Increased Plasmatic Levels of Exosomes Are Significantly Related to Relapse Rate in Patients with Oral Squamous Cell Carcinoma: A Cohort Study.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is characterized by an immunosuppressive tumor microenvironment. Their plasma-derived exosomes deliver immunomodulatory molecules and cargo that correlate significantly with clinical parameters. This study aims to assess the exosomal profile as a potential tool for early detection of relapse and long-term outcomes in OSCC patients undergoing conventional therapy. METHODS: 27 OSCC patients with a median 38-month follow-up were included in this study. The relationship between NTA-derived parameters and clinical pathological parameters was examined, and receiver operating characteristic (ROC) curves were utilized to evaluate the diagnostic efficacy of these values in detecting cancer relapse. RESULTS: Plasmatic levels of exosomes prior to surgery showed a drastic reduction after surgical intervention (8.08E vs. 1.41 × 109 particles/mL, p = 0.006). Postsurgical concentrations of exosomes were higher in patients who experienced relapse compared to those who remained disease-free (2.97 × 109 vs. 1.11 × 109 particles/mL, p = 0.046). Additionally, patients who relapsed exhibited larger exosome sizes after surgery (141.47 vs. 132.31 nm, p = 0.03). Patients with lower concentrations of exosomes prior to surgery demonstrated better disease-free survival compared to those with higher levels (p = 0.012). ROC analysis revealed an area under the curve of 0.82 for presurgical exosome concentration in identifying relapse. CONCLUSIONS: Presurgical exosomal plasmatic levels serve as independent predictors of early recurrence and survival in OSCC. All in all, our findings indicate that the detection of peripheral exosomes represents a novel tool for the clinical management of OSCC, with potential implications for prognosis assessment.

Understanding Solid-Based Platelet-Rich Fibrin Matrices in Oral and Maxillofacial Surgery: An Integrative Review of the Critical Protocol Factors and Their Influence on the Final Product.

Platelet-rich fibrin (PRF) is a second-generation platelet concentrate whose use in clinical practice has been widely disseminated. This has led to the development of several commercial protocols, creating great confusion as to the terminology and implications of each of them. This integrative review aims to identify the critical factors of each of the phases of the solid-based PRF matrix protocol and their possible influence on their macro- and microscopic characteristics. An electronic search of the MEDLINE database (via PubMed), Web of Science, Scopus, LILACS, and OpenGrey was carried out. The search was temporarily restricted from 2001 to 2022. After searching, 43 studies were included that met the established criteria. There were numerous factors to consider in the PRF protocol, such as the material of the blood collection tubes, the duration of phlebotomy, the parameters related to blood centrifugation, the time from centrifugation to dehydration of the fibrin clots and their dehydration into membranes, as well as the time to clinical use. These factors influenced the macro- and microscopic characteristics of the PRF and its physical properties, so knowledge of these factors allows for the production of optimised PRF by combining the protocols and materials.

Predictive value of CDKN2A/p16INK4a expression in the malignant transformation of oral potentially malignant disorders: Systematic review and meta-analysis.

BACKGROUND: Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16INK4a has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16INK4a immunohistochemical expression and the risk of malignization of OPMDs. MATERIAL AND METHODS: After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16INK4a expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran's Q test, Galbraith plot and Egger and Begg Mazumdar's rank tests. RESULTS: Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36-2.96 - I2 = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier. CONCLUSION: Pooled analysis showed that p16INK4a assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16INK4a overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDs.

Overexpression of E-Cadherin Is a Favorable Prognostic Biomarker in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Oral squamous cell carcinoma (OSCC) is characterized by poor survival, mostly due to local invasion, loco-regional recurrence, and metastasis. Given that the weakening of cell-to-cell adhesion is a feature associated with the migration and invasion of cancer cells, different studies have explored the prognostic utility of cell adhesion molecules such as E-cadherin (E-cad). This study aims to summarize current evidence in a meta-analysis, focusing on the prognostic role of E-cad in OSCC. To find studies meeting inclusion criteria, Scopus, Web of Science, EMBASE, Medline, and OpenGrey databases were systematically assessed and screened. The selection process led to 25 studies, which were considered eligible for inclusion in the meta-analysis, representing a sample of 2553 patients. E-cad overexpression was strongly associated with longer overall survival (OS) with Hazard Ratio (HR) = 0.41 95% confidence interval (95% CI) (0.32-0.54); p < 0.001 and disease-free survival with HR 0.47 95% CI (0.37-0.61); p < 0.001. In terms of OS, patients with tongue cancer experienced better survivability when expressing E-cad with HR 0.28 95% CI (0.19-0.43); p < 0.001. Globally, our findings indicate the prognostic role of the immunohistochemical assessment of E-cad in OSCC and its expression might acquire a different role based on the oral cavity subsites.

Regeneration of periodontal bone defects with mesenchymal stem cells in animal models. Systematic review and meta-analysis.

The aim of this study was to evaluate the efficacy of mesenchymal stem cells (MSCs) in the regeneration of periodontal bone defects in animal models. A systematic review and meta-analysis were conducted following the PRISMA guidelines, and the study was recorded in PROSPERO under reference number CDR42021247462. The PICO question was: is periodontal regeneration (cementum, periodontal ligament and alveolar bone) with MSCs more effective than other techniques? Three groups were considered: Group 1: MSCs alone or mixed with regenerative materials. Group 2: only regenerative materials. Group 3: no regenerative material nor MSCs. The search was conducted using MeSH with a total of 18 articles for qualitative analysis and 5 for quantitative analysis. For the meta-analysis, a modification of the effect size algorithm was developed, which considered a comparison of means between treatments using the Student's t sample distribution. When comparing the effect size between Group 1 and Group 2, the effect size for the new cementum was 2.83 mm with an estimated confidence interval of 95% (CI 95%) between 0.48 and 5.17 mm. When considering the fit to a random-effects model, the combined variance (τ2) was 6.1573 mm, with a standard deviation (SD) of 5.6008 mm and a percentage of total heterogeneity I2 of 92.33% (p < 0.0001). For new bone, the effect size was 0.88 mm, CI 95% - 0.25 to 2.01 mm, τ2 = 1.3108 mm (SD = 1.2021 mm) and I2 = 80.46%, p = 0.0004). With regard to the new periodontal ligament, it was not possible for the meta-analysis to be performed. MSCs have a greater capacity for tissue regeneration in root cementum than in alveolar bone compared to other regenerative materials.

Drug use, risk perceptions and attitudes towards drug use amongst medical and dentistry students.

AIMS: To analyse the use of psychoactive substances and the risk perceptions amongst odontology and medical students. To study their perceptions, attitudes and knowledge, and to evaluate their motivation when helping their patients to stop using these substances. METHODS: A cross-sectional study was conducted amongst 962 students in Spain, using validated questionnaires on an anonymous basis. RESULTS: Amongst these students, drug use varies and increases with age as assessed by the DAST and CAST tests, with more problematic use being observed as the academic cycle progresses (p < .001). Participants in the 2nd cycle presented higher consumption than those in the 1st cycle, in the univariate model (OR = 1.77, IC 95% 1.27-2.48, p = .001) and in the adjusted model (OR = 1.86, IC 95% 1.32-2.62, p < .001). Regarding CAST, non-problematic use in the 1st cycle versus the 3rd cycle presented an OR = 8.69 (IC 95% 4.50-16.78, p < .001) and for low risk use it presented an OR = 15.18 (IC 95% 1.83-14.68). Only 46.7% considered using marijuana on a regular basis as a high risk, whilst 60.5% stated that smoking a pack of cigarettes represents a high risk. Alcohol was the substance for which the risk perception was lowest. 66.2% are in the maintenance stage "I provide my regular drug-using patients help to give up," with women being more likely to be in this stage (p = .012). CONCLUSIONS: High risk of drug use increases after the 1st cycle in Dentistry and in Medicine. Training programmes should be implemented in both degrees, focusing on the 1st years in order to simultaneously prevent drug use amongst students.

Oral Chronic Hyperplastic Candidiasis and Its Potential Risk of Malignant Transformation: A Systematic Review and Prevalence Meta-Analysis.

Chronic hyperplastic candidiasis (CHC) is a prototypical oral lesion caused by chronic Candida infection. A major controversy surrounding CHC is whether this oral lesion owns malignant transformation (MT) potential. The aim of the present study was to evaluate current evidence on the MT of CHC and to determine the variables which have the greatest influence on cancer development. Bibliographical searches included PubMed, Embase, Web of Science, Scopus and LILACS. The cohort studies and case series used to investigate the MT of CHC were deemed suitable for inclusion. The quality of the enrolled studies was measured by the Joanna Briggs Institute scale. Moreover, we undertook subgroup analyses, assessed small study effects, and conducted sensitivity analyses. From 338 studies, nine were finally included for qualitative/quantitative analysis. The overall MT rate for CHC across all studies was 12.1% (95% confidential interval, 4.1-19.8%). Subgroup analysis showed that the MT rate increased when pooled analysis was restricted to poor quality studies. It remains complex to affirm whether CHC is an individual and oral, potentially malignant disorder according to the retrieved evidence. Prospective cohort studies to define the natural history of CHC and a consensus statement to clarify a proper set of diagnostic criteria are strongly needed. PROSPERO ID: CRD42022319572.

DNA Methylation by Bisulfite Next-Generation Sequencing for MLH1 and MGMT in Oral Squamous Cell Carcinomas and Potentially Malignant Disorders: An Integrative Analysis towards Field Cancerization.

Background and Objectives: MGMT methylation is a well-described biomarker in several solid tumors and MLH1 seems to occur in the initial stages of oral carcinogenesis. The aims of this study were to evaluate MHL1 and MGMT methylation levels in oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMDs), and to integrate this information with The Cancer Genome Atlas (TCGA) database. Materials and Methods: To determine the percentage of gene methylation in MLH1 and MGMT, pyrosequencing analysis was conducted. Samples were divided as follows: (1) patients diagnosed with OSCC (N = 16); (2) patients with OPDM who developed OSCC in the same location (N = 47); and (3) patients with OPDM who developed OSCC in a different location (N = 22). As a validation cohort in this study, data from The Cancer Genomic Atlas (TCGA) database, particularly regarding Head and Neck Squamous Cell Carcinoma, was used. Results: Overall MLH1 methylation levels of 8.6 ± 11.5% and 8.1 ± 9.2% for MGMT were obtained. With regard to MHL1, the OSCC presented the highest degree of methylation with 9.3 ± 7.3% (95%CI 5.1-13.6), and with regards to MGMT, the simultaneous malignancy group presented the highest degree of methylation with 10 ± 13.5% (95%CI 6-10), although no significant differences were found between the groups (p = 0.934 and p = 0.515, respectively). The estimated survival was higher for MGMT methylated cases (19.1 months, 95%CI 19.1-19.1) than for unmethylated cases (9.4 months, 95%CI 6-12.8), but not statistically significant. Conclusions: Our results did not show a correlation between MGMT and MLH1 methylation and any clinicopathological feature or survival in our institutional cohort. MLH1 methylation was present mainly in OSCC, whilst MGMT in OPMD represented a modest contribution to field cancerization, with an overall consistency with the TCGA database.

Critical update, systematic review, and meta-analysis of oral erythroplakia as an oral potentially malignant disorder.

BACKGROUND: Oral erythroplakia has been classically considered as the potentially malignant disorder with the highest rate of malignant development into squamous cell carcinoma. This critical systematic review and meta-analysis aim to estimate the malignant development rate of oral erythroplakia and identify the associated risk factors. METHODS: We performed a bibliographic search in PubMed, Scopus, Web of Science, Embase, and LILACS, with keywords "erythroplakia," "erythroplasia," "malignant transformation," "malignant development," "malignization," "carcinogenesis," "oral cancer," "oral squamous cell carcinoma," "mouth neoplasm," and "prognosis." Meta-analysis was conducted using a random-effects model. RESULTS: Ten observational studies with 441 patients met the inclusion criteria, whose mean malignant development rate was 12.7% and with a mean follow-up period of patients of 6.66 years. In the initial biopsy, 42.8% of oral erythroplakia were already squamous cell carcinoma. The buccal mucosa was the most frequent location of oral erythroplakia, but the floor of the mouth was the most common site of malignant development. All patients who underwent malignant development showed epithelial dysplasia on the initial diagnostic biopsy. CONCLUSION: Overall malignant development rate of OE in the meta-analysis was 19.9%. We could not associate any specific clinicopathological feature with the malignant development. The presence of epithelial dysplasia in the initial biopsy remains the worst prognostic factor. Further observational studies on OE are needed, with well-established diagnostic criteria and good clinical follow-up, in order to identify the true risk of malignant development of oral erythroplakia and the related risk factors.