elevated secretion of pro-inflammatory cytokines and cytotoxic molecules. CONCLUSION: OLP/AFs activate MAIT cells via an MR1-dependent mechanism.
OBJECTIVE: To summarize current understanding of the roles of AMP-activated protein kinase (AMPK) in maintaining salivary gland (SG) homeostasis and its therapeutic potential in SG disorders characterized by acinar atrop...OBJECTIVE: To summarize current understanding of the roles of AMP-activated protein kinase (AMPK) in maintaining salivary gland (SG) homeostasis and its therapeutic potential in SG disorders characterized by acinar atrophy and fibrosis. METHODS: Recent studies and reviews on AMPK signaling, salivary gland pathology, and tissue regeneration were collected from PubMed, Medline, and Scopus databases. The evidence was synthesized to elucidate the regulatory functions of AMPK in SG injury and recovery. RESULTS: SG homeostasis relies on a balance between cell death and renewal, which is disrupted by severe damage. AMPK functions as a pivotal regulator in this process, promoting acinar cell survival, activating resident stem cells, inhibiting fibrosis, and modulating immune responses. AMPK activation attenuates inflammation and fibrogenesis, enhances tissue regeneration, and fosters a reparative immune microenvironment conducive to glandular recovery. CONCLUSION: AMPK serves as a central hub linking metabolic regulation, immune modulation, and tissue repair in SG disorders. Understanding its molecular mechanisms and optimizing AMPK activation strategies may provide novel therapeutic approaches to restore both function and structure in damaged salivary glands.