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.

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.

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.

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.

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.

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.

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.

Assembling a consensus on actinic cheilitis: A Delphi study.

AIMS: To discuss the terminology to define and classify actinic cheilitis (AC) and to build a consensus on the diagnostic and therapeutic approaches to AC. METHODS: Two-round Delphi study using a questionnaire including 34 closed sentences (9 on terminology and taxonomy, 5 on potential for malignant transformation, 12 on diagnostic aspects, 8 on treatment) and 8 open questions. Experts' agreement was rated using a Likert scale (1-7). RESULTS: A consensus was reached on 24 out 34 statements (73.5%) and on 5 out of 8 (62.5%) close-ended questions. The response rate was identical in both rounds (attrition of 0%). AC is the term with the highest agreement (median of 7 (strongly agree; IQR: 6-7)) and the lowest dispersion (VC = 21.33). 'Potentially malignant disorder' was the preferred classification group for AC (median of 7) and 85.6% of participants showing some level of agreement (CV < 50). Experts (66.75%) consider AC a clinical term (median: 7; IQR: 4-7) and believe definitive diagnosis can be made clinically (median: 6; IQR: 5-7), particularly by inspection and palpation (median: 5; IQR: 4-6). Histopathological confirmation is mandatory for the management of AC (median: 5; IQR: 2.5-7), even for homogeneous lesions (median: 5; IQR: 3.5-6). Consensus was reached on all treatment statements (VC < 50). CONCLUSIONS: AC is a potentially malignant disorder with a significant lack of agreement on diagnostic criteria, procedures, biopsy indications and the importance of techniques to assist in biopsy. A consensus was reached on nomenclature and management of this disorder.

An appraisal of highest quality studies reporting malignant transformation of oral lichen planus based on a systematic review.

OBJECTIVES: We present a critical review of the papers published in the international scientific literature on malignant transformation of oral lichen planus (OLP). Our aim is to report the most realistic estimate of the proportion of OLP cases with malignant transformation based on the highest quality of evidence. MATERIALS AND METHODS: Following a literature search, we selected 89 papers that were published on this topic until November 2020. We applied to these papers an adaptation of the methodological quality criteria of the QUIPS tool and we ordered all of them according to their methodological quality. The papers that were in the upper quartile of methodological quality (10 papers) were selected and analyzed. RESULTS: The pooled proportion (expressed as percentage) of malignant transformation of OLP reported in these high methodological quality papers was 2.28% (95% confidence intervals = 1.49-3.20). CONCLUSIONS: We observe that the proportion of malignancy is higher in research carried out under strict methodological quality criteria. In this critical review, we propose criteria for conducting follow-up studies on OLP to report on malignant transformation under strict quality standards.

Oral cancer development in lichen planus and related conditions-3.0 evidence level: A systematic review of systematic reviews.

A systematic review of systematic reviews-aka overview of reviews, a novel type of study design providing a tertiary level of evidence-is presented on systematic reviews (SR) and meta-analyses (MTA) evaluating the cancer development in oral lichen planus (OLP), oral lichenoid lesions (OLL), and oral lichenoid reactions (OLR). We searched for SR-MTA published before January 2021. We evaluated the methodological quality of SR-MTA using AMSTAR2 and checked the quality of evidence. Inclusion criteria were met by seven SR-MTA. Oral cancer ratios ranged between 0.44% and 2.28% for OLP, between 1.88% and 3.80% for OLL, and 1.71% for OLR. Significant factors on cancer development reported in SR-MTA were the presence of epithelial dysplasia, the consumption of tobacco and alcohol, the infection by the hepatitis C virus, the presence of atrophic and erosive lesions, and the location on the tongue. Only, one of the SRs assessed the quality of evidence, and most of them were judged to be of critically low methodological quality. In conclusion, based on the reported evidence on cancer incidence in OLP, our results reaffirm classifying OLP as an oral potentially malignant disorder. In relation to OLLs and OLRs, larger studies are necessary to provide further scientific evidence in this regard. Future follow-up studies on OLP and related lesions should be carried out under stricter criteria that improve their quality of evidence and methodological quality.

Diabetes mellitus and oral cancer/oral potentially malignant disorders: A systematic review and meta-analysis.

The objective was to evaluate current evidence on the prevalence and risk of oral cancer and potentially malignant oral disorders among patients with diabetes mellitus. We searched PubMed, Embase, Web of Science, and Scopus for observational studies published before November 2019. We evaluated the study quality using GRADE, QUIPS, and a specific method for systematic reviews addressing prevalence questions. Meta-analyses were conducted, and heterogeneity and publication bias were examined. A total of 1,489 studies were found, 116 analyzed in full text, 52 included in qualitative synthesis and 49 meta-analyzed. Pooled prevalence (PP) of oral cancer in patients with diabetic was 0.25% (95% CI = 0.15-0.39)-250 per 100,000 patients with diabetes mellitus -with a greater chance of oral cancer among patients with diabetes mellitus (OR = 1.41 [95% CI = 1.10-1.81], p = .007). Patients with oral cancer and diabetes mellitus had a higher mortality than controls (HR = 2.09 [95%CI = 1.36-3.22], p = .001). Leukoplakia had a PP = 2.49% (95% CI = 1.14-4.29)-2,490 per 100,000 patients with diabetes mellitus -(OR = 4.34 [95% CI = 1.14-16.55], p = .03). A PP of 2.72 (95% CI = 1.64-4.02) was obtained for oral lichen planus among patients with diabetic -2,720 per 100,000 patients with diabetes mellitus (OR = 1.87 [95% CI = 1.37-2.57], p < .001). A low PP was estimated for erythroplakia (0.02%[95%CI = 0.00-0.12]-20 per 100,000 patients with diabetes mellitus. In conclusion, patients with diabetes mellitus have a higher prevalence and greater chance of oral cancer and OPMD development in comparison with non-diabetic patients. In addition, patients with oral cancer suffering from diabetes mellitus have a higher mortality compared to non-diabetic patients with oral cancer.

Malignant transformation of oral proliferative verrucous leukoplakia: A systematic review and meta-analysis.

OBJECTIVES: To investigate the available evidence on the malignant transformation (MT) of oral proliferative verrucous leukoplakia (PVL). MATERIAL AND METHODS: We searched six main electronic and three grey literature databases in a two-phase process. Cohort studies investigating MT of PVL were eligible for inclusion. The risk of bias (RoB) was assessed using a specific tool developed by the Joanna Briggs Institute. Proportion meta-analyses were performed using a random-effects model. RESULTS: Study selection resulted in the inclusion of 17 studies. The pooled proportion of MT was 43.87% (95% CI = 31.93-56.13). Females (64.02%, 95% CI = 54.87-72.75) were more affected by PVL than males (35.98%, 95% CI = 27.25-45.13). Gingiva (39.6%) and buccal mucosa (21.6%) were the most frequent PVL sites. No conclusive results were found between MT and sex or age distribution, tobacco, or alcohol consumption. Gingiva was the most common site for MT (39.9%), and the most frequent histopathological subtype was conventional squamous cell carcinoma (62.1%). Four studies were classified as low, nine as moderate, and four as high RoB. CONCLUSION: The MT pooled proportion was 43.87%. Among OPMDs, PVL has the highest risk to transform to malignancy. Development and agreement on diagnostic criteria for PVL would reduce the heterogeneity among future studies.

Clinicopathological and prognostic significance of PD-L1 in oral cancer: A preliminary retrospective immunohistochemistry study.

OBJECTIVE: To evaluate the relation between PD-L1 expression in oral cavity squamous cell carcinomas and clinicopathological features as well as survival outcomes. METHODS: A retrospective immunohistochemical study was carried out on 55 archived tumours from 55 patients. Tumours were stained for PD-L1 and scored by the proportion of tumour cells with positive membranous staining. PD-L1 scores were compared to the patient's clinicopathological characteristics for any significant associations. Kaplan-Meier curves were constructed for PD-L1 positive and negative tumours to investigate any advantage to survival. RESULTS: Positive PD-L1 staining was found in 58% of tumours and was significantly more likely in non-smokers, non-drinkers and in tongue squamous cell carcinomas. Increased PD-L1 was also associated with increased lymphocyte infiltration as well as PD-L1 staining in lymphocytes and the epithelium adjacent to tumour invasion. No survival benefit was seen from PD-L1 expression in tumour cells. CONCLUSIONS: PD-L1 expression is more common in non-smokers and non-drinkers, and its presence in the adjacent non-tumour epithelium suggests it may be involved in early oncogenesis.

Worldwide prevalence of oral lichen planus: A systematic review and meta-analysis.

The objective was to assess the global oral lichen planus prevalence. We searched PubMed, EMBASE, Web of Science, and Scopus for studies published before September 2019. We evaluated the quality of studies and carried out several meta-analyses. The global pooled prevalence was 1.01%, with a marked geographical difference (p < .001). The highest prevalence was reported from Europe (1.43%) and the lowest in India (0.49%), where tobacco-associated keratosis appears to mask oral lichen planus resulting in attenuation of its prevalence. From the age of 40 years, the prevalence increases significantly and progressively (OR = 3.43, 95% CI = 2.48-4.73, p < .001). Studies that define diagnostic criteria report a higher prevalence (1.31% vs. 0.70%, p = .03), although the application of the WHO criteria (year 1978-2007) does not increase the ability to diagnose the disease compared with other criteria (p = .11). The studies performed by oral medicine/oral pathology specialists report significantly higher prevalence (1.80%) than dentists (0.61%) and dermatologists (0.33%; p < .001). In conclusion, we propose that reliable diagnostic criteria should be defined, which should include a set of essential criteria including the presence of white reticular lesions in any location of the oral mucosa. The impact of histopathological confirmation with defined diagnostic criteria must be researched in the future, although its main use should be to determine the presence or absence of epithelial dysplasia. The necessity to improve the knowledge of oral lichen planus among dentists and dermatologists through continuing education is apparent in the results of this meta-analysis.

Oral potentially malignant disorders: A consensus report from an international seminar on nomenclature and classification, convened by the WHO Collaborating Centre for Oral Cancer.

Oral potentially malignant disorders (OPMDs) are associated with an increased risk of occurrence of cancers of the lip or oral cavity. This paper presents an updated report on the nomenclature and the classification of OPMDs, based predominantly on their clinical features, following discussions by an expert group at a workshop held by the World Health Organization (WHO) Collaborating Centre for Oral Cancer in the UK. The first workshop held in London in 2005 considered a wide spectrum of disorders under the term "potentially malignant disorders of the oral mucosa" (PMD) (now referred to as oral potentially malignant disorders: OPMD) including leukoplakia, erythroplakia, proliferative verrucous leukoplakia, oral lichen planus, oral submucous fibrosis, palatal lesions in reverse smokers, lupus erythematosus, epidermolysis bullosa, and dyskeratosis congenita. Any new evidence published in the intervening period was considered to make essential changes to the 2007 classification. In the current update, most entities were retained with minor changes to their definition. There is sufficient evidence for an increased risk of oral cancer among patients diagnosed with "oral lichenoid lesions" and among those diagnosed with oral manifestations of 'chronic graft-versus-host disease'. These have now been added to the list of OPMDs. There is, to date, insufficient evidence concerning the malignant potential of chronic hyperplastic candidosis and of oral exophytic verrucous hyperplasia to consider these conditions as OPMDs. Furthermore, due to lack of clear evidence of an OPMD in epidermolysis bullosa this was moved to the category with limited evidence. We recommend the establishment of a global research consortium to further study the natural history of OPMDs based on the classification and nomenclature proposed here. This will require multi-center longitudinal studies with uniform diagnostic criteria to improve the identification and cancer risk stratification of patients with OPMDs, link them to evidence-based interventions, with a goal to facilitate the prevention and management of lip and oral cavity cancer.

An update of knowledge on PD-L1 in head and neck cancers: Physiologic, prognostic and therapeutic perspectives.

Programmed cell death-ligand 1 (PD-L1) is a transmembrane protein that acts as a co-inhibitory factor in the immune response. Its receptor, programmed cell death protein 1 (PD-1), is found on immune cells, where binding to PD-L1 can reduce the proliferation of PD-1-positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 in immune-privileged tissue plays a crucial role in peripheral tolerance. PD-L1 can be overexpressed in various malignancies, including oral squamous cell carcinoma, where it can attenuate the host immune response to tumour cells and has been associated with a worse prognosis. Monoclonal antibody therapies targeting the PD-1:PD-L1 axis have shown initial promise, but further research is needed to identify which patients will benefit. We provide an update of knowledge on PD-L1, including its structure, function and regulation. We also review studies on the overexpression of PD-L1 in cancer, specifically oral squamous cell carcinoma, and explore its potential value as a therapeutic target.

Systemic inflammatory impact of periodontitis on cognitive impairment.

OBJECTIVES: The role in dementia of systemic inflammation derived from periodontal disease is not fully elucidated. The objective of our study was to examine the impact of inflammation on the relationship between periodontitis and cognitive impairment. METHODS: We have designed a case (n = 171) and control (n = 131) study to determine the periodontal health status, grade of cognitive impairment/dementia and systemic inflammation level, the last being measured by analysis of 29 inflammatory biomarkers using multiplex techniques. RESULTS: At the time of sampling, 11 of the 29 inflammatory biomarkers were associated with cognitive impairment in patients with more severe periodontitis. However, the inflammatory response to severe periodontitis was more reduced (lower biomarker concentrations) in cases (with cognitive impairment or dementia) than in (cognitively healthy) controls, an unexpected finding. CONCLUSIONS: Based on these results, we cannot confirm that systemic inflammation derived from periodontal disease plays a relevant role in the aetiology of cognitive impairment.

An update of knowledge on cortactin as a metastatic driver and potential therapeutic target in oral squamous cell carcinoma.

Cortactin is a protein encoded by the CTTN gene, localized on chromosome band 11q13. As a result of the amplification of this band, an important event in oral carcinogenesis, CTTN is also usually amplified, promoting the frequent overexpression of cortactin. Cortactin enhances cell migration in oral cancer, playing a key role in the regulation of filamentous actin and of protrusive structures (invadopodia and lamellipodia) on the cell membrane that are necessary for the acquisition of a migratory phenotype. We also analyze a series of emerging functions that cortactin may exert in oral cancer (cell proliferation, angiogenesis, regulation of exosomes, and interactions with the tumor microenvironment). We review its molecular structure, its most important interactions (with Src, Arp2/3 complex, and SH3-binding partners), the regulation of its functions, and its specific oncogenic role in oral cancer. We explore the mechanisms of its overexpression in cancer, mainly related to genetic amplification. We analyze the prognostic implications of the oncogenic activation of cortactin in potentially malignant disorders and in head and neck cancer, where it appears to be relevant in the development of lymph node metastasis. Finally, we discuss its usefulness as a therapeutic target and suggest future research lines.

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.