Chronic Sclerosing Sialadenitis of the Submandibular Gland and its Histopathological Spectrum in the IgG4-Related Disease: a Series of 17 Cases.

PURPOSE: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease. METHODS: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected. RESULTS: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease. CONCLUSION: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD.

Cholesterol depletion induces mesenchymal properties in oral squamous cell carcinoma cell line.

BACKGROUND: Cholesterol in cell membranes is crucial for cell signaling, adhesion, and migration. Membranes feature cholesterol-rich caveolae with caveolin proteins, playing roles in epithelial-mesenchymal transition and cancer progression. Despite elevated cholesterol levels in tumors, its precise function and the effects of its depletion in oral squamous cell carcinoma remain unclear. The aim of this study was to evaluate the influence of cholesterol depletion in oral squamous cell carcinoma cell line and epithelial-mesenchymal transition process. METHODS: Cholesterol depletion was induced on SCC-9 cells by methyl-ß-cyclodextrin and cell viability, proliferation, apoptosis, and colony formation capacities were evaluated. Gene and protein expressions were evaluated by reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot, respectively, and cell sublocalization was assessed by immunofluorescence. RESULTS: Cholesterol depletion resulted in alteration of oral squamous cell carcinoma cell morphology at different concentrations of methyl-ß-cyclodextrin, as well as decreased cell proliferation and viability rates. Analysis of CAV1 transcript expression revealed increased gene expression in the treated SCC-9 during the 24 h period, at different concentrations of methyl-ß-cyclodextrin: 5 , 7.5, 10, and 15 mM, in relation to parental SCC-9. CAV1 protein expression was increased, with subsequent dose-dependent decrease. A statistically significant difference was observed in samples treated with 5 mM of methyl-ß-cyclodextrin (p = 0.02, Kruskal-Wallis test). The immunofluorescence assay showed lower cytoplasmic and membrane labeling intensity in the treated samples for CAV1. CONCLUSION: These findings indicate the modulation of cholesterol as a possible mechanism underlying the regulation of these molecules and activation of epithelial-mesenchymal transition in oral squamous cell carcinoma.

E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST contribute to epithelial-mesenchymal transition in salivary gland tumors.

BACKGROUND: Transcription factors are important in the epithelial-mesenchymal transition process and are possibly related to the development of a more invasive tumor phenotype. Thus, the objective of this study was to analyze the expression and identify the localization of cellular markers related to the epithelial-mesenchymal transition process in salivary gland tumors. STUDY DESIGN: The expression and localization of E-CADERIN, N-CADERIN, SLUG, SNAIL, and TWIST were evaluated, using immunohistochemistry, in 48 salivary gland tumors, being 17 pleomorphic adenomas (PA), 14 adenoid cystic carcinomas (ACC), and 17 mucoepidermoid carcinomas (MEC). these proteins were compared to clinical and histopathologic parameters. normal gland tissues were included for immunohistochemical comparisons. RESULTS: ACC and MEC cases showed higher expression of SNAIL compared to PA. MEC showed high expression of SLUG and TWIST. Low expression of N-CADHERIN, SNAIL, and TWIST in ACC was frequent in T3 and T4. High expression of TWIST in MEC was more frequent at age ≥ 40 years A positive correlation was only observed between N-cadherin/SNAIL in ACC, between SNAIL/TWIST in MEC, and between SLUG/TWIST in PA. CONCLUSION: This study provided insight into EMT-related proteins (E-cadherin, N-cadherin, SNAIL, SLUG, and TWIST) and their contribution to the maintenance of morphogenesis and the development of the salivary gland tumors and showed a positive correlation among N-CADHERIN/SNAIL in ACC and SNAIL/TWIST in MEC.

DNA content and clinicopathological features aid in distinguishing ameloblastic carcinoma from ameloblastoma.

BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.

Influence of keratinized mucosa on peri-implant diseases: a retrospective cohort study in humans.

OBJECTIVE: The present study aimed to assess the relationship between keratinized mucosa width and peri-implant diseases, namely peri-implant mucositis and peri-implantitis. MATERIALS AND METHODS: Ninety-one dental implants in function for ≥ 6 months from 40 partially or completely edentulous non-smoker subjects (24 females and 16 males) were evaluated clinically and radiographically. The width of keratinized mucosa, probing depth, plaque index, bleeding on probing, and marginal bone levels were assessed. Keratinized mucosa width was categorized as ≥ 2 mm or < 2 mm. RESULTS: There was no statistically significant association between keratinized buccal mucosa width and peri-implant mucositis or peri-implantitis (p ≥ 0.37). In the regression analysis, peri-implantitis was associated with longer implant function time (RR: 2.55, 95% CI: 1.25-11.81, p = 0.02) and implants in the maxilla (RR: 3.15, 95% CI: 1.61-14.93, p = 0.003). Mucositis was not associated with any of the factors analyzed. CONCLUSION: In conclusion, in the present sample, keratinized buccal mucosa width was not associated with peri-implant diseases, suggesting that a band of keratinized mucosa may not be necessary to maintain peri-implant health. Prospective studies are required to better understand its role in the maintenance of peri-implant health.

Could fluoride be considered a genotoxic chemical agent in vivo? A systematic review with meta-analysis.

The goal of this study was to perform systematic review (SR) to investigate the scientific literature regarding the genotoxicity effects of fluoride exposure (FE). The search of databases used for this study was PubMed/Medline, SCOPUS and Web of Science. The quality of included studies was assessed using the EPHPP (Effective Public Health Practice Project). A total of 20 potentially relevant studies were selected for evaluating the genotoxicity induced by fluoride. Few studies have revealed that FE induces genotoxicity. A total of 14 studies demonstrated negative results whereas 6 studies did not. After reviewing the twenty studies, 1 was classified as weak, 10 were considered moderate and 9 were considered strong, according to the EPHPP. Taken together, it has been established that genotoxicity of fluoride is limited.

Oral carcinoma in situ in a middle-aged woman with systemic sclerosis: Report of a rare case and literature review.

Systemic sclerosis (SSc) is a rare multisystem rheumatic autoimmune disease involving the skin, connective tissue, and internal organs. Individuals with SSc are at increased risk of cancer. We herein contribute by reporting a case of carcinoma in situ affecting the lower lip and labial mucosa of a 56-year-old Brazilian female patient, which apparently represents the first case reported in Latin America. Surgical resection of the lesion was performed. After a 2-year follow-up, the patient has shown no evidence of recurrence. According to a literature review in PubMed, Web of Science, Scopus, and Embase databases on SSc-related oral and oropharyngeal cancer, 11 cases have been documented hitherto. Reports of oral carcinoma in individuals with SSc are rare. Clinicians should conduct regular examinations of the oral mucosa of these individuals to permit an early diagnosis, as done in the present case.

Are Cytomorphogenetic Events Correlated with Oral Mucosal Lesions Induced by Crack Cocaine Use? A Systematic Review.

The aim of this systematic review was to answer the question of whether crack cocaine can induce cellular and molecular alterations and whether such alterations are somehow related to clinical lesions in the oral mucosa. The searches were undertaken in three electronic databases and conducted based on the PRISMA 2020 statement. Eleven studies published between 1994 and 2020 were analyzed. The quality of the included studies was assessed by two independent reviewers (TGP and DAR) through a confounder's categorization methodology, in which final ratings were attributed (strong, moderate or weak) for each study. From 11 studies included, 7 evaluated the cellular/molecular impact of the addiction in a total of 492 individuals and compared to a control (non-exposure) group (n = 472). The main tests used for cellular alteration were MN and AgNORs. Cells from crack cocaine groups exhibited increased proliferation and MN counting. Only four studies evaluated the prevalence of oral lesions. All of them showed that individuals exposed to crack cocaine presented an increased number of oral lesions. Most studies showed good quality. In conclusion, our results demonstrate that crack use may induce changes at the cellular and molecular level and also exhibit an increased number of oral lesions. However, a correlation between such changes and oral mucosa lesions still needs further investigation and elucidation through other clinical studies in humans.

Contribution of public oral pathology services to the diagnosis of oral and oropharyngeal cancer in Brazil.

This study aimed to evaluate the contribution of oral and maxillofacial pathology laboratories (OMPLs) in Brazilian public universities to the diagnosis of lip, oral cavity, and oropharyngeal squamous cell carcinoma (SCC). A cross-sectional study was performed using biopsy records from a consortium of sixteen public OMPLs from all regions of Brazil (North, Northeast, Central-West, Southeast, and South). Clinical and demographic data of patients diagnosed with lip, oral cavity, and oropharyngeal SCC between 2010 and 2019 were collected from the patients' histopathological records. Of the 120,010 oral and maxillofacial biopsies (2010-2019), 6.9% (8,321 cases) were diagnosed as lip (0.8%, 951 cases), oral cavity (4.9%, 5,971 cases), and oropharyngeal (1.2%, 1,399 cases) SCCs. Most cases were from Brazil's Southeast (64.5%), where six of the OMPLs analyzed are located. The predominant profile of patients with lip and oral cavity SCC was Caucasian men, with a mean age over 60 years, low schooling level, and a previous history of heavy tobacco consumption. In the oropharyngeal group, the majority were non-Caucasian men, with a mean age under 60 years, had a low education level, and were former/current tobacco and alcohol users. According to data from the Brazilian National Cancer Institute, approximately 9.9% of the total lip, oral cavity, and oropharyngeal SCCs reported over the last decade in Brazil may have been diagnosed at the OMPLs included in the current study. Therefore, this data confirms the contribution of public OMPLs with respect to the important diagnostic support they provide to the oral healthcare services extended by the Brazilian Public Health System.

Clinicopathological Features of Metastasis to the Oral and Maxillofacial Region-Multicenter Study.

BACKGROUND: This study aimed to investigate the clinicopathological features of metastases in the oral and maxillofacial regions. METHODS: In this retrospective study, biopsy records were obtained from referral centers for oral and maxillofacial diagnosis in Brazil, Guatemala, Mexico, and South Africa. RESULTS: A total of 120 cases were evaluated. Of these, 53.78% affected female patients, with a mean age of 57.64 years. Intraosseous lesions were more frequent, particularly in the posterior region of the mandible (49.58%). Clinically, most cases presented with symptomatic swelling, with an average evolution time of 25 months. The clinical diagnostic hypothesis in most instances was that of a malignant lesion. Breast cancer was the most common primary tumor location in females, while lung origin was most common in males. In most cases, the primary cancer was an adenocarcinoma (44.73%). The follow-up period was available for 29 cases, and out of these, 20 had died due to the disease. CONCLUSION: Although this is a rare condition, clinicians should be aware that any oral lesions have the possibility of being metastatic, particularly in individuals with a previous history of cancer. The findings from this study could assist clinicians in prompt diagnosing these lesions and subsequent conducting oncologic assessments and treatment.

Photodynamic therapy as adjunctive treatment of single-rooted teeth in patients with grade C periodontitis: A randomized controlled clinical trial.

BACKGROUND: The present study aimed to evaluate the adjunctive effect of an antimicrobial photodynamic therapy (aPDT) protocol on single-rooted teeth of patients with grade C periodontitis. METHODS: Sixty-four single-rooted teeth (14 patients) were included in each group of this double-blinded split-mouth randomized clinical trial. The teeth were randomly divided into scaling and root planing + aPDT (test group) and scaling and root planing+sham aPDT (control group). The aPDT protocol consisted of incubation with 1% methylene blue for 5 min, rinsing, and application of a diode laser (wavelength of 660 nm, power of 100 mW) for 10 s. aPDT was repeated after 7 days. Bleeding on probing (BoP), probing depth (PD), gingival recession (GR), and clinical attachment loss (CAL) were recorded before and 3 months after treatment. A 5% significance level was adopted for statistical analysis. RESULTS: Final PD was significantly (P = 0.02) lower in the test group (2.87 ± 1.40 mm) compared to control (3.12 ± 1.69 mm). The test group showed a significantly higher percentage of sites with PD≤4 mm and concomitant BoP compared to control (91%x86%;P < 0.001). At sites with baseline PD>4 mm, final PD and CAL were significantly (P = 0.01) lower in the test group (4.11 ± 1.66 and 4.89 ± 2.49 mm, respectively) compared to control (4.88 ± 1.99 and 5.89 ± 2.74 mm, respectively). CONCLUSIONS: aPDT combined with scaling and root planning provided slightly better periodontal clinical results than the latter procedure alone, exerting a superior effect at sites with greater baseline PD. aPDT might be used as adjunctive treatment in grade C periodontitis affecting single-rooted teeth since it improves the response to conventional periodontal treatment.

Effects of Violet and IR LED Light on mast cell degranulation: in vivo study in a murine model.

The aim of this study was to evaluate the influence of IR (λ850 ± 10 nm) and violet (λ405 ± 10 nm) LED phototherapy on total mast cells counts and its ability to influence mast cell degranulation. For this, 27 Wistar rats were used and were randomly distributed into three groups: control, IR LED, and violet LED. When indicated, irradiation done and they were sacrificed, had their tongue removed immediately, 20-min, 45-min, and 2-h after irradiation. Samples were processed to wax, cut, and stained with Toluidine Blue. Intact and degranulated mast cells were counted under light microscopy, and statistical analysis was carried out. In the superficial connective tissue and muscular tissues, violet LED light caused a significant increase in both total number and degranulated mast cells when compared to the control group immediately after irradiation. The degranulation indexes were higher in the groups irradiated with Violet light, both in superficial connective tissue and muscular tissues in relation to the timing. Irradiation with IR LED caused immediate increase in the total number and degranulated of mast cells when compared to the control group only in the superficial connective tissue. In all times observed, the highest total amount of mast cells was seen immediately after irradiation, except in the muscular tissue, which presented the highest amount after 20-min. It was concluded that IR and violet LED light were able to increase the number of mast cells and inducing degranulation in oral mucosa. However, considering that violet LED light can be harmful in periodontal disease, it seems that the use of IR LED light could be the best option in Dentistry.

Can SARS-CoV-2 screening in oral biopsies aid epidemiological surveillance?

BACKGROUND: Three years after the first confirmed COVID-19 case in Brazil, the outcomes of Federal government omissions in managing the crisis and anti-science stance heading into the pandemic have become even more evident. With over 36 million confirmed cases and nearly 700 000 deaths up to January 2023, the country is one of the hardest-hit places in the world. The lack of mass-testing programs was a critical broken pillar responsible for the quick and uncontrolled SARS-CoV-2 spread throughout the Brazilian population. Faced with this situation, we aimed to perform the routine SARS-CoV-2 screening through RT-qPCR of oral biopsies samples to aid in the asymptomatic epidemiological surveillance during the principal outbreak periods. METHODS: We analyzed 649 formalin-fixed paraffin-embedded oral tissue samples from five important oral and maxillofacial pathology laboratories from the north, northeast, and southeast geographic regions of Brazil. We also sequenced the whole viral genome of positive cases to investigate SARS-CoV-2 variants. RESULTS: The virus was detected in 9/649 analyzed samples, of which three harbored the Variant of Concern Alpha (B.1.1.7). CONCLUSION: Although our approach did not value aiding asymptomatic epidemiological surveillance, we could successfully identify a using FFPE tissue samples. Therefore, we suggest using FFPE tissue samples from patients who have confirmed diagnosis of SARS-CoV-2 infection for phylogenetic reconstruction and contraindicate the routine laboratory screening of these samples as a tool for asymptomatic epidemiological surveillance.

Heterogeneity and versatility of the extracellular matrix during the transition from pleomorphic adenoma to carcinoma ex pleomorphic adenoma: cumulative findings from basic research and new insights.

Pleomorphic adenoma (PA) is the most common salivary gland tumor, accounting for 50%-60% of these neoplasms. If untreated, 6.2% of PA may undergo malignant transformation to carcinoma ex-pleomorphic adenoma (CXPA). CXPA is a rare and aggressive malignant tumor, whose prevalence represents approximately 3%-6% of all salivary gland tumors. Although the pathogenesis of the PA-CXPA transition remains unclear, CXPA development requires the participation of cellular components and the tumor microenvironment for its progression. The extracellular matrix (ECM) comprises a heterogeneous and versatile network of macromolecules synthesized and secreted by embryonic cells. In the PA-CXPA sequence, ECM is formed by a variety of components including collagen, elastin, fibronectin, laminins, glycosaminoglycans, proteoglycans, and other glycoproteins, mainly secreted by epithelial cells, myoepithelial cells, cancer-associated fibroblasts, immune cells, and endothelial cells. Like in other tumors including breast cancer, ECM changes play an important role in the PA-CXPA sequence. This review summarizes what is currently known about the role of ECM during CXPA development.

Epithelial salivary gland tumors in pediatric patients: An international collaborative study.

OBJECTIVE: Salivary gland tumors (SGT) are a diverse group of uncommon neoplasms that are rare in pediatric patients. This study aimed to characterize the clinicopathological profile of pediatric patients affected by SGT from a large case series derived from an international group of academic centers. STUDY DESIGN: A retrospective analysis of pediatric patients with SGT (0-19 years old) diagnosed between 2000 and 2021 from Brazil, South Africa, and the United Kingdom was performed. SPSS Statistics for Windows was used for a quantitative analysis of the data, with a descriptive analysis of the clinicopathological characteristics and the association between clinical variables and diagnoses. RESULTS: A total of 203 cases of epithelial SGT were included. Females were slightly more commonly (56.5%), with a mean age of 14.1 years. The palate was the most common site (43.5%), followed by the parotid gland (29%), lip (10%), and submandibular gland (7.5%). The predominant clinical presentation was a flesh-colored, smooth, and painless nodule. Pleomorphic adenoma (PA) was the most frequently diagnosed SGT (58.6%), followed by mucoepidermoid carcinoma (MEC) (26.6%). Surgery (90.8%) was the favored treatment option. CONCLUSIONS: Benign SGT in pediatric patients are more commonly benign than malignant tumors. Clinicians should keep PA and MEC in mind when assessing nodular lesions of possible salivary gland origin in pediatric patients.

Photodynamic therapy as an adjunctive treatment for Grade C periodontitis in molar teeth: a preliminary trial.

OBJECTIVE: The present study aimed to evaluate the local effect of antimicrobial photodynamic therapy (aPDT) as adjunctive treatment for Grade C periodontitis in molars teeth. METHOD AND MATERIALS: Thirty-eight molar teeth from 11 patients were included in this split-mouth randomized clinical trial. The teeth were randomly divided into two groups (n = 19 each) that were submitted to conventional scaling and root planing in addition to aPDT (test group) and to scaling and root planing in addition to aPDT simulation (control group). The following periodontal parameters were obtained prior to treatment (baseline) and at 3 months after the intervention: bleeding on probing, probing depth, gingival recession, clinical attachment level, and furcation level. A 5% significance level was adopted in the statistical analysis. RESULTS: Both groups exhibited improvement in the clinical parameters (P < .001). However, the reductions in bleeding on probing and probing depth were greater in the test group (P < .001). There were no significant differences in the other clinical parameters between groups (P ≥ .130). CONCLUSIONS: Molar teeth treated with aPDT and scaling and root planing showed superior clinical improvement compared to those submitted only to scaling and root planing. aPDT may be used as adjunctive treatment for Grade C periodontitis affecting molar teeth since it seems to improve the clinical response to conventional debridement.

Synchronous odontogenic tumors: A systematic review.

This systematic review aimed to incorporate published information about synchronous odontogenic tumors (SOTs) with an analysis of the demographic and clinical characteristics from the cases published in the literature. Case reports and case series of SOT were searched in PubMed, Web of Science, Scopus, and EMBASE. A descriptive statistical analysis was performed. Twenty-eight studies comprising 30 cases of SOTs were included. Considering all cases published, SOTs mostly occurred simultaneously in the maxilla and mandible (n = 19/63.3%). Lesions were bifocal in 13 (43.3% of all the 30 cases) and multifocal in 17 cases (56.7% of all the 30 cases). All SOTs available in the literature presented the same type of lesion, and two of them also involved another different SOT (n = 2/6.7% of all the 30 cases). Out of all published cases, the most frequent SOTs in the literature were odontomas (n = 10/33.3% of all the 30 cases), squamous odontogenic tumors (OTs) (n = 8/26.7% of all the 30 cases), calcifying epithelial OTs (n = 8/26.7% of all the 30 cases), and adenomatoid OTs (n = 2/6.7% of all the 30 cases). Considering all SOTs cases included, the overall recurrence was 13.3%. Inside a subgroup of the lesion, synchronous calcifying epithelial OT presented the highest (25%). Five cases (16.7% of all the 30 cases) had a previously associated syndrome, with two cases of Schimmelpenning syndrome being reported. Among published SOTs, odontomas were the most common. All SOTs available in the scientific literature showed the same type of OT and mainly affected both jaws simultaneously. Only a few of these cases were associated with a syndrome.

Impact of serum vitamin D levels on periodontal healing outcomes: A preliminary cohort study.

OBJECTIVE: To evaluated the relationship between serum vitamin D levels and periodontal healing outcomes in patients with mild or moderate periodontitis. METHODS: Serum vitamin D levels and periodontal pockets and gingival bleeding were evaluated in 51 patients before and 6 months after non-surgical periodontal treatment. A t-test and chi-square test were used to analyse the data (p ≤ 0.05). RESULTS: The mean reduction of periodontal pocket depth was statistically significant higher in patients with vitamin D ≥30 ng/ml than those with <30 ng/ml (CI = -0.23-0.42, p = 0.05), but not clinically significant. Vitamin D level was not associated with the percentage of sites of gingival bleeding on probing at the final evaluation (OR = 0.58, 95% CI = 0.17-1.99, p = 0.39). CONCLUSION: Lower serum vitamin D level was associated with a slightly reduced periodontal healing after non-surgical periodontal therapy, which should be further investigated in a larger population.

Salivary biomarkers to evaluate psychological disorders in oral lichen planus: A systematic review with meta-analysis.

OBJECTIVE: To analyze the use of salivary biomarkers to identify psychological disorders (anxiety, depression, and stress) in individuals with oral lichen planus (OLP). MATERIALS AND METHODS: The search was made in Medline/Pubmed, Scopus, Web of Science, Virtual Health Library, ProQuest, and by cross-reference. Original case-control, cross-sectional, and cohort studies, in human subjects (age ≥18 years) with clinical and histopathological diagnosis, with or without the use of psychometric scales, published until June 2021, were included. Random-effects meta-analyses, subgroup analyses, and sensitivity were performed. Publication bias was measured using the Egger test and visual inspection of the funnel plot. RESULTS: A total of 67 articles were found, of which 12 were included in the meta-analysis. Among the different biomarkers identified, it was only possible to perform a meta-analysis for cortisol. The mean difference between salivary cortisol levels in patients with OLP compared to controls was 3.43 ng/ml (95% CI: 1.20-5.65) with I2  = 98.9%. Studies considered outliers were removed and based on sensitivity analyses, results did not change, therefore, being stable. CONCLUSION: The studies analyzed demonstrated that cortisol was the most quantified biomarker to identify psychological disorders; however, DHEA, IgA, adiponectin, and α-amylase were also evaluated.