Search Results (111)

Oral leukoplakia (OL) is the most common potentially malignant oral disorder, with variable risk of progression to oral squamous cell carcinoma (OSCC). This study evaluated the chemopreventive and immunomodulatory potential of Artemisinin (ART) and Rubus occidentalis (RO), alone or combined (ARO), in a 4NQO-induced murine model. Mice received 4NQO (100 µg/mL) in drinking water, and treatments began at week 8. Animals were euthanized at weeks 12 and 16 for histological, apoptotic (caspases-3, -8, -9; calreticulin), inflammatory (IL-1β, IL-10, HMGB1), and immune (CD8, CD68, CD56, IFN-γ, GM-CSF) marker analyses. RO-treated animals showed delayed malignant transformation, with no carcinomas at week 16 and increased expression of caspase-9, calreticulin, HMGB1, IFN-γ, and GM-CSF, indicating transient activation of antitumor immune responses. ART-treated mice showed increased CD68 and reduced CD56 expression, suggesting an immunosuppressive profile and higher carcinoma incidence. The ARO combination did not improve outcomes beyond ART alone. These findings support the immunomodulatory and pro-apoptotic effects of RO in delaying OL progression, highlighting its chemopreventive potential. ART showed limited benefit under current conditions, warranting further investigation into dose optimization and synergistic strategies. Full article

Secukinumab (SEC) is a recombinant, fully human monoclonal antibody that is selective for interleukin-17A (IL-17A). SEC may increase the risk of developing infections such as oral herpes and oral candidiasis. The aim of this case report and literature review was to describe chronic hyperplastic candidiasis (CHC) in a patient with psoriasis (PsO) and psoriatic arthritis (PsA) treated with SEC. CHC is a rare and atypical clinical entity. A definitive diagnosis requires biopsy of the oral mucosa for histopathological diagnosis (PHD). The differential diagnosis includes hairy tongue, hairy leukoplakia, oral lichen planus (OLP), oral lichenoid reaction (OLR), leukoplakia, frictional keratosis, morsication, oral psoriasis, syphilis, and oral lesions associated with coronavirus disease (COVID-19). In addition to the usual factors (xerostomia, smoking, antibiotics, vitamin deficiency, immunosuppression, comorbidities), the new biological therapies/immunotherapies are a predisposing factor for oral candidiasis. The therapeutic approach must be multidisciplinary and in consultation with a clinical immunologist. Dentists and specialists (oral medicine, dermatologists, rheumatologists) must be familiar with the oral adverse events of the new biological therapies. Simultaneous monitoring of patients by clinical immunology and oral medicine specialists is crucial for timely diagnosis and therapeutic intervention to avoid possible adverse events and improve quality of life (QoL). Full article

Background: Oral leukoplakia (OL) and proliferative verrucous leukoplakia (PVL) remain challenging entities due to the absence of reliable prognostic biomarkers. All-trans retinoic acid (atRA), a pivotal modulator of epithelial differentiation and mucosal integrity, has been proposed as a candidate biomarker. This study sought to quantify plasma RA levels in patients with OL and PVL compared to healthy controls, assessing their potential clinical utility. Methods: A cohort of 40 participants was recruited, comprising 10 patients with OL, 10 with PVL, and 20 healthy controls. This nested case–control study was derived from previously characterized institutional databases of oral potentially malignant disorders. Plasma samples were analyzed for atRA concentration using high-precision mass spectrometry. Statistical comparisons were conducted to evaluate differences between groups and associations with clinical outcomes. Results: Patients with homogeneous OL exhibited significantly reduced plasma atRA concentrations (mean 2.17 ± 0.39 pg/mL) relative to both PVL patients (2.64 ± 0.56 pg/mL) and healthy controls (2.66 ± 0.92 pg/mL), with p-values of 0.009 and 0.039, respectively. No statistically significant difference was found between PVL patients and controls. Furthermore, atRA levels demonstrated no correlation with clinicopathological variables or malignant progression within the PVL cohort. Conclusions: These preliminary findings indicate that diminished plasma atRA levels may serve as a prognostic marker for homogeneous oral leukoplakia, whilst its role in PVL appears limited. However, effect estimates were imprecise, and additional studies are warranted. Full article

Background/Objectives: Oral leukoplakia (OL) is a prevalent oral potentially malignant disorder. Despite its clinical relevance, the molecular basis of its progression to malignancy is not yet fully elucidated. This scoping review of systematic reviews and meta-analyses aimed to synthesize current knowledge and evidence gaps regarding the implications of hallmarks of cancer expression in OL malignant transformation. Methods: A systematic search was conducted in MEDLINE, Embase, DARE, and the Cochrane Library to identify systematic reviews (with or without meta-analysis) published up to April-2025. Results: Twenty-two systematic reviews were included. The most frequently explored hallmark was activation of invasion and metastasis (n = 12; 32.40%), followed by tumor-promoting inflammation (n = 10; 27.03%), evasion of growth suppressors (n = 8; 21.60%), sustained proliferative signaling (n = 3; 8.10%), energy metabolism reprogramming (n = 2; 5.40%), replicative immortality (n = 1; 2.70%), and resistance to cell death (n = 1; 2.70%). No evidence was found for angiogenesis or immune evasion in OL. Conclusions: Available evidence indicates that OL may develop oncogenic mechanisms in early stages of oral oncogenesis, especially those related to sustained proliferation, evasion of growth suppressor signals, and cellular migration and invasion. Chronic inflammation also may facilitate the acquisition of other hallmarks throughout the multistep process of oral carcinogenesis. These findings also reveal evidence gaps in underexplored hallmarks of cancer, which highlights the need to expand future primary- and secondary-level investigations to better define the molecular mechanisms underlying OL malignant transformation. Full article

This study presents the findings of an academic extension project focused on promoting oral health and diagnosing oral lesions in institutionalized elderly individuals. The project involved visits by students and faculty to two nursing homes in southern Brazil. Data collection included extraoral and intraoral clinical examinations and educational activities such as lectures and the distribution of printed materials on oral and denture hygiene. According to caregiving staff, oral hygiene, including denture cleaning, was generally performed once daily during morning showers. A total of 118 older adults (68 males and 50 females; mean age 76.1 ± 8.6 years) were examined. Forty-nine used dentures, of whom only 24 (49%) reported satisfaction with their prostheses. In total, 42 oral lesions were identified, mainly angular cheilitis (8), inflammatory fibrous hyperplasia (7), irritation fibroma (7), frictional hyperkeratosis (7), prosthetic stomatitis (5), actinic cheilitis (3), traumatic ulcers (3), and leukoplakia (2). Educational sessions also targeted caregivers, offering practical guidance for improving hygiene practices. The results underscore the need for better oral care and improved access to dental services for institutionalized elderly populations. Academic extension activities play a valuable role in health promotion and in training future professionals in elderly care. Full article

Leukoplakia is a condition marked by white patches on the inner surfaces of the oral cavity. Its potential to progress to oral squamous cell carcinoma underscores the need for effective screening and early diagnosis procedures. We employed NMR-based salivary and tissue metabolomics to identify potential biomarkers for leukoplakia and dysplastic leukoplakia. Univariate and multivariate methods were used to evaluate the NMR-derived metabolite concentrations. The salivary metabolite profile of leukoplakia exhibited specific alterations compared to healthy controls. These metabolic changes were more pronounced in cases of dysplastic lesions. Multivariate ROC curve analysis, based on a selection of salivary metabolites, ascribed high diagnostic accuracy to the models that discriminate between dysplastic and healthy cases. However, NMR analysis of tissue biopsies was ineffective in extracting metabolic signatures to differentiate between lesional, peri-lesional, and healthy tissues. Our pilot study employing a metabolomics-based approach led to the development of salivary models that represent a complementary strategy for clinically detecting leukoplakia. However, larger-scale validation is required to fully evaluate their diagnostic potential and to effectively stratify leukoplakia patients according to dysplasia status. Full article

Background and Objectives: Oral cancer remains a critical global health burden. Oral potentially malignant disorders (OMPDs) such as leukoplakia and oral lichen planus can precede oral squamous cell carcinoma (OSCC). Inflammation, tissue remodeling, and dysregulated signaling pathways are central to malignant transformation. This observational study aimed to evaluate the expression patterns of Maspin, β-catenin, and MMP-14 by immunohistochemistry (IHC) in oral leukoplakia, oral lichen planus, OSCC, and normal mucosa, exploring associations with lesion type, with no prognostic inferences drawn from a single timepoint. Materials and Methods: Biopsy specimens from 67 patients presenting with oral lesions (27 leukoplakia, 22 lichen planus, 18 OSCC), and 10 healthy controls were collected between January 2015 and January 2023. Inclusion criteria were age over 18 years and no other chronic illness, and a histopathologic diagnosis of oral leukoplakia, oral lichen planus or OSCC. Exclusion criteria were smokers, alcohol abuse, and prior head and neck radiotherapy, prior immunosuppressive therapy, systemic inflammatory diseases, absence of histopathological confirmation of the clinical diagnosis, and squamous cell carcinoma of the vermilion. Two pathologists independently scored staining in 10 high-power fields. Normal mucosa served as baseline. Immunohistochemical analysis was conducted using specific antibodies targeting Maspin, β-catenin, and MMP-14. Marker expression was assessed using a semi-quantitative scoring system based on staining intensity and classified into four categories: negative (−), weakly positive (+) for 1–10%, moderately positive (++) for 11–50%, and highly positive (+++) for more than 50%. Results: Maspin showed moderate (++) cytoplasmic/nuclear staining in leukoplakia and lichen planus in 78% of cases and high (+++) in OSCC and stroma in all cases. β-catenin shifted from membranous moderate positivity in 100% of OPMD cases to cytoplasmic/nuclear high positivity in all cases of OSCC. MMP-14 showed positivity (+) in 89% of OPMDs and high positivity (+++) in 100% of OSCC. Conclusions: Maspin, β-catenin, and MMP-14 exhibit distinct expression patterns across lesion types. While Maspin may reflect early tissue remodeling, β-catenin and MMP-14 changes suggest Wnt signaling activation and matrix remodeling in OSCC. Longitudinal studies are needed to establish their predictive value. This observational study refrains from prognostic claims and instead highlights biomarkers for future validation. Full article

Background: Previous attempts to treat oral potentially malignant disorders OPMDs) effectively have failed. Longitudinal studies investigating the effects of comorbid diseases improvement on OPMDs are not yet available. Therefore, the current study examined the effects of comorbid disease improvement on OPMDs healing, both in oral lichen planus (OLP) and oral leukoplakia (OL) patients. Methods: The data from 197 consecutive patients (144 females and 53 males, age ± SD: 55.19 ± 12.37 years, with ages ranging from 23 to 91 years), with oral lesions considered OLP and OL, were processed and evaluated. The frequency of comorbid diseases and the presence of HPV (here, subtypes were not evaluated) in the lesions in OLP and OL patient groups were evaluated and compared to the results of controls (n = 139). Risk models for OLP and OL lesions were established. High-risk models for erosive–atrophic OLP and non-homogeneous OLP were also described. The influence of comorbid disease improvement was also evaluated. Lesions were scored at the first and last visit (full recovery = 0, improvement = 1, and no improvement = 2). Results: One hundred and ninety-seven patients (144 OLP + 53 OL) were followed up for an average of 47.66 months (min–max: 1–203 months, SD: 54.19). Based on the established models, HPV infection, iron deficiency, diabetes, and thyroid function disorders seem to act as risk factors for OLP and may also affect OL formation. The improvement in comorbid diseases can cause significant improvement in OLP and OL lesions. Conclusions: By meticulous follow-up of comorbid diseases, improvement in OLP and OL lesions can be achieved. 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/Objectives: Proliferative verrucous leukoplakia (PVL) is an oral disorder with the greatest degree of malignant transformation. However, it is relatively rare. This study compared the clinical characteristics of patients with oral squamous cell carcinoma (OSCC) who had and had not been previously diagnosed with PVL. Methods: This case control study compared the clinical characteristics of patients classified as early (T1 and T2) or advanced (T3 and T4) OSCC according to the T size of the Tumor, Node, Metastasis (TNM) classification, including age, gender, location, and clinical type of oral squamous cell carcinoma. The analysis involved 140 patients. Group 1: 50 OSCC patients with PVL (OSCC-PVL) and Group 2: 90 OSCC patients without PVL (OSCC-noPVL). Results: The patients with OSCC-PVL were younger than those with OSCC-noPVL, but this did not reach statistical significance. Regarding patient gender, those with OSCC-PVL were much more frequently female (70%), while OSCC-noPVL was more prevalent in men (65.5%) (p < 0.01). There were also significant differences in the oral locations between the two groups: the gingiva was most prevalent in OSCC-PVL and the tongue in OSCC-noPVL. Erythroleukoplastic forms were significantly more common in OSCC-PVL (30% vs. 7.7%), while ulcerated forms were more frequent in OSCC-noPVL (63.3% vs. 42%). Finally, early T stages were much more prevalent in our patients with OSCC-PVL. Conclusions: We found that OSCC preceded by PVL was much more frequent in women, had less aggressive clinical forms, and had significantly more frequent early T stages than in OSCC-noPVL. Full article

Oral potentially malignant disorders (OPMDs) are conditions that carry an increased risk of malignant transformation, including oral leukoplakia and oral lichen planus. Current management approaches differ based on each condition’s unique etiology and pathophysiology, but all available treatment methods have notable limitations. This has prompted continued efforts to identify more effective therapeutic options. Photodynamic therapy (PDT) has emerged as a minimally invasive yet potent alternative for treating OPMDs. This systematic review examines the efficacy of PDT mediated by toluidine blue and chlorin-e6 (Photolon) in managing OPMDs. Following the PRISMA guidelines, eight relevant studies published between 2010 and 2024 were included. Data on the study design, protocols, light parameters, and photosensitizer characteristics were collected to evaluate treatment outcomes. The reviewed evidence suggests that toluidine-blue- and chlorin-e6-mediated PDT holds promise as a minimally invasive treatment modality for OPMDs, especially for oral lichen planus and oral leukoplakia. Studies indicate its potential as an alternative or adjunct therapy, particularly for symptomatic or refractory oral lichen planus. However, discrepancies in study designs and treatment protocols, coupled with the limited number of trials, impeded direct comparisons. Toluidine-blue- and chlorin-e6-mediated PDT shows significant potential as a therapeutic option for OPMDs. Nonetheless, further investigations—including large-scale randomized controlled trials, standardized treatment guidelines, and the exploration of additional OPMDs beyond oral lichen planus and oral leukoplakia—are necessary in order to fully establish its clinical utility and facilitate widespread adoption. Full article

Understanding the early molecular events driving oral carcinogenesis is vital for diagnosing oral squamous cell carcinoma (OSCC) promptly. While metabolic differences between oral leukoplakia (OLK), OSCC, and healthy oral mucosa have been reported, the metabolic changes distinguishing malignant transformed OLKs (MT-OLK) from non-transformed OLKs (NT-OLK) remain unexplored. Here, we examine the metabolomic profiles of 5 cases of MT-OLK and 15 of NT-OLK to identify key predictive molecules using untargeted high-performance liquid chromatography-mass spectrometry. The potentially discriminant compounds were highlighted through a robust statistical analysis workflow, and the dysregulated metabolic pathways were illustrated by enrichment analysis. Seventeen molecular features, primarily lipids—including phospholipids, oxidised lipids, cholesteryl esters, and fatty acids—were identified as discriminants between MT-OLK and NT-OLK across statistical and bioinformatic approaches. Pathway enrichment analysis revealed alterations in lipid metabolism, particularly fatty acid synthesis and degradation, steroid hormone biosynthesis, and glycerophospholipid metabolism. Predictive models showed high accuracy (AUC = 0.88) in distinguishing the two groups. This study suggests that metabolomics has the potential to differentiate between MT-OLK and NT-OLK by identifying candidate biomarkers that may contribute to the understanding of malignant transformation. Validation in larger cohorts is warranted to translate these findings into clinical practice. Full article

Background/Objectives: Oral leukoplakia (OLK) is an oral mucosal lesion classified in the oral potentially malignant disorder group and is associated with an increased risk of malignant transformation (MT). The aim of this study was to compare the clinical and histopathological features of two OLK groups, a group of smokers and a group of non-smokers. Methods: In this retrospective study, a cohort of 154 patients with OLK was divided into two groups based on the presence of smoking as a major risk factor. OLK diagnoses were established via clinical and histopathological examination. Results: Females were more abundant in the non-smoking group than in the smoking group, where males were more abundant (p < 0.001). The average age of the smokers was lower than that of the non-smokers (p = 0.003). In the smokers, the buccal mucosa was most frequently affected, while in the non-smokers, the gums and the tongue were primarily involved (p = 0.016). In female smokers, involvement of the buccal area and multiple-site involvement were statistically significantly more frequently observed compared to that in female non-smokers (p = 0.006). Non-dysplastic lesions were predominant in both groups, with severe dysplasia observed more frequently in the non-smokers than in the smokers. MT was higher in the non-smoker group compared to that in the smoker group. Conclusions: OLK in smokers is different from OLK in non-smokers concerning female gender involvement, site location, the number of lesions, and the MT rate. Full article

Background and Objectives: Oral cancer remains a critical global health concern, with oral squamous cell carcinoma (OSCC) being the most prevalent form. Oral potentially malignant disorders (OPMDs), such as oral leukoplakia (OLK), oral lichen planus (OLP), and actinic cheilitis (AC), often precede OSCC. Identifying reliable biomarkers is vital for assessing malignant transformation risk. The present study aimed to evaluate the immunohistochemical expression of differentiated embryonic chondrocyte 1 (DEC1), a marker of dysplasia severity, and cluster of differentiation 44 (CD44), which is associated with cancer progression, in OPMD and OSCC tissues. Materials and Methods: A retrospective analysis was conducted on 145 biopsy specimens from January 2015 to January 2023, comprising normal mucosa (NM), OLK, OLP, AC, and OSCC. DEC1 and CD44 expression levels were assessed using immunohistochemical staining. Positivity scores were determined based on staining intensity and extent, with statistical analyses performed using SPSS software (SPSS Inc., Chicago, IL, USA, version 29.0 for Windows). Results: It was found that CD44 expression significantly increased across OPMD and OSCC compared to NM (p < 0.001). Conversely, DEC1 expression was consistent across lesion types and dysplasia levels. CD44 expression was the highest in AC and OSCC, underscoring its potential role as a progression marker. Conclusions: The results indicate that CD44 is a more sensitive marker for assessing dysplastic severity and malignant transformation, while DEC1 may serve as a complementary marker for early-stage evaluation. Further research involving larger cohorts is needed to confirm these findings. Full article

Objective: The aim of this systematic review and meta-analysis was to qualitatively and quantitatively evaluate the current evidence on the significance of the loss of early stages of oral carcinogenesis in lesions diagnosed according to clinical and/or histopathological criteria and their evolution to oral cancer. Materials and Methods: We searched MEDLINE (through PubMed), Embase, Scopus and Web of Science for primary-level studies published before November 2024, designed as prospective or retrospective longitudinal cohorts, and not restricted by language or publication date. The risk of bias was critically assessed using the QUIPS tool. Meta-analyses, heterogeneity exploration, sensitivity and small-study effect analyses were conducted. Results: The inclusion criteria were met by six primary-level studies, which recruited 330 patients with OPMDs with follow-up data. The loss of pRb expression, assessed through immunohistochemistry, was significantly associated with a higher malignant transformation risk of OPMDs (RR = 1.92, 95%CI = 1.25–2.94, p = 0.003). The leukoplakia subgroup retained this significant association (p = 0.006), being the OPMD where the loss of pRb expression showed the best predictive value for malignant transformation (RR = 2.00, 95%CI = 1.22–3.29). Regarding the immunohistochemical technique and scoring methods, better performance and results were achieved by applying a cutoff point > 10% pRb-positive cells with nuclear staining (RR = 2.10, 95%CI = 1.30–3.38, 95%CI = 0.002). Conclussion: The present systematic review and meta-analysis supports that the loss of expression of the tumor suppressor pRb, assessed through immunohistochemistry, is a predictor of the malignant transformation risk of oral leukoplakias. Future studies are needed in other OPMDs following the recommendations provided based on current evidence gaps. Full article