Transformation Of Oral Lichen Planus Research Articles

A Molecular Hypothesis on Malignant Transformation of Oral Lichen Planus: A Systematic Review and Meta-Analysis of Cancer Hallmarks Expression in This Oral Potentially Malignant Disorder.

We aimed to qualitatively and quantitatively analyze, through a systematic review and meta-analysis, the current evidence on the differential expression of the hallmarks of cancer in oral lichen planus (OLP) samples, in order to know the earliest molecular mechanisms that could be involved in the malignant transformation of this oral potentially malignant disorder. We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2023. We evaluated the methodological quality of studies and carried out meta-analyses to fulfill our objectives. Inclusion criteria were met by 110 primary-level studies, with 7065 OLP samples, in which the expression of 104 biomarkers were analyzed through immunohistochemistry. Most OLP samples showed sustained cell proliferation signaling (65.48%, 95%CI = 51.87-78.02), anti-apoptotic pathways (55.93%, 95%CI = 35.99-75.0), genome instability (48.44%, 95%CI = 13.54-84.19), and tumor-promoting inflammation events (83.10%, 95%CI = 73.93-90.74). Concurrently, OLP samples also harbored tumor growth suppressor mechanisms (64.00%, 95%CI = 53.27-74.12). In conclusion, current evidence indicates that molecular mechanisms promoting hyperproliferative signaling, an antiapoptotic state with genomic instability, and an escape of epithelial cells from immune destruction, are developed in LP-affected oral mucosa. It is plausible that these events are due to the actions exerted by the chronic inflammatory infiltrate. Malignant transformation appears to be prevented by tumor suppressor genes, which showed consistent upregulation in OLP samples.

Malignant Transformation in Oral Lichen Planus and Lichenoid Reactions in Southern Thai Population

Objectives: This study aimed to determine the prevalence of malignant transformation (MT) and the incidence rate of oral squamous cell carcinoma (OSCC) in oral lichen planus (OLP) and oral lichenoid reaction (OLR) patients from southern Thailand. Methods: This hospital-based retrospective cohort study comprised OLP/OLR patients who were treated between January 2016 and December 2022. Data on the general characteristics, clinical manifestations and laboratory investigations were obtained from the hospital records and analyzed. Descriptive and analytical statistics were performed to assess the demographic data, clinical profiles of the patients and the prevalence and incidence rate of MT. Results: A total of 117 patients were included in the study; 103 (88%) were diagnosed with OLP, and 14 (12%) were diagnosed with OLR. The median follow-up time was 15.6 months (interquartile range; 6.1-46.0). The overall prevalence of MT in OLP/OLR was 1.71% (2/117 patients); specifically, MT in OLP was 1.94% (2/103 patients). The overall annual incidence rate of MT into OSCC was 0.0060 (95% confidence interval, 0.0015-0.0240). Conclusions: These findings suggest that OLP is a potentially malignant disorder with an MT incidence of 1.94% in the southern Thai population. OLP patients must be regularly followed-up and advised about the risk of MT.

Characteristics of Clinically Classified Oral Lichen Planus in Optical Coherence Tomography: A Descriptive Case-Series Study.

Malignant transformation of oral lichen planus (OLP) into oral squamous cell carcinoma is considered as one of the most serious complications of OLP. For the early detection of oral cancer in OLP follow-up, accurate localization of the OLP center is still difficult but often required for confirmatory biopsy with histopathological examination. Optical coherence tomography (OCT) offers the potential for more reliable biopsy sampling in the oral cavity as it is capable of non-invasively imaging the degenerated oral layer structure. In this case-series study with 15 patients, features of clinically classified forms of OLP in OCT cross-sections were registered and correlated with available histologic sections. Besides patients with reticular, atrophic, erosive and plaque-like OLP, two patients with leukoplakia were included for differentiation. The results show that OCT yields information about the epithelial surface, thickness and reflectivity, as well as the identifiability of the basement membrane and the vessel network, which could be used to complement the visual clinical appearance of OLP variants and allow a more accurate localization of the OLP center. This forms the basis for further studies on OCT-assisted non-invasive clinical classification of OLP, with the aim of enabling decision support for biopsy sampling in the future.

Risk of Oral Squamous Cell Carcinoma in One Hundred Patients with Oral Lichen Planus: A Follow-Up Study of Umberto I University Hospital of Rome.

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department's database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793-63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182-16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464-138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661-31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors.

CD44 Expression in Oral Lichen Planus and Related Lesions-An Immunohistochemical Study.

Cluster of differentiation 44 (CD44) is a cell surface adhesion protein involved in the progression and metastasis of oral squamous cell carcinoma. The current study aims to evaluate the expression of CD44 in oral lichen planus and related lesions and thereby assess the relative risk of malignant transformation of these lesions. Formalin-fixed paraffin-embedded tissue blocks of 10 oral lichen planus (Group 1), 10 oral lichenoid lesions (Group 2), 8 with oral lichen planus with dysplasia (Group 3), and 5 with lichenoid dysplasia (Group 4) were included in the study. Immunostaining was done for the tissue sections using CD44 mouse monoclonal antibody. Staining density, staining intensity, and immunoreactive scores of CD44 were evaluated in all four groups. Statistical analysis was done by Statistical Package for the Social Sciences® software and the Kruskal-Wallis test was used. CD44 staining pattern of lichenoid dysplasia and lichen planus with dysplasia changed from membranous to cytoplasmic. The membranous CD44 immunoreactivity was mild with a score of 2.25 for Group 3 and 1.6 for Group 4 whereas moderate for other groups with a P-value of 0.009. The cytoplasmic immunoreactivity was significantly high in Group 3 (5.3 ± 2.6) followed by Group 4 (3.2 ± 1.2), Group 2 (1 ± 1.8), and Group 1 (0.7 ± 1.3) with a P-value of 0.001. The CD44 membranous immunoreactivity scores were low while the cytoplasmic immunoreactivity was high in oral lichen planus with dysplasia and oral lichenoid dysplasia when compared to oral lichen planus and oral lichenoid lesions. CD44 immunostaining pattern can help in assessing the malignant transformation of oral lichen planus or lichenoid lesions.

Malignant transformation of oral lichen planus during COVID-19 crisis.

Malignant transformation of oral lichen planus during COVID-19 crisis.

Retrospective Study of Oral Lichen Planus and Oral Lichenoid Lesions: Clinical Profile and Malignant Transformation.

Oral lichen planus (OLP) and other oral lichenoid lesions (OLL) are reported to have the potential of malignant transformation and dysplastic changes, turning into oral squamous cell carcinoma (SCC). While the world health organization (WHO) has classified OLP as a precancerous lesion of the oral cavity, there is still much debate among researchers about its risks and malignancy potential. The present study aimed to determine malignant transformation in OLP and OLL and understand related risk factors. This retrospective study was performed on 356 patients of the Oral Medicine Department of Dental School of Kerman Medical University from 1998 to 2020. All patients' records were gathered. In addition, patients were followed up routinely. Second biopsy was taken as needed. The samples, previously taken from the patients, were re-evaluated according to WHO histopathologic criteria for diagnosing OLP, OLL, dysplasia, and SCC by an experienced pathologist and compared with first reports. Dysplastic changes were observed in 6.2% of the patients. In more than half of the patients, dysplastic changes were present right from the start and 2.20% of the patients had experienced dysplastic changes averagely within 2.05 years of the onset of lesions. Multiple logistic regression showed that the risk of dysplasia increases with aging (p= 0.013), smoking (p= 0.0001), and thyroid disorders (p= 0.008). Given the rather high prevalence of oral lichen planus and lichenoid lesions, further research appears to be needed to determine the etiology of these lesions, malignant transformations, and the factors affecting this probability. Considering the findings, it is imperative to meticulously record the information of all patients with oral lichen planus and lichenoid lesions in the initial examinations as well as close follow-ups and employ diagnostic tools such as toluidine blue staining or even repeat biopsy when necessary.

P53 Polymorphism in Oral Lichen Planus

Oral lichen planus (OLP) is a chronic relapsing inflammatory disease. It involves T-lymphocyte aggression targeted to the basal layer of the oral mucosa.p53 plays a central role in the prevention of normal cells from the development of the malignant phenotype. Somatic alterations in p53 cause defects in normal p53 function. Wild type p53 plays an important role in repairable damage of the cell due to cellular stresses. Over-expression, as well as polymorphic variants of Mouse double minute 2(MDM2), have effects on p53 disturbances. In addition, degradation of p53 by E6 protein of high-risk human papillomavirus is also suggested as one of the mechanisms which attenuate p53 responses in oral carcinogenesis. Polymorphisms in p53 are anticipated to cause measurable disturbance in p53 function. Polymorphism of the codon 72 on exon 4 of the gene p53 is the first and most commonly known polymorphism of this gene. The presence of p53 has been demonstrated as an early marker of dysplasia in Oral Potentially Malignant Disorders. This review discusses about p53 polymorphism as an early indicator of genetic predisposition to neoplastic transformation in OLP.

Diagnostic and Prognostic Value of miR-4789-5p, miR-3941, circ_0045638 and circ_0045639 in Malignant Transformation of Oral Lichen Planus and OSCC

Diagnostic and Prognostic Value of miR-4789-5p, miR-3941, circ_0045638 and circ_0045639 in Malignant Transformation of Oral Lichen Planus and OSCC

THE PROPORTION OF ORAL LICHEN PLANUS CASES WITH MALIGNANT TRANSFORMATION MAY BE HIGHER, THAN REPORTED TO DATE.

González-Moles MÁ, Ramos-García P, Warnakulasuriya S. An appraisal of highest quality studies reporting malignant transformation of oral lichen planus based on a systematic review. Oral Dis. 2021 Nov;27(8):1908-1918. doi: 10.1111/odi.13741. Epub 2020 Dec 24. PMID: 33274561. The Royal College of Physicians and Surgeons (RCPSG) provided logistic support for holding the expert symposium. Henry Schein Cares provided an educational grant for travel expenses for some of the invited experts. Systematic review with meta-analysis.

Malignant Transformation of Oral Lichen Planus: A Case Report and Review of Literature

Oral lichen planus (OLP) is a relatively common inflammatory mucocutaneous disease with unknown etiology. The disease affects 0.5 to 2% of the general population with a predilection for females and middle-aged adults. It commonly presents as bilateral symmetrical lesions on the buccal mucosa, dorsal tongue, and gingiva. The two most common subtypes are reticular and erosive forms. According to Gonzales-Moles, the overall malignant transformation rate is 1.1%, with the reported range of 0% to 12.5%. Here, we present a case of OLP transformed into oral squamous cell carcinoma (OSCC). Case: A 58-year-old woman presented with a 19-year history of leukoplakia on the dorsal and ventral tongue and a 9-year history of painful and eroded gums. In 2002, she had a diagnosis of lichen planus with low-grade dysplasia on biopsy. An incisional biopsy of the lesions from the right mandibular buccal gingiva and right dorsal tongue was performed in 2010. The diagnosis was OLP of gingiva and benign verrucous keratosis of the dorsal tongue. The oral lesions were treated and regularly followed up for 2.5 years, and the patient was lost to follow-up for seven years. In 2019, she presented with biopsy-proven invasive poorly differentiated OSCC of the right mandibular gingiva. She underwent a right marginal mandibulectomy, right selective neck dissection, local flap, and teeth extraction. On an 8-month-follow-up, the patient developed a palpable nodule at the base of the right neck, and a level 1 neck node biopsy was positive for metastatic SCC. She had modified radical neck dissection and right mandibular vestibuloplasty. The patient is currently undergoing radiation therapy. The severity and progression of this case highlight the malignant potential of lichen planus and the importance of careful follow-up.

What is the malignant transformation potential of oral lichen planus?

Data sources In this systematic review and meta-analysis, Medline, Scopus and Web of Science databases were searched using Medical Subject Headings (MeSH) to identify studies assessing the risk of malignant transformation in oral lichen planus (OLP).Study selection Observational studies published in English between 2003-2020 were independently assessed for inclusion by two blinded investigators.Data extraction and synthesis Data were extracted independently by two investigators followed by discussion to reach consensus. This included: study design and patient characteristics; length of follow-up; risk of bias; method of OLP diagnosis; oral squamous cell carcinoma (OSCC) risk factors; rate of malignant transformation; and individual characteristics of malignant transformation cases. Cases of malignant transformation in the included studies were only included in meta-analysis if: 1) OLP diagnosis met current diagnostic criteria; 2) OSCC developed in the same site as previously diagnosed OLP after at least six months' follow-up; 3) the patient had no history of systemic immunosuppressive therapy, head and neck malignancy, or organ transplantation. Risk of bias was assessed using the modified Newcastle-Ottawa scale, and meta-analysis was conducted to estimate overall risk of OLP malignant transformation using the DerSimonian and Laird method. Pooled univariate odds ratios (OR) for malignant transformation were calculated based on gender, smoking status, alcohol consumption, hepatitis C infection and OLP subtype.Results In total, 593 studies were identified after removal of duplicates and 33 studies were included for data extraction. The included sample comprised 12,838 patients with OLP, and 151 malignant transformation cases were reported in the included studies. The authors excluded 56 malignant transformation cases from the meta-analysis, most commonly because of the absence of pathological OLP diagnosis. Among included malignant transformation cases, the mean (SD) age was 58.1 (12.4) years, and 64% of the sample was female. Random-effects meta-analysis estimated an OLP malignant transformation rate of 0.2% (95%CI: 0.1-0.3%). Heterogeneity was low (I2 = 28.74%, p = 0.065). Malignant transformation was significantly higher among smokers (OR = 4.62, p = 0.001), alcohol consumers (OR = 3.22, p = 0.05), those with hepatitis C (OR = 3.77, p = 0.03) and atrophic or erosive OLP subtypes (OR = 2.70, p = 0.03). Gender was not associated with increased risk of malignant transformation.Conclusions The malignant transformation rate of OLP is likely to be lower than previously reported, possibly as a result of variable diagnostic criteria. Whilst encouraging, clinical vigilance remains necessary, as OLP does carry a small risk of malignant transformation. Smoking, alcohol use, hepatitis C infection and erosive or atrophic subtypes appear to have a greater rate of malignant transformation.

A Survey of Brazilian Patients with Oral Lichen Planus Showing No Evidence of Malignancy.

Objectives There is conflicting evidence as to whether oral lichen planus (OLP) can undergo malignant transformation into oral squamous cell carcinoma (OSCC). This study aimed to address this issue by analyzing a sample of Brazilian patients with either OLP or OSCC. Patients and Methods. This study was conducted in São Paulo, the world's fourth-largest city by population. Two groups of patients were analyzed. The OLP group consisted of 370 patients, while the OSCC group consisted of 154 patients. The OLP patients were followed up for up to 21 years to monitor clinical benefits from the management or changes in the lesion morphology; conversely, patients with OSCC were examined only twice for diagnostic purposes and referred to a specialized center. Data concerning systemic diseases, use of medications, type of oral lesions, and health-risk behaviors were recorded for patients in both groups. Results None of the patients with OLP developed OSCC at the lesion site. Only one female patient with erosive OLP developed OSCC in the normal, lesion-free oral mucosa. None of the OSCC patients had concomitant OLP lesions; however, a higher percentage of OSCC cases (17.5%) showed white plaques (most likely oral leukoplakia) as a precursor lesion. Conclusion The findings strongly suggest that malignant transformation of OLP is virtually nonexistent in the Brazilian population.

Whole-exome sequencing of transforming oral lichen planus reveals mutations in DNA damage repair and apoptosis pathway genes.

Oral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus-derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation. Using rigorous diagnostic criteria, we retrospectively identified patients with non-transforming oral lichen planus (i.e., known to be non-transforming with 5years of clinical follow-up; n=17), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, n=9), or oral squamous cell carcinoma arising in lichen planus (n=17). Gene mutational profiles derived from whole-exome sequencing on fixed mucosal specimens were compared among the groups. The four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12/17 (71%) of oral squamous cell carcinomas and 5/9 (56%) of transforming oral lichen planus but were absent in non-transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus-associated oral squamous cell carcinomas. These findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus-related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non-transforming oral lichen planus.

Significance of immunohistochemistry biomarkers in prediction of malignant transformation of oral lichen planus: A systematic review.

Background Oral lichen planus (OLP) is a chronic inflammatory disorder with increased risk for malignant transformation. Biomarker validation is a pivotal step in moving newly discovered biomarkers towards clinical implementation. We performed a systematic review of studies on biomarkers related to OLP, wherein biomarkers have been described in at least two independent studies. Our aim was to determine whether any of these biomarkers might be promising in predicting the increased risk of malignant transformation of OLP.Material and Methods We searched the following databases until August 2021: PUBMED, EMBASE, and Web of Science. Due to high heterogeneity, a qualitative rather than quantitative assessment was conducted. Only proteins that consistently showed a significantly high level of expression in neoplastic tissues versus OLP in two or more publications were considered as promising markers.Results Initial database researches identified 1671, of which 24 articles were included in the final analysis. The most frequently reported proteins were p53, Bcl-2 and Ki-67, though there were controversies. PCNA and P21 were the only proteins that showed consistent evidence of clinical usefulness as cancer predictors to be considered as promising markers. Extensive methodological variations in the evaluation of expressions and statistical analyses of the included markers were observed, which hampered comparisons of the results.Conclusions Multiple levels of heterogeneity with a scarcity of high-quality studies were identified. PCNA and P21 were identified as promising predictive markers for evaluating the risk of malignant transformation of OLP, but they require further validation. The focus of future research on validation of predictive biomarkers of OLP should be considered as a high priority because it will accelerate the introduction of newly discovered markers into the clinical setting. Key words:Oral lichen planus, Immunohistochemistry, biomarkers, malignant transformation, PCNA, P21, p53, BCl-2.

Evaluation of the Potential of Malignant Transformation in Oral Lichen Planus by Immunohistochemistry

Evaluation of the Potential of Malignant Transformation in Oral Lichen Planus by Immunohistochemistry

Risk co-factors inducing malignant transformation of oral lichen planus: A literature review of clinical studies

Oral lichen planus (OLP) is an autoimmune chronic inflammatory disease. The potential risk of malignant transformation in OLP remains controversial. The aim of the present study was to review original clinical studies published in indexed databases, which assessed the potential risk cofactors which were implicated in the malignant transformation of oral lichen planus. We focused our search to include most of the studies that reported malignant transformation of oral lichen planus using different combinations of the following key indexing terms: oral lichen planus, malignant transformation, smoking, alcohol, chronic inflammation, candida, human papillomavirus (HPV), hepatitis C virus (HCV) and immunosuppression. The animal studies were excluded from our study. Despite a dearth of studies on this topic we have identified consumption of tobacco and/or alcohol, the presence of erosive and/or atrophic areas, infection with candida, HCV, HPV, and immunosuppression as significant cofactors. Patients with OLP with these risk co-factors are at risk of malignant transformation should, therefore be followed up for an extensive period or even for life.

Malignant transformation of oral lichen planus: a retrospective study of 565 Japanese patients

BackgroundOral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear.MethodsWe designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded.ResultsThe study population included 123 men and 442 women aged 21–93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type.ConclusionsOur results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.

Role of Human Papilloma Virus in Malignant Transformation of Oral Lichen Planus: A Systematic Review.

Lichen planus (LP) is a chronic inflammatory mucocutaneous disease. The disease has a cell-mediated immune reaction which is precipitated by a specific trigger which turns the self-peptides antigenic. The role of human papillomavirus (HPV) in the malignant transformation of oral LP (OLP) has always been debated. Establishing a definitive part played by HPV in the malignant transformation of OLP, would possibly provide screening for the viruses, HPV vaccination, and antiviral therapy along with conventional treatment in LP which could improve prognosis. This systematic review is to assess the role of HPV in the malignant transformation of OLP. We performed a systematic search of PubMed, MEDLINE, and Google. The information was extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All full-text papers that assessed the association of HPV in malignant transformation of OLP were considered eligible. The outcome parameter included the malignant transformation of OLP. We found a total of 19 studies from which five were found suitable for the review. Results from this systematic review showed HPV is associated with OLP. There is an increased prevalence of HPV in the erosive-atrophic (EA) variant of OLP compared to non-EA variant. There seems to be no strong evidence to prove the association between HPV and malignant transformation of OLP. Taking up the oncogenic potential of high-risk types and OLP as a potentially malignant disorder, more number of studies need to be performed on the dysplastic subtype of OLP and in those OLP lesions that progress to oral squamous cell carcinomas.

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

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. 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. 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). 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.