An Evidence-Based Update on the Potential for Malignancy of Oral Lichen Planus and Related Conditions: A Systematic Review and Meta-Analysis.

A systematic review and a meta-analysis is presented on published articles on the malignant transformation of oral lichen planus (OLP) and related conditions, which, based on current evidence, updates an earlier systematic review published by our research group that included publications until November 2018. In this updated study (Nov-2023) we searched MEDLINE, Embase, Web of Science, and Scopus. We evaluated the methodological quality of studies (QUIPS tool) and carried out meta-analyses. The inclusion criteria were met by 101 studies (38,083 patients), of which, 20 new primary-level studies (11,512 patients) were published in the last 5 years and were added to our updated study. The pooled malignant transformation ratio was 1.43% (95% CI = 1.09-1.80) for OLP; 1.38% (95% CI = 0.16-3.38) for oral lichenoid lesions; 1.20% (95% CI = 0.00-4.25) for lichenoid reactions; and 5.13% (95% CI = 1.90-9.43) for OLP with dysplasia. No significant differences were found between the OLL or LR groups and the OLP subgroup (p = 0.853 and p = 0.328, respectively), and the malignant transformation was significantly higher for the OLP with dysplasia group in comparison with the OLP group (p = 0.001). The factors that had a significant impact with a higher risk of malignant transformation were the presence of epithelial dysplasia, a higher methodological quality, the consumption of tobacco and alcohol, the location of lesions on the tongue, the presence of atrophic and erosive lesions, and infection by the hepatitis C virus. In conclusion, OLP behaves as an oral potentially malignant disorder (OPMD), whose malignancy ratio is probably underestimated as a consequence essentially of the use of inadequate diagnostic criteria and the low methodological quality of the studies on the subject.

Efficacy of Chlorhexidine after Oral Surgery Procedures on Wound Healing: Systematic Review and Meta-Analysis.

Our objective was to evaluate qualitatively and quantitatively, through a systematic review and meta-analysis, available evidence on the efficacy of chlorhexidine (CHX) when applied after oral surgery on wound healing and related clinical parameters. MEDLINE/PubMed, Embase, CENTRAL, Web of Science, and Scopus were searched for studies published before January 2023. The quality of the methodology used in primary-level studies was assessed using the RoB2 tool; meta-analyses were performed jointly with heterogeneity and small-study effect analyses. Thirty-three studies and 4766 cases were included. The results point out that the application of CHX was significantly more effective, compared to controls where CHX was not employed, providing better wound healing after oral surgery (RR = 0.66, 95% CI = 0.55-0.80, p < 0.001). Stratified meta-analyses confirmed the higher efficacy of 0.20% CHX gel vs. other vehicles and concentrations (p < 0.001, respectively). Likewise, the addition of chitosan to CHX significantly increased the efficacy of surgical wound healing (p < 0.001). The use of CHX has also been significantly beneficial in the prevention of alveolar osteitis after any type of dental extraction (RR = 0.46, 95% CI = 0.39-0.53, p < 0.001) and has also been effective when applied as a gel for a reduction in pain after the surgical extraction of third molars (MD = -0.97, 95% CI = -1.26 to -0.68, p < 0.001). In conclusion, this systematic review and meta-analysis demonstrate on the basis of evidence that the application of CHX exerts a beneficial effect on wound healing after oral surgical procedures, significantly decreasing the patient's risk of developing surgical complications and/or poor wound healing. This benefit was greater when CHX was used at 0.20% in gel form with the addition of chitosan.

Substance P and Neurokinin-1 Receptor System in Thyroid Cancer: Potential Targets for New Molecular Therapies.

In recent years, numerous approaches have been developed to comprehend the molecular alterations underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for the viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumor cells from apoptosis, triggering invasion and metastasis through the enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumor angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as metastatic lesions, exhibit the overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, paracrine, intracrine, and neuroendocrine processes, including the regulation of tumor burden. Consequently, the secretion of SP from TC results in increased SP levels in plasma, which are significantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumor action. They impair cancer cell proliferation on one side and induce apoptosis of tumor cells on the other side. Furthermore, it has been demonstrated that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

Hypertension in oral lichen planus: A systematic review and meta-analysis.

OBJECTIVES: To perform a systematic review and meta-analysis in order to qualitatively and quantitatively evaluate the prevalence and magnitude of the association of hypertension in patients with oral lichen planus (OLP). METHODS: MEDLINE, Embase, Scopus, and Web of Science databases were searched for studies published before May 2022, not restricted by publication language or date. The methodological quality and risk of bias of primary-level studies were critically assessed. Meta-analyses were performed, as well as meta-regression, stratified, sensitivity and small-study effects analyses, a Galbraith (radial) plot, and trial sequential analysis. Quality of evidence was evaluated using GRADE system. RESULTS: 104 studies, including 16,587 patients, met the inclusion criteria. The results show that patients who suffer from OLP have a high prevalence of hypertension (PP = 24.17%, 95% CI = 21.45-27.00), with a low quality of evidence. A significant association between hypertension and oral lichen planus was also reported (OR = 1.28, 95% CI = 1.01-1.63, p = 0.04), showing a moderate quality of evidence. CONCLUSIONS: Patients with OLP could be at an increased risk of suffering from hypertension which is probably due to multiple factors. Healthcare practitioners involved in OLP management should be aware of this comorbidity in order to apply suitable measures and make referrals if hypertension is suspected, although further research is needed.

Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with oral squamous cell carcinoma (OSCC). We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2022. We evaluated the quality of primary-level studies using the QUIPS tool, conducted meta-analyses, examined inter-study heterogeneity via subgroup analyses and meta-regressions, and performed small-study effects analyses. Fifty primary-level studies (4631 patients) met the inclusion criteria. EGFR overexpression was significantly associated with poor overall survival (hazard ratio [HR] = 1.38, 95% confidence intervals [CI] = 1.06-1.79, p = 0.02), N+ status (odds ratio [OR] = 1.37, 95%CI = 1.01-1.86, p = 0.04), and moderately-poorly differentiated OSCC (OR = 1.43, 95% CI = 1.05-1.94, p = 0.02). In addition, better results were obtained by the application of a cutoff point ≥10% tumor cells with EGFR overexpression (p < 0.001). In conclusion, our systematic review and meta-analysis supports that the immunohistochemical assessment of EGFR overexpression may be useful as a prognostic biomarker for OSCC.

Early Diagnosis of Oral Cancer: A Complex Polyhedral Problem with a Difficult Solution.

Oral and oropharyngeal cancers are a growing problem, accounting for 377,713 and 98,412 new cases per year all over the world and 177,757 and 48,143 deaths annually, respectively. Despite the substantial improvement in diagnostic procedures and treatment techniques in recent years, the mortality rate has not decreased substantially in the last 40 years, which is still close to 50% of cases. The major cause responsible for this high mortality is associated with the high percentage of oral cancers diagnosed in advanced stages (stages III and IV) where the treatment harbors poor efficacy, resulting in challenges, mutilations, or disability. The main reason for cancer to be diagnosed at an advanced stage is a diagnostic delay, so it is critical to reduce this delay in order to improve the prognosis of patients suffering from oral cancer. The causes of oral cancer diagnostic delay are complex and concern patients, healthcare professionals, and healthcare services. In this manuscript, oral cancer diagnostic delay is critically reviewed based on current evidence, as well as their major causes, main problems, and potential improvement strategies.

Prognostic and Clinicopathological Significance of the Loss of Expression of Retinoblastoma Protein (pRb) in Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to evaluate the scientific evidence on the implications of retinoblastoma protein (pRb) alterations in oral cancer, in order to determine its prognostic and clinicopathological significance. PubMed, Embase, Web of Science, and Scopus were searched for studies published before February 2022, with no restrictions by publication date or language. The quality of the studies using the Quality in Prognosis Studies tool (QUIPS tool). Meta-analysis was conducted to achieve the proposed objectives, as well as heterogeneity, subgroup, meta-regression, and small study-effects analyses. Twenty studies that met the inclusion criteria (2451 patients) were systematically reviewed and meta-analyzed. Our results were significant for the association between the loss of pRb expression and a better overall survival (HR = 0.79, 95%CI = 0.64-0.98, p = 0.03), whereas no significant results were found for disease-free survival or clinico-pathological parameters (T/N status, clinical stage, histological grade). In conclusion, our evidence-based results demonstrate that loss of pRb function is a factor associated with improved survival in patients with OSCC. Research lines that should be developed in the future are highlighted.

Association of oral lichen planus with hepatic disorders and hepatocellular carcinoma: systematic review and meta-analysis

Background: Oral lichen planus (OLP) is a prevalent autoimmune chronic inflammatory disease of unknown etiology. The importance of the association between hepatic disease and OLP lies in the fact that many of these disorders (HC, HB, cirrhosis, hepatic steatosis) behave as risk factors for hepatocellular carcinoma. Material and methods: We searched PubMed, Embase, Web of Science, and Scopus for studies published before January 2022. We evaluated the quality of studies (Joanna Briggs Institute tool). We performed meta-analyses, investigated the heterogeneity between studies, and we also carried out subgroups, meta-regression, and small-study effects analyses. 146 studies (21,187 patients) were included in this study. Our study aims to evaluate current evidence on the prevalence and magnitude of association between hepatic diseases (especially those with risk of malignancy), hepatocellular carcinoma and OLP. Results: Our results suggest that patients with OLP present a significant tendency to the development of hepatitis B (OR=1.62, 95%CI=1.01-2.40, p=0.02), hepatitis C (OR=4.09, 95%CI=2.77-6.03, p<0.001), cirrhosis (OR=5.58, 95%CI=1.83-16.96, p=0.002), hepatic steatosis (OR=5.71, 95%CI=0.97-33.60, p=0.05) and hepatocellular carcinoma (OR=3.10,95%CI=1.14-8.43, p=0.03). Conclusions: Patients with OLP should be investigated to rule out the presence of hepatic disease, which can lead to hepatocellular carcinoma, allowing an early diagnosis that would help to a better approach to liver disease and a notable improvement in prognosis in terms of both progression and severity. (AU)

Autoimmune disorders in oral lichen planus: A systematic review and meta-analysis.

OBJECTIVES: The association of OLP with other autoimmune processes points to the possibility that OLP-affected patients are actually developing an autoimmune status that predisposes them to autoaggression against different targets. This systematic review and meta-analysis aim to evaluate the current evidence on the prevalence of autoimmune disorders in patients with OLP and their magnitude of association. METHODS: We searched PubMed, Embase, Web of Science, Scopus databases for the studies published before May 2021, with no limitation in regards to their publication date or language. We evaluated the quality of studies, carried out meta-analyses and performed heterogeneity, subgroups, meta-regression, and small-study effects analyses. RESULTS: Inclusion criteria were met by 153 studies (23,327 patients). Our results indicate the existence of high prevalence and a frequent association between OLP and some autoimmune disorders, especially in regards to thyroid disease (PP = 7.96%, 95% CI = 6.32-9.75; OR = 1.99, 95% CI = 1.60-2.49, p < 0.001) and diabetes mellitus (PP = 9.41%,95% CI = 8.16-10.74; OR = 1.64, 95% CI = 1.34-2.00, p < 0.001). CONCLUSIONS: Our study demonstrates the existence of a comorbidity between autoimmune thyroid diseases as well as between diabetes mellitus and OLP respectively. Quality of evidence should be upgraded on other autoimmune diseases (fibromyalgia, gastrointestinal disorders, rheumatic diseases, Sjogren's syndrome, lupus erythematosus, and dermatological diseases) for which the current data do not allow us to know whether they are really associated with OLP.

Oral lichen planus and related lesions. What should we accept based on the available evidence?

Recent new terminologies have been proposed for lesions in the sphere of oral lichen planus (OLP) that theoretically present unique aetiological, clinical, prognostic or management characteristics different from those of the so-called typical forms of OLP. We aimed to critically analyse what concepts and terminologies related to OLP should we accept based on the available evidence. A review of the literature was carried out in order to critically analyse the concepts and terminologies related to OLP. New concepts and terminologies include oral lichenoid lesions; contact lichenoid reactions, drug lichenoid reactions or those in the context of graft-versus-host disease; chronic ulcerative stomatitis; lichen planus pemphigoid; and some lesions that are difficult to categorise, such as OLP with features of proliferative verrucous leukoplakia and lichenoid lesions of the upper labial mucosa. A multidisciplinary, multicontinent working group has recently published a guideline with recommendations for modifying definitions and terminologies associated with a disease, among which a reasoned, evidence-based justification for the proposed change is considered essential. An in-depth analysis of the newly proposed terms for OLP-related lesions shows that many of them are not justified. In this paper, we set out our position on the basis of the existing evidence on the appropriateness of the use of these new terms.

Hallmarks of Cancer Expression in Oral Lichen Planus: A Scoping Review of Systematic Reviews and Meta-Analyses.

Oral lichen planus (OLP) is a common chronic inflammatory disease of unknown etiology and likely autoimmune nature that is currently considered an oral potentially malignant disorder, implying that patients suffering from this process are at risk of developing oral cancer in their lifetime. The molecular alterations that develop in OLP and that make the affected oral epithelium predisposed to malignancy are unknown, although, as in other autoimmune diseases (ulcerative colitis, primary biliary cirrhosis, etc.), they may be linked to oncogenesis-promoting effects mediated by the inflammatory infiltrate. So far there is no in-depth knowledge on how these hallmarks of cancer are established in the cells of the oral epithelium affected by OLP. In this scoping review of systematic reviews and meta-analyses the state of evidence based knowledge in this field is presented, to point out gaps of evidence and to indicate future lines of research. MEDLINE, Embase, Cochrane Library and Dare were searched for secondary-level studies published before October 2022. The results identified 20 systematic reviews and meta-analyses critically appraising the hallmarks tumor-promoting inflammation (n = 17, 85%), sustaining proliferative signaling (n = 2, 10%), and evading growth suppressors (n = 1, 5%). No evidence was found for the other hallmarks of cancer in OLP. In conclusion, OLP malignization hypothetically derives from the aggressions of the inflammatory infiltrate and a particular type of epithelial response based on increased epithelial proliferation, evasion of growth-suppressive signals and lack of apoptosis. Future evidence-based research is required to support this hypothesis.

Challenges in the Early Diagnosis of Oral Cancer, Evidence Gaps and Strategies for Improvement: A Scoping Review of Systematic Reviews.

Oral cancer is a growing problem, accounting for 377,713 worldwide new cases per year, and 177,757 deaths annually and representing a 5-year mortality rate close to 50%, which is a considerable mortality that has not decreased substantially in the last 40 years. The main cause of this high mortality is related to the diagnosis of a high percentage of oral cancers in advanced stages (stages III and IV) in which treatment is complex, mutilating or disabling, and ineffective. The essential cause of a cancer diagnosis at a late stage is the delay in diagnosis, therefore, the achievement of the objective of improving the prognosis of oral cancer involves reducing the delay in its diagnosis. The reasons for the delay in the diagnosis of oral cancer are complex and involve several actors and circumstances-patients, health care providers, and health services. In this paper, we present the results of a scoping review of systematic reviews on the diagnostic delay in oral cancer with the aim to better understand, based on the evidence, and discuss in depth, the reasons for this fact, and to identify evidence gaps and formulate strategies for improvement.

Prognostic and Clinicopathological Significance of Telomerase Reverse Transcriptase Upregulation in Oral Cancer: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis was to evaluate the current evidence on the prognostic and clinicopathological significance value of telomerase reverse transcriptase (TERT) upregulation in patients with oral squamous cell carcinoma (OSCC). PubMed, Embase, Web of Science, and Scopus were searched for studies published before April 2022, not restricted by date or publication language. The methodological quality of primary-level studies was critically assessed using the Quality in Prognosis Studies (QUIPS) tool. We carried out meta-analyses, explored heterogeneity and its sources, and performed subgroup, meta-regression, sensitivity, and small-study effects analyses. Twenty-one studies (1698 patients) met inclusion criteria. TERT protein overexpression was significantly associated with worse overall survival (hazard ratio [HR] = 3.01, 95% CI = 1.70−5.35, p < 0.001), disease-free survival (HR = 4.03, 95% CI = 1.80−9.05, p = 0.001), and higher histological grade OSCC (odds ratio [OR] = 3.20, 95% CI = 1.83−5.62, p < 0.001). These large effect sizes were consistently obtained by homogeneous subgroups (p > 0.10, I2 = 0.0, respectively), which reflects a high quality of evidence. On the other hand, TERT gene mutations obtained constantly nonsignificant null effect sizes for all outcomes investigated, evidencing no prognostic or clinicopathological value. In conclusion, our findings indicate that TERT upregulation is a prognostic indicator of poor survival in oral cancer. Our findings support the immunohistochemical assessment of TERT overexpression, which could probably be incorporated into the prognostic evaluation of OSCC.

Hallmarks of Cancer Applied to Oral and Oropharyngeal Carcinogenesis: A Scoping Review of the Evidence Gaps Found in Published Systematic Reviews.

In 2000 and 2011, Hanahan and Weinberg published two papers in which they defined the characteristics that cells must fulfil in order to be considered neoplastic cells in all types of tumours that affect humans, which the authors called "hallmarks of cancer". These papers have represented a milestone in our understanding of the biology of many types of cancers and have made it possible to reach high levels of scientific evidence in relation to the prognostic impact that these hallmarks have on different tumour types. However, to date, there is no study that globally analyses evidence-based knowledge on the importance of these hallmarks in oral and oropharyngeal squamous cell carcinomas. For this reason, we set out to conduct this scoping review of systematic reviews with the aim of detecting evidence gaps in relation to the relevance of the cancer hallmarks proposed by Hanahan and Weinberg in oral and oropharyngeal cancer, and oral potentially malignant disorders, and to point out future lines of research in this field.

Significance of p53 overexpression in the prediction of the malignant transformation risk of oral potentially malignant disorders: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the current evidence in relation to the predictive value of p53 overexpression as a biomarker of the malignant transformation risk in oral potentially malignant disorders (OPMD). MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science and Scopus for studies published before July-2021, not restricted by date or publication language, with longitudinal design and assessing p53 overexpression by immunohistochemistry. We evaluated the quality of primary-level studies using QUIPS tool. We carried out meta-analyses, examined inter-study heterogeneity through subgroup and meta-regression analyses, and performed sensitivity and small-study effects analyses to test the stability and reliability of results. RESULTS: Twenty four studies (1,210 patients) met inclusion criteria. P53 overexpression was associated with a statistically significant about 2 fold risk (RR = 1.88, 95 %CI = 1.39-2.56, p < 0.001). Leukoplakia maintained this significant relationship after subgroup meta-analysis (p = 0.002). Regarding the immunohistochemical technique, better results were obtained by the subgroups using anti-p53 DO7 antibody (p = 0.001), at high concentration (dilution < 1: 100, p < 0.001), incubated for long periods (overnight, p = 0.02), and at low temperature (4 °C, p = 0.007). Furthermore, meta-regression analysis showed that the association between p53 overexpression and higher oral cancer risk was independent of the presence and/or severity of epithelial dysplasia (p > 0.05). CONCLUSION: Our systematic review and meta-analysis supports the assessment of p53 overexpression in the prediction of the malignant transformation risk of OPMD.

Depression, anxiety, and stress in oral lichen planus: a systematic review and meta-analysis.

OBJECTIVES: We present this systematic review and meta-analyses to evaluate current evidence on the prevalence of depression, anxiety, and stress in patients with oral lichen planus and their magnitude of association. MATERIAL AND METHODS: We searched PubMed, Embase, Web of Science, Scopus, PsycInfo, and Google Scholar for studies published before January 2021. We evaluated the quality of studies using a specific method for systematic reviews addressing prevalence questions, designed by the Joanna Briggs Institute. We carried out meta-analyses and performed heterogeneity, subgroups, meta-regression, and small-study effects analyses. RESULTS: Fifty-one studies (which recruited 6,815 patients) met the inclusion criteria. Our results reveal a high prevalence of depression (31.19%), anxiety (54.76%), and stress (41.10%) in oral lichen planus. Furthermore, OLP patients presented a significantly higher relative frequency than control group without OLP for depression (OR = 6.15, 95% CI = 2.73-13.89, p < 0.001), anxiety (OR = 3.51, 95% CI = 2.10-5.85, p < 0.001), and stress (OR = 3.64, 95% CI = 1.48-8.94, p = 0.005), showing large effect sizes. Subgroups meta-analyses showed the relevance of the participation of psychologists and psychiatrists in the diagnosis of depression, anxiety, and stress in patients with OLP. Multivariable meta-regression analysis showed the importance of the comorbidity of depression-anxiety in patients with OLP. CONCLUSIONS: Our systematic review and meta-analysis show that patients with OLP suffer a higher prevalence of depression, anxiety, and stress, being more frequent than in general population. Clinical relevance In the dental clinic, especially dentists should be aware of depression, anxiety, and stress in OLP patients to achieve a correct referral.

Immunohistochemical analysis of epithelium adjacent to lip cancer: A meta-analysis.

OBJECTIVES: To identify the immunohistochemical pattern of non-tumoral epithelium adjacent to lip cancer (ANTE) to unveil molecular alterations and potential biomarkers in lip cancer patients. MATERIALS AND METHODS: A systematic search at MEDLINE, EMBASE and proceedings Web of Science, OpenGrey and WorldCat. The PICOS outline (Population: lip cancer patients; Intervention: immunostaining with biomarkers in surgical specimens; Comparisons: ANTE versus LC; Outcomes: primary-to identify the immunohistochemical pattern of peritumoral epithelium and secondary-to assess the immunoreactivity of LC epithelium; and Study design: cross-sectional, case-control and cohort studies). RESULTS: A total of 339 records were identified. Seven studies reporting on ANTE and LCs were included in the qualitative synthesis, and 4 of them (p53 immunostaining) were selected for meta-analysis. In the ANTE group, the pooled prevalence of p53 was 0.74 (95% CI: 0.66 - 0.82), while in the lip squamous cell carcinoma group this prevalence was 0.83 (95% CI: 0.75 - 0.89). CONCLUSIONS: Similar immunoexpression was found in lip epithelium adjacent to lip carcinoma, even in epithelia with normal appearance or mild histological alterations. The role of biomarkers in the follow-up of actinic cheilitis patients deserves additional clinical assessment.

State of Evidence on Oral Health Problems in Diabetic Patients: A Critical Review of the Literature.

Diabetes mellitus (DM) is a global health problem, having recognized that in the next 20 years the number of diabetic patients in the world will increase to 642 million. DM exerts enormous repercussions on general health diabetic (especially derived from vascular, cardiac, renal, ocular, or neurological affectation). It entails in addition a high number of deaths directly related to the disease, as well as a high health care cost, estimated at $673 billion annually. Oral cavity is found among all the organs and systems affected in the course of DM. Important pathologies are developed with higher prevalence, such as periodontitis (PD), alterations in salivary flow, fungal infections, oral cancer, and oral potentially malignant disorders (OPMD). It has been proven that PD hinders the metabolic control of DM and that the presence of PD increases the possibility for developing diabetes. Despite the relevance of these oral pathologies, the knowledge of primary care physicians and diabetes specialists about the importance of oral health in diabetics, as well as the knowledge of dentists about the importance of DM for oral health of patients is scarce or non-existent. It is accepted that the correct management of diabetic patients requires interdisciplinary teams, including dentists. In this critical review, the existing knowledge and evidence-degree on the preventive, clinical, diagnosis, prognosis, and therapeutic aspects of oral diseases that occur with a significant frequency in the diabetic population are developed in extension.

Prognosis Parameters of Oral Carcinomas Developed in Proliferative Verrucous Leukoplakia: A Systematic Review and Meta-Analysis.

Proliferative verrucous leukoplakia (PVL) is contemplated by the World Health Organization (WHO) as an oral potentially malignant disorder (OPMD) with a high the highest malignant transformation ratio among all OPMD (approximately 50%). Our aim was to evaluate the current evidence in relation to the prognosis of oral carcinoma developed in patients with proliferative verrucous leukoplakia (PVL-OC). We searched PubMed, Embase, Web of Science and Scopus for published studies (upper date limit = June 2021). We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses, examined inter-study heterogeneity through subgroup and meta-regression analyses, and performed sensitivity and small-study effects analyses to test the stability and reliability of results. 23 studies met inclusion criteria (505 patients with PVL, of which 288 developed a total of 504 carcinomas). The meta-analyzed overall mortality rate was 21.29% (pooled proportions [PP] = 95% confidence intervals [CI] = 8.77-36.36) for PVL-OC, clearly lower than the 34.7-50% mortality rate for conventional oral cancer reported in previous studies. In comparison with a single study reporting on conventional oral cancers, mortality was significantly lower for PVL-OC (hazard ratio = 0.29 [95%CI = 0.10-0.89], p = 0.03). Univariable meta-regression verified that case series that presented higher proportions of verrucous carcinomas showed a better survival of PVL-OC (p = 0.05), but not with higher proportion of oral squamous cell carcinomas (p = 0.74). Significant differences were not found for other relevant variables such as follow up period (p = 0.44) or multiple tumor development (p = 0.74). In conclusion, PVL-OC show favorable prognostic parameters, especially with regard to the mortality rate.