Comparative clinicopathological study of the main anatomic locations of oral squamous cell carcinoma.

OBJECTIVE: To analyze the clinicopathological and evolutionary profile of the main locations of oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This is a retrospective study on 133 patients treated for OSCC. The group was composed of 48 women and 85 men, with a mean age 63.9 ± 12.73 years. Most cases involved the lingual border of tongue (63), followed by the gingiva (36) and the floor of mouth (34). A comparative analysis was performed using multinomial regression. RESULTS: There were significant differences regarding age, sex, tobacco and alcohol consumption, liver pathology, oral potentially malignant disorders, and bone and perineural invasion. In multivariate regression, tobacco consumption, and bone invasion remained significant. There were no significant differences in relation to prognosis. CONCLUSION: The location of OSCC is an important factor in the clinicopathological assessment of this neoplasm. The main locations of OSCC show differential etiopathogenic and clinicopathological aspects. Tobacco consumption has a great relevance in the floor of mouth; nonetheless, it is less important in the tongue border and the gum, which suggests other pathogenic factors. It is necessary to consider the anatomical location of OSCC in preventive protocols, with the aim of reducing its high mortality.

Epidemiological, clinical, and prognostic analysis of oral squamous cell carcinoma diagnosed and treated in a single hospital in Galicia (Spain): a retrospective study with 5-year follow-up / Análisis epidemiológico, clínico y pronóstico del carcinoma oral de células escamosas diagnosticado y tratado en un único hospital de Galicia (España): un estudio retrospectivo con un seguimiento de 5 años

Background: Oral cancer is a common neoplasm worldwide, mostly corresponding to squamous cell carcinoma(OSCC). Unfortunately, its overall prognosis remains poor, with no improvement in recent decades. In this study,we have analysed the epidemiological, clinical, and prognostic characteristics of OSCC on patients of a specificSpanish region (Galicia), in order to improve its prognosis and apply effective preventive and early diagnosismeasures.Material and Methods: We retrospectively analysed 243 cases of OSCC, diagnosed and treated in a single hospitalcentre in Galicia between 2010 and 2015 (minimum of 5 years of evolution). Overall and specific survival werecalculated (Kaplan-Meier) and associated variables were identified (log rank test and Cox regression).Results: The mean age of the patients was 67 years, with the majority being male (69.5%), smokers (45.9%) andalcohol consumers (58.6%), who lived in non-urban areas (79.4%). Cases diagnosed at advanced stages entailedthe 48.1% of the sample, and 38.7% of cases relapsed. The 5-year overall and disease-specific survival rates were39.9% and 46.1%, respectively. Patients who consumed tobacco and alcohol had a worse prognosis. OSCC casesreferred to hospital by specialist dentists had a better prognosis, as those who were previously diagnosed with anoral potentially malignant oral disorder (OPMD) or received dental care during OSCC treatmen. Conclusions: In view of these findings, we conclude that OSCC in Galicia (Spain) still has a very poor overall prog-nosis, which is mainly related to the advanced age of the patients and the late diagnosis. Our study highlights thebetter survival of OSCC in relation to the referring health professional, the presence of a previous OPMD and thedental care after diagnosis. This demonstrates the importance of dentistry as a health profession involved in the earlydiagnosis and multidisciplinary management of this malignant neoplasm.(AU)

Tumor budding is a prognostic factor in head and neck squamous cell carcinoma: A comprehensive meta-analysis and trial sequential analysis.

BACKGROUND: Mortality is linked to tumor budding (TB) in certain neoplasms. TB as a relevant histopathological feature is conditioned by tumor site, a specific study on head and neck squamous cell carcinoma (HNSCC) is needed. METHODS: A comprehensive meta-analysis was undertaken to investigate the relationship between TB and HNSCC-related outcomes. RESULTS: Overall 42 studies were included. Patients harboring high TB reported an Overall Survival (OS) Hazard Ratio (HR) of 2.63 (95% confidential interval (CI) 2.04-3.39; p-value < 0.001), Disease-free Survival (DFS) HR of 1.88 (95%CI 1.57-2.24; p-value <0.001) and Disease-specific Survival (DSS) HR of 2.14 (95%CI 1.81-2.52; p-value <0.001). Lymph Node Metastasis (LNM) studies harbored null heterogeneity and marked association with TB (Odds Ratio (OR) = 4.48, 95%CI 2.97-6.76; p-value < 0.001). Trial Sequential Analysis (TSA) supported definitive results for DSS. CONCLUSION: The study has provided compelling evidence that there is a significant association between TB and a worse prognosis for HNSCC.

Identification of Proteomic Biomarkers in Proliferative Verrucous Leukoplakia through Liquid Chromatography With Tandem Mass Spectrometry.

Proliferative verrucous leukoplakia (PVL) is an oral potentially malignant disorder associated with high risk of malignant transformation. Currently, there is no treatment available, and restrictive follow-up of patients is crucial for a better prognosis. Oral leukoplakia (OL) shares some clinical and microscopic features with PVL but exhibits different clinical manifestations and a lower rate of malignant transformation. This study aimed to investigate the proteomic profile of PVL in tissue and saliva samples to identify potential diagnostic biomarkers with therapeutic implications. Tissue and saliva samples obtained from patients with PVL were compared with those from patients with oral OL and controls. Label-free liquid chromatography with tandem mass spectrometry was employed, followed by qualitative and quantitative analyses, to identify differentially expressed proteins. Potential biomarkers were identified and further validated using immunohistochemistry. Staining intensity scan analyses were performed on tissue samples from patients with PVL, patients with OL, and controls from Brazil, Spain, and Finland. The study revealed differences in the immune system, cell cycle, DNA regulation, apoptosis pathways, and the whole proteome of PVL samples. In addition, liquid chromatography with tandem mass spectrometry analyses showed that calreticulin (CALR), receptor of activated protein C kinase 1 (RACK1), and 14-3-3 Tau-protein (YWHAQ) were highly expressed in PVL samples. Immunohistochemistry validation confirmed increased CARL expression in PVL compared with OL. Conversely, RACK1 and YWHA were highly expressed in oral potentially malignant disorder compared to the control group. Furthermore, significant differences in CALR and RACK1 expression were observed in the OL group when comparing samples with and without oral epithelial dysplasia, unlike the PVL. This research provides insights into the molecular mechanisms underlying these conditions and highlights potential targets for future diagnostic and therapeutic approaches.

Correlation of Bcl-2 expression with prognosis and survival in patients with head and neck cancer: A systematic review and meta-analysis.

Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21-2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26-2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34-2.67), while in the larynx it was 1.77 (0.62-5.06), and the DFS in the pharynx was 2.02 (1.46-2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11-1.86) and 1.88 (1.12-3.16), while in DFS it was 1.70 (0.95-3.03) and 2.08 (1.55-2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60-2.37) and DFS was 1.48 (0.91-2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47-3.52) and DFS of 2.77 (1.74-4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study.

Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Genetic linkage analysis of head and neck cancer in a Spanish family.

OBJECTIVES: To describe the genetic variants that may be associated with the development of head and neck cancer (HNC) and functionally validating the molecular implications. MATERIALS AND METHODS: A prospective observational study was carried out on a family of 3 generations in which 3 members had developed HNC. Peripheral blood sample was taken in a routine procedure for exome sequencing in one relative and genotyping in the remaining twelve relatives. For the functional analysis all-trans retinoic acid (atRA) was extracted from saliva and serum and measured using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The presence of HPV-DNA. RESULTS: None of the patients smoked or consumed alcohol. The presence of HPV DNA was not detected in any of the biopsied samples. A total amount of 6 members out of 13 (46.15%) carried out the same mutation of CYP26B1 (2p13.2; G>T). The mean plasma concentration of atRA was 3.3109 ± 1.4791 pg/mL for the study family and 4.7370 ± 1.5992 pg/mL for the controls (p = 0.042). CONCLUSION: Lower levels of atRA were confirmed in the study family, which may open the way to the possible relationship between the polymorphism CYP26B1 (2p13.2; G>T) and HNC.

Protein-based salivary biomarkers for the diagnosis of periodontal diseases: Systematic review and meta-analysis.

Objective: This systematic review and meta-analysis was aimed at determining differentially expressed protein-based biomarkers detectable in the saliva for the diagnosis of major periodontal diseases. Methods: A literature review was conducted through January 31, 2022. The methodological quality and risk of bias were assessed with the Newcastle-Ottawa scale for case-control studies. Heterogeneity among studies was analysed with the Q statistical test and the I2 test. p-values lower than 0.10 and I2 values higher than 50% indicated high heterogeneity among studies; therefore, the random-effects model was used. The analysis of biological pathways associated with the differentially expressed protein markers was performed with the STITCH integration analysis tool and was limited to interactions with high confidence levels (0.7). Results: Of all protein-based biomarkers detected, 12 were suitable for meta-analysis: IL-1ß, MIP-1α, albumin, TNF-α, ICTP, Ig-A, lactoferrin, MMP-8, IL-6, IL-8, IL-17 and PGE2. The salivary markers with high applicability were IL-1ß for differentiating patients with chronic periodontal disease from patients with gingivitis with an OE = 73.5 pg/mL; ICTP for differentiating patients with chronic periodontal disease from healthy control patients with an OE = 0.091 ng/mL; and PGE2 for differentiating patients with chronic periodontal disease from healthy control patients with an OE = 36.3 pg/mL. Conclusions: The biomarkers with the highest differential expression and the greatest potential for clinical applicability are IL-1ß for differentiating periodontitis from gingivitis, and ICTP and PGE2 for differentiating periodontitis from healthy status.

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.

Quantitative proteomics in medication-related osteonecrosis of the jaw: A proof-of-concept study.

OBJECTIVE: Medication-related osteonecrosis of the jaw (MRONJ) is a paradoxical effect associated with bone-modifying agents (BMAs) and other drugs. Currently, no valuable diagnostic or prognosis biomarkers exist. The goal of this research was to study MRONJ-related salivary proteome. MATERIALS AND METHODS: This case-control aimed to study salivary proteome in MRONJ versus control groups (i) formed from BMAs consumers and (ii) healthy individuals to unravel biomarkers. Thirty-eight samples of unstimulated whole saliva (18 MRONJ patients, 10 BMA consumers, and 10 healthy controls) were collected. Proteomic analysis by SWATH-MS coupled with bioinformatics analysis was executed. RESULTS: A total of 586 proteins were identified, 175 proteins showed significant differences among MRONJ versus controls. SWATH-MS revealed differentially expressed proteins among three groups, which have never been isolated. These proteins had distinct roles including cell envelope organization, positive regulation of vesicle fusion, positive regulation of receptor binding, or regulation of low-density lipoprotein particle clearance. Integrative analysis prioritized 3 proteins (MMP9, AACT, and HBD). Under receiver-operating characteristic analysis, this panel discriminated MRONJ with a sensitivity of 90% and a specificity of 78.9%. CONCLUSION: These findings may inform a novel biomarker panel for MRONJ prediction or diagnosis. Nonetheless, further research is needed to validate this panel.

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.

Immunoexpression profile of hypoxia-inducible factor (HIF) targets in potentially malignant and malignant oral lesions: a pilot study

Abstract Oral potentially malignant disorders (OPMD) are associated with an increased risk of oral squamous cell carcinoma (OSCC). OSCC has an aggressive profile and is the most prevalent among different head and neck malignancies. Most OSCC patients are diagnosed with advanced stage tumors and have a poor prognosis. Cancer cells are able to reprogram their metabolism, even in the presence of oxygen, enhancing the conversion of glucose to lactate via the glycolytic pathway, a phenomenon mainly regulated by hypoxia-inducible factor (HIF) signaling. Thus, several glycometabolism-related biomarkers are upregulated. Objectives This study aimed to evaluate the immunoexpression of the HIF targets GLUT1, GLUT3, HK2, PFKL, PKM2, pPDH, LDHA, MCT4, and CAIX in OPMD and OSCC samples, in order to identify potential correlations between biomarkers' immunoexpression, clinicopathological features, and prognostic parameters. Methodology OSCC and OPMD samples from 21 and 34 patients (respectively) were retrospectively collected and stained for the different biomarkers by immunohistochemistry. Results CAIX and MCT4 expressions were significantly higher in OSCC samples when compared with OPMD samples, while the rest were also expressed by OPMD. GLUT3 and PKM2 alone, and the concomitant expression of more than four glycometabolism-related biomarkers were significantly correlated with the presence of dysplasia in OPMD. When considering OSCC cases, a trend toward increased expression of biomarkers and poor clinicopathological features was observed, and the differences regarding HK2, PFKL, LDHA and MCT4 expression were significant. Moreover, HK2 and CAIX were correlated with low survival rates. GLUT1 and GLUT3 were significantly associated with poor outcome when their expression was observed in the hypoxic region of malignant lesions. Conclusion OPMD and OSCC cells overexpress glycolysis-related proteins, which is associated with aggressive features and poor patient outcome. Further research is needed to deeply understand the glycolic phenotype in the process of oral carcinogenesis.

Caspase 3 and Cleaved Caspase 3 Expression in Tumorogenesis and Its Correlations with Prognosis in Head and Neck Cancer: A Systematic Review and Meta-Analysis.

Head and neck cancer (HNC) is an ascending and agressive disease. The search for new molecular markers is emerging to solve difficulties in diagnosis, risk management, prognosis and effectiveness of treatments. Proteins related to apoptotic machinery have been identified as potential biomarkers. Caspase 3 is the main effector caspase and has a key role in apoptosis. The objective of this systematic review and meta-analysis is to review studies that analyze changes in Caspase 3 and Cleaved Caspase 3 expression both in oral premalignant disorders (OPMD) as well as in head and neck cancer (HNC). This study also proposes to review the prognostic values associated with HNC according to the expression of Caspase 3. Medline (via PubMed), EMBASE, Scopus, Cochrane, Web of Science and Grey Literature Database were screened from inception to june of 2022 and 18 studies were selected and 8 were included in the prognostic meta-analysis. Results related to the comparison of Caspase 3 expression demonstrated similar expression of Caspase 3 in HNC, with an average of 51.9% (9.5-98.1) showing high/moderate expression compared to 45.7% (14.6-84.7) in OPMD. Of interest, Cleaved Caspase 3 resulted incresed in HNC when compared with OPMD, being 73.3% (38.6-88.3) versus 22.9% (7.1-38.7). Pooled Fixed effect of HR values (95% CI) for OS related to Caspase 3 IHC expression in HNC patients was 1.48 (95% CI 0.95-2.28); also, the rate of heterogeneity was low, as revealed by I2 = 31%. For DFS was 1.07 (95% CI 0.79-1.45) with I2 = 0% and DSS showed a HR of 0.88 (95% CI 0.69-1.12) with I2 = 37%. Caspase 3 and Cleaved Caspase 3 expression could be linked with malignancy progression, but the expression of Caspase 3 did not influence the prognosis of patients with HNC.

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.

Use of the Fractal Dimension to Differentiate Epithelium and Connective Tissue in Oral Leukoplakias.

BACKGROUND: Oral leukoplakia (OL) is considered one of the most common potentially malignant oral disorders (OPMD), with a verified increased risk of developing oral cancer. The identification of the dysplasia grade (low-high) is the only consolidated factor used to evaluate this risk. The objective of this study was to verify the role of the fractal dimension (FD) in assessing this dysplasia. METHODS: To begin, 29 OL and 10 normal oral mucosa (NOM) biopsies were retrieved for FD analysis of the epithelial (dime) and the connective (dimc) tissue. RESULTS: In the OL group, the median value of dime is higher (1.67, IQR = 0.12) than for the NOM group (1.56, IQR = 0.08), with statistically significant differences (Wilcoxon test, p = 0.0031). There were no differences in relation to dimc. Significant differences were observed between the non-dysplasia vs. high-grade (p = 0.0156) and low-grade vs. high-grade (p = 0.0049) groups. No significant differences were identified in relation to dimc for the different degrees of dysplasia. For a cut-off point of 1.44 of dime, a specificity of 96.6% was obtained, a sensitivity of 100%, and an AUC = 0.819 (p = 0.003). CONCLUSIONS: FD at the level of the epithelium may be used as a diagnostic tool in OL.

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.

Efficacy of different sentinel lymph node biopsy protocols in oral squamous cell carcinoma: Systematic review and meta-analysis.

The sentinel node biopsy (SNB) is highly protocolized in other cancers, however, this is not the case for oral squamous cell carcinoma patients, hence our objective was to evaluate the different protocols published. A specific study protocol was designed and subsequently registered on PROSPERO (Ref. CRD42021279217). Twenty-three articles were included in the meta-analysis. The grouped sensitivity of the SNB was 82% (95% CI: 0.74-0.88), and the grouped specificity was 100% (95% CI: 0.99-1.00). The use of other radiotracers other than pre-operative lopamidol showed higher values of sensitivity of 82.80% (95% CI: 76.90%-87.50%; p < 0.001). The use of the blue dye stain showed higher sensitivity values of 85.60% (95% CI: 71.90%-93.20%), compared to sensitivity values of 77.50% when it was not used (95% CI: 69.10%-84.20%) (p < 0.001). Diagnostic rates are variable and they were significantly better when 99mTc was used in all its variations and accompanied by the blue dye staining.

Efficacy of Ciprofloxacin, Metronidazole and Minocycline in Ordered Mesoporous Silica against Enterococcus faecalis for Dental Pulp Revascularization: An In-Vitro Study.

Pulp revascularization of teeth with necrotic pulp has become an alternative treatment in cases with immature apex. Microbial control is essential to achieve a successful outcome and continued root development. Enterococcus faecalis (E. faecalis) is the most frequently isolated bacterial species in root canals of endodontically failed teeth. Our main goal was to compare the in-vitro antimicrobial efficacy of different antibiotic formulations delivered by ordered mesoporous silica (OMS) against E. faecalis. To determine antibiotic susceptibility, we tested OMS and triple antibiotic paste (TAP; ciprofloxacin:metronidazole:minocycline) with different reagents in different concentrations, using the Kirby−Bauer disk diffusion method. OMS and metronidazole showed no antibacterial activity against E. faecalis. Mixtures of OMS and antibiotics in proportions of 2:2:14 and 4:1:7 (mg/L of ciprofloxacin:metronidazole:minocycline, respectively) showed the lowest antibacterial activity. The antibacterial activity of the combined solutions of ciprofloxacin and metronidazole was significantly higher (p < 0.005). Combinations in different concentrations of minocycline, ciprofloxacin, and metronidazole in OMS have shown activity against E. faecalis, although the combined use of ciprofloxacin and metronidazole has shown the most effective results. This study demonstrates the efficacy of intracanal antibiotic combination paste activity against E. faecalis, avoiding the use of minocycline, whose undesirable effect of teeth staining is a common problem for patients and professionals in dental clinic.

Influence of loading and drilling on marginal bone loss around implants with a Dynamic Bone Management design: A single-blind, randomised, 12-month clinical trial.

PURPOSE: To evaluate marginal bone loss 6 and 12 months after prosthetic loading of implants with Dynamic Bone Management (Straumann, Basel, Switzerland) through the implementation of different drilling protocols. MATERIALS AND METHODS: A balanced, randomised, single-blind clinical trial was conducted with four parallel experimental arms: immediate loading and under-drilling, immediate loading and complete drilling, early loading and under-drilling, and early loading and complete drilling. Forty-four implants with a Dynamic Bone Management design and with a diameter of 3.75 mm and a length of 10.00 mm were placed in healed mature bone (more than 6 months post-extraction). RESULTS: The mean primary stability achieved was 60.6 ± 12.2 implant stability quotient, with a range from 21 to 75, and no differences were observed when considering the drilling protocol used, bone type or location. Early loading resulted in a loss of 0.728 mm (standard error 0.212; 95% confidence interval 1.134 to -0.325; t value -3.440), whereas immediate loading did not result in any bone loss. When the interaction between the loading and drilling protocols was studied, performing the complete drilling protocol in conjunction with early implant loading was found to result in lower marginal bone loss, with a marginal bone gain effect of 0.814 mm (standard error 0.283; 95% confidence interval -0.274 to 1.353; t value 2.880). CONCLUSIONS: Use of the complete drilling protocol in conjunction with early implant loading resulted in the lowest marginal bone loss at 12 months.