Transformation Of Oral Lichen Planus Research Articles

Reduced levels of serum vitamin B12 in symptomatic cases of oral lichen planus: A cross-sectional study

ObjectivesOral Lichen Planus (OLP) is an immune mediated disease and causes oro-mucosal burning sensation that reduces food intake and hence resulting in nutritional deficiency. The present study was done to evaluate the serum levels of vitamin B12 in patients with symptomatic OLP and establish an association between reduced B12 levels and OLP. Materials and methodSerum vitamin B12 was assessed in 60 symptomatic cases of oral lichen planus and 60 healthy age and gender matched controls. ResultsSerum vitamin B12 was significantly reduced (p value < 0) in patients with oral lichen planus when compared to healthy individuals. 43.33% of cases (26 out of 60) had B12 levels less than 187 pg/ml. ConclusionOral lichen planus causes serum vitamin B12 deficiency. Vitamin B12 is linked with normal functioning of immune and neuropsychologic system which has a role to play in etiopathogenesis and malignant transformation of oral lichen planus.

Malignant transformation in oral lichen planus and lichenoid lesions: a 14-year longitudinal retrospective cohort study of 829 patients in New Zealand

The aim of this study was to identify the rate of malignant transformation in a longitudinal cohort of patients with oral lichen planus and oral lichenoid lesion (OLP/OLL) and to assess the associations between clinicopathologic aspects and malignant transformation. Data were taken from the records of 829 patients histologically diagnosed with OLP/OLL in the years 2005 to 2018. Of the study patients, 548 (66.1%) were females and 281 (33.9%) were males. The average age at diagnosis was 57.3 years. The hyperplastic type was the most frequent (58.5%). Most patients had multiple sites of involvement, with the buccal mucosa being the most frequent site of biopsy. Oral epithelial dysplasia developed in 5 (0.6%) patients with a previous histologic diagnosis of OLP/OLL and developed oral squamous cell carcinoma (OSCC) in 23 patients (2.8%) during the follow-up period. The atrophic/ulcerative forms are 25.8 times more likely to progress to OSCC compared with the hyperplastic types (hazard ratio [HR] 25.8; P < .05). The HR increases by 5% with every year of age (HR 1.05; 95% confidence interval; P < .05). In our study, oral epithelial dysplasia developed in less than 1% of patients with OLP/OLL, and OSCC in 2.8%during the follow-up period. The atrophic/ulcerative forms are 25.8 times more likely to progress to OSCC compared with the hyperplastic types. The HR increases by 5% with every year of age.

The expression of Cathepsin L in oral lichen planus

BackgroundMalignant transformation of oral lichen planus (OLP) was reported particularly in erosive type, however, it remains inconclusive. Cathepsin L was shown to promote tumor growth and invasion in many cancers. Therefore, cathepsin L expression in erosive and non-erosive OLP compared with oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) were investigated. MethodsThirty specimens of OLP (15 cases each of erosive and non-erosive OLP), 10 cases of oral epithelial dysplasia and 10 cases of OSCC were included. Ten healthy gingiva specimens were served as controls. All specimens were stained with cathepsin L antibody using immunohistochemistry technique. ResultsCathepsin L was expressed in all OLP and OSCC cases. In oral epithelial dysplasia and healthy gingiva, the expression was found at 90% and 50% respectively. The percentage of positive cells was the highest in erosive OLP (27.26 ± 12.09%), followed by non-erosive OLP (20.85 ± 7.43%), OSCC (20.15 ± 15.70%), oral epithelial dysplasia (9.24 ± 7.00%) and healthy gingiva (2.27 ± 5.65%). Most of non-erosive OLP cases showed mild staining intensity while erosive OLP and OSCC showed moderate staining intensity. Cathepsin L was mainly expressed at basement membrane zone and inflammatory cells of OLP. In OSCC, the expression was found in tumor islands and keratin pearls. In oral epithelial dysplasia and normal gingiva, cathepsin L expressions were low and presented in scattered pattern in both epithelium and connective tissue. ConclusionAccording to the patterns of expression in this study, cathepsin L could be implicated in pathogenesis and severity of OLP.

Malignant transformation of oral lichen planus and related genetic factors

Oral lichen planus (OLP) is a chronic inflammatory disease observed in approximately 0.5–2.2% of the population, and it is recognized as a premalignant lesion that can progress into oral squamous cell carcinoma (OSCC). The rate of malignant transformation is approximately 1.09–2.3%, and the risk factors for malignant transformation are age, female, erosive type, and tongue site location. Malignant transformation of OLP is likely related to the low frequency of apoptotic phenomena. Therefore, apoptosis-related genetic factors, like p53, BCL-2, and BAX are reviewed. Increased p53 expression and altered expression of BCL-2 and BAX were observed in OLP patients, and the malignant transformation rate in these patients was relatively higher. The involvement of microRNA (miRNA) in the malignant transformation of OLP is also reviewed. Because autophagy is involved in cell survival and death through the regulation of various cellular processes, autophagy-related genetic factors may function as factors for malignant transformation. In OLP, decreased levels of ATG9B mRNA and a higher expression of IGF1 were observed, suggesting a reduction in cell death and autophagic response. Activated IGF1-PI3K/AKT/mTor cascade may play an important role in a signaling pathway related to the malignant transformation of OLP to OSCC. Recent research has shown that miRNAs, such as miR-199 and miR-122, activate the cascade, increasing the prosurvival and proproliferative signals.

Malignant transformation of oral lichen planus: where are we now?

Oral lichen planus (OLP) is a very prevalent disease whose main clinical feature is the appearance of white hyperkeratotic reticular lesions, which may or may not be accompanied by erosive and/or atrophic lesions, among others. One of the most relevant aspects of the process is its current consideration as an oral potentially malignant disorder (OPMD), although this is currently the subject of considerable controversy. A review of the literature was carried out in order to critically analyze the controversies surrounding the consideration of OLP as an OPMD, where they originate from and the available evidence that has led to the conclusion that OLP patients are at risk of developing oral cancer. The controversies over the definitive acceptance of OLP as an OPMD were classified as controversies related to the lack of widely accepted diagnostic criteria for OLP; controversies related to histopathological aspects of OLP and the presence of epithelial dysplasia as a diagnostic exclusion criterion; and controversies related to clinical aspects of OLP (which in turn were subclassified into: controversies on how to interpret reticular lesions in OLP, on the nature of the white plaques that appear in OLP; on the changing character of reticular lesions in OLP; and on the criteria for accepting a case as a true malignant OLP). Furthermore, evidence to justify the acceptance of OLP as an OPMD was in depth reviewed, including the molecular evidence, evidence from research studies with the highest evidence design -systematic reviews and meta-analyses-, and evidence from case series reporting strong results. This paper presents the reasons for the controversies as well as the evidence that allows us to accept that OLP behaves as an OPMD.

There is probably a low risk of experiencing a malignant transformation of oral lichen planus

There is probably a low risk of experiencing a malignant transformation of oral lichen planus

Association of MAPK and its regulatory miRNAs (603, 4301, 8485, and 4731) with the malignant transformation of oral lichen planus.

Oral lichen planus (OLP) is a potentially malignant oral lesion that may transform into oral squamous cell carcinoma (OSCC). The purpose of this study was to assess the level of expression of MAPK/ERK1/2 gene, and microRNA (miR)-603, 4301, 8485, and 4731 in the MAPK signaling pathway in OLP and OSCC lesions. This case-control study evaluated 26 OSCC, 20 OLP and 20 healthy control tissue specimens. After RNA extraction, the respective miRNA and MAPK/ERK1/2 mRNA levels were assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR). Significant upregulation of MAPK/ERK1/2 gene was noted in the OLP and OSCC specimens compared with healthy controls (p < 0.001). The expression level of miR-4731 was significantly lower in the OLP and OSCC specimens than in the healthy specimens (p < 0.001). The expression of MiR-603 was the lowest in OLP, followed by OSCC and then the control group (p < 0.001). No significant difference was found in miR-4801 levels between OSCC and OLP specimens compared with healthy controls (p = 0.43 and p = 0.86, respectively). In addition, a non-significant decrease in miR-8485 levels was noted in the OSCC and OLP specimens compared with healthy controls (p = 0.98 and p = 0.61, respectively). A significant decrease in level of miR-603 was noted in OLP compared with OSCC group (p < 0.001). The miR-4801 and miR-8485 expression levels were directly correlated with MAPK/ERK1/2 mRNA expression (p = 0.01). Higher expression level of MAPK/ERK1/2, miR-603, miR-4801, and miR-4731, and lower expression level of miR-8485 were correlated with significantly lower overall survival rate in OSCC patients. The increased expression of MAPK/ERK1/2 and decreased expression of miR-603 and miR-4731 are associated with greater risk of OLP malignant transformation and poor histopathological characteristics of OSCC.

Salivary Antisense Non-Coding RNA In the INK4 Locus &amp; Maternal Expressed Gene 3 as early biomarkers in Detection of Malignant Transformation of Oral Lichen Planus

Oral lichen planus (OLP) is a potentially malignant lesion. It is crucial to properly identify patients at risk of malignant transformation. LncRNA antisense non-coding RNA in the INK4 locus (ANRIL) has been known to advance tumor progression. Another type of lncRNAs is maternal expressed gene (MEG3) which is a tumor suppressor gene that can inhibit the advancement of malignancy. The goal of this study was to outline the relative fold expression of ANRIL and MEG3 in OLP and oral squamous cell carcinoma (OSCC). The study included 20 histopathologically diagnosed OLP patients and 10 patients with OSCC. The relative fold expression of ANRIL and MEG3 in the OLP group was compared to OSCC group using qRT-PCR. The results showed that the relative fold expression of ANRIL was significantly increase in the OSCC compared to OLP group (p<0.01). ROC analysis showed that with cut-off value of 4.1 relative fold expression of ANRIL with sensitivity 0.8, specificity 0.7 and AUC 0.85. The decrease in MEG3 was insignificant. ANRIL relative fold expression could perform an essential part in OSCC progression, and could assist in the future as a potential biomarker for malignant transformation of OLP.

Genotyping of the C>T allele of rs16906252, predictor of O16-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, in erosive atrophic lesions of oral lichen planus.

DNA promoter methylation is usually an early stage in carcinogenesis process, including oral cancer. The purpose of this study was to investigate the association between T allele of specific single nucleotide polymorphism (SNP) C>T rs 16906252 and O16-methylguanine-DNA methyltransferase (MGMT) methylation as prospective biomarkers of malignant transformation in oral lichen planus (OLP), a chronic autoimmune mucocutaneous disease. This research is an observational, analytical case-control study where a total of 85 subjects (43 control individuals and 42 OLP patients) participated. The samples (mouthwashes) from all volunteers were analyzed, and DNA extraction was carried out. The genotyping of the rs 16906252 SNP in the MGMT gene was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses of Student t test and multiple logistic regressions were used. C>T genotype in the control and OLP groups was detected in 2.3% and 19.0%, respectively. The presence of this genotype was associated with methylation of the MGMT gene. In fact, taking into account age and gender, subjects with C>T genotype were 10.5 (95% CI 1.03-106; P=0.047) times more likely to methylate promoter region of the MGMT gene. These findings indicate that C>T allele of rs 16906252, predictor of MGMT promoter methylation status, may be an important feature in the clinical prognosis of premalignant lesions of OLP, although this finding requires further clinical and laboratory investigation.

The Malignant Transformation of Oral Lichen Planus and Oral Lichenoid Lesions, a Case Report and Review of the Literature

The Malignant Transformation of Oral Lichen Planus and Oral Lichenoid Lesions, a Case Report and Review of the Literature

Evaluation of the role of YKL-40 and interleukin-8 (IL-8) as biomarkers for malignant transformation in oral lichen planus

Objective: This investigation was conducted to measure the levels of serum and salivary YKL- 40 and IL-8 in patients suffering from OLP and OSCC to assess their potential role as biomarkers of oral cancer. Methods: Forty five subjects with age ranging from 30 to 70 years were distributed into 3 groups; 15 patients having atrophic and/or erosive OLP, 15 patients suffering from OSCC and 15 systemically healthy control individuals.YKL-40 and IL-8 were identified in serum and saliva samples utilizing enzyme-linked immunosorbent assays. Results: Serum YKL-40 and salivary levels of YKL-40 and IL-8 in patients with OSCC and OLP were significantly higher than the healthy control group. In order to differentiate patients having OLP from those suffering from OSCC, our study utilized the analysis of the receiver operating curve (ROC) which showed an AUC of 0.878, 0.789, 0.789 and 0.7 for serum YKL-40, salivary YKL-40, serum IL-8, and salivary IL-8, respectively. Serum YKL-40 had the highest diagnostic accuracy revealing 93 % sensitivity and 73 % specificity. That has been followed by salivary YKL-40 and serum IL-8, both revealing a good diagnostic accuracy with 93%, 80 % sensitivity, and 60%, 73.3 % specificity respectively. Salivary IL- 8 as well yielded a good diagnostic accuracy and revealed degrees of sensitivity (80%) and specificity (63%). Cut off values of the biomarkers under investigation has been selected according to the distribution of sensitivities and specificities Conclusion: YKL-40 and IL-8 might be counted as biomarkers for identifying cancerous changes of OLP and the initial stage of OSCC.

Increased salivary aldehyde dehydrogenase 1 in non-reticular oral lichen planus.

BackgroundOral lichen planus is a potentially malignant disorder. One of the malignant transformation markers is cancer stem cells. One of the proposed marker for the detection of cancer stem cells's in head and neck cancer is aldehyde dehydrogenase. Recently it is shown that aldehyde dehydrogenase 1 expression in tissue samples is associated with oral lichen planus malignant transformation.ObjectiveThis study evaluates salivary aldehyde dehydrogenase 1 in oral lichen planus.MethodThirty patients and 30 age and sex-matched healthy volunteers were recruited. Oral lichen planus was diagnosed based on the modified World Health Organization criteria. Subjects in the case group were divided into reticular and non-reticular forms. Unstimulated salivary samples were collected at 10-12 AM. Saliva concentrations of aldehyde dehydrogenase 1 were measured by ELISA.ResultsThe differences between aldehyde dehydrogenase levels in the oral lichen planus group compared with the control group were not significant but aldehyde dehydrogenase in non-reticular oral lichen planus was significantly higher than that of the reticular form.Limitations of the studyThis is a cross-sectional study, thus longitudinal studies in oral lichen planus may present similar or different results.ConclusionsThe mechanism of malignant transformation in oral lichen planus is not defined. Previous analyses revealed that the aldehyde dehydrogenase 1 expression is significantly correlated with increased risk of transformation. This finding is consistent with our results because in the erosive and ulcerative forms of oral lichen planus, which have an increased risk of transformation, salivary aldehyde dehydrogenase 1 was overexpressed. A higher salivary aldehyde dehydrogenase level in non-reticular oral lichen planus can be a defensive mechanism against higher oxidative stress in these groups. Aldehyde dehydrogenase may be one of the malignant transformation markers in oral lichen planus. Further studies are needed for introducing aldehyde dehydrogenase as a prognostic indicator in certain lesions.

Role of Cathepsin B as a Marker of Malignant Transformation in Oral Lichen Planus: An Immunohistochemical Study.

Malignant transformation of Oral Lichen Planus (OLP) remains a much discussed but very less understood realm. Various hypotheses and theories have been put forward to explain the same. Malignant transformation is a complex interplay of epithelial mesenchymal factors acting in tandem. This study tries to identify and asses the stromal changes that pave the way for epithelial migration using Cathepsin B (CB) a cysteine protease belonging to the Cathepsin family. Various studies have been done to study its role in human cancers which have proven that CB helps mark and identify tissue digestion. The purpose of this study was to evaluate the expression of CB, in OLP and examine its possible role in malignant transformation. Immunohistochemical analysis of CB expression was done in 50 OLP tissues along with 10 normal mucosa tissue and 10 Oral Squamous Cell Carcinoma (OSCC) cases (control groups). Evaluation was done on the basis of intensity of staining. The intensity was graded in all the cases by assigning values of 0 to 4 in ascending order. Two other observers evaluated the staining and intensity independently and the average of the observations was taken. A variable staining pattern in both the stroma and the cytoplasm of the epithelial cells was noticed. The staining intensity was clearly increased in OLP tissues when compared to normal control tissue and OSCC which served as our positive control. The staining patterns in tissues of OLP and OSCC to Cathepsin B were similar. The staining intensity of Cathepsin B was observed to be increased in both these groups of tissues. This study demonstrated a significantly increased expression of CB in OLP. This may be correlated to a possible indicator for its eventual malignant transformation. This overexpression of CB amounts to an array of stromal changes that take place and different mechanisms that get activated underneath the epithelium leading to the formation of what is known as a tumour microenvironment, a well proven entity. We hypothesize that it is this which felicitates the invasion of the overlying epithelial cells.

Clinicopathological Profile and Malignant Transformation in Oral Lichen Planus: A Retrospective Study.

Objectives:The aim of this study was to analyze the histopathologically diagnosed cases of oral lichen planus (OLP) in terms of age, gender, clinical variant, site, hyperpigmentation, systemic illness, grade of dysplasia, and associated malignant transformation. This study also intended to do a review of reported cases of OLP with malignant transformation.Materials and Methods:One hundred and forty-three cases of histopathologically diagnosed OLP between 2010 and 2016 were retrospectively reviewed. Demographic and clinicopathological data including malignant transformation were obtained. The data obtained were analyzed using the Statistical Package for the Social Sciences (SPSS) software for Windows version 20.0 (IBM SPSS, SPSS Inc., Chicago, IL, USA). A review of published literature on OLP with malignant transformation was also done from 1988 to 2017 and tabulated.Results:OLP in this study showed a male predilection with most of the patients in the third decade. The buccal mucosa (bilateral presentation) was the most common site (79.72%), and reticular type was the most common clinical type (79.02%) followed by erosive type (20.98%). The majority (92.31%) of cases were diagnosed with OLP without dysplasia. The rest (7.69%) of dysplastic cases were predominantly seen in the buccal mucosa of 58 years and above, female patients manifesting mainly as erosive type. Two patients (1.4%) previously diagnosed clinically and histopathologically as OLP developed oral squamous cell carcinoma.Conclusion:The present investigation revealed the predominance of OLP among middle-aged male population and the prevalence of bilateral involvement of buccal mucosa. Two of our cases showed malignant transformation over an average period of 3.5 years. The outcome of this study emphasizes the role of clinical follow-up of patients with OLP.

Image-based DNA ploidy analysis aids prediction of malignant transformation in oral lichen planus

To investigate the potential of image-based DNA ploidy analysis to predict malignant transformation in patients with oral lichen planus (OLP). DNA ploidy analysis was performed on biopsy samples from 14 patients with OLP who underwent malignant transformation. As controls, 42 OLP lesions showing unusual clinical features suggesting a transformation risk and 68 samples of clinically and histologically typical OLP were included. Cases with dysplasia on initial biopsy were excluded. Eighty fibroepithelial polyps acted as methodologic controls. Epithelial nuclei were isolated from formalin-fixed paraffin embedded biopsy samples and monolayers stained with Feulgen for automated image cytometry to establish DNA content. Ploidy status was correlated to outcome using Kaplan-Meier analysis and log-rank Mantel-Cox tests. All controls and typical OLP were diploid and none underwent malignant transformation in mean follow-up of 14years (10-18years). One unusual OLP developed carcinoma and all were diploid. The 14 patients with transformation developed 21 carcinomas. In the 11 patients who had a prior biopsy, 4 were aneuploid. DNA ploidy analysis predicted malignant transformation in more than one third (36.4%) of patients with OLP with a preceding biopsy (n=11). This premalignant nature could not have been diagnosed clinically or by histologic dysplasia assessment.

Myeloid cell leukemia-1 is a molecular indicator for malignant transformation of oral lichen planus

Oral lichen planus (OLP), characterized by a chronic mucocutaneous inflammatory condition, is a common disease of the oral cavity. Retrospective and prospective epidemiological data suggest that OLP is considered to have malignant potential. However, it is unclear as to which types of molecules may cause malignant transformation of OLP. In the present study, the presence of myeloid cell leukemia-1 (Mcl-1) and B-cell lymphoma-2 (Bcl-2) was studied by western blot analysis in 11 OLP and three normal oral mucosa (NOM) samples and in two human oral cancer cell lines. The functional role of Mcl-1 in oral cancer cells was analyzed using a trypan blue exclusion assay and soft agar assay. Mcl-1 was strongly expressed in the OLP and the two oral cancer cell lines compared with NOM, whereas Bcl-2 was not. Sorafenib and mithramycin A decreased cell viability in MC-3 and HSC-3 oral cancer cells and at same concentration they reduced the expression level of Mcl-1 in the two cell lines. The two chemicals affected Mcl-1 protein and significantly inhibited neoplastic cell transformation in the two cell lines. We suggest that the malignant potential of OLP may be associated with the expression of Mcl-1, and that downregulation of Mcl-1 may prevent malignant transformation of OLP to oral cancer.

Evaluation of Potential Risk Factors that contribute to Malignant Transformation of Oral Lichen Planus: A Literature Review.

Many studies have suggested that a lesion originally diagnosed as oral lichen planus (OLP) has different possibilities of undergoing malignant transformation in time, although these findings remain a controversial issue; for example, some studies reported different values of potential malignancy of OLP. World Health Organization (WHO) classifies OLP as a "potentially malignant disorder" with unspecified malignant transformation risk, and suggests that OLP patients should be closely monitored. Numerous studies have attempted to confirm the malignant transformation potential of OLP. The Cochrane Controlled Trials Register, Medline and EMBASE databases, PubMed, Google Scholar, Ovid, Up To Date, BMJ Clinical Evidence, MD Consult, and Science Direct were searched for papers published between 1997 and 2015. The medical subject heading search terms were "lichen planus," "oral lichen planus," "erosive oral lichen planus," "dysplasia," "oral precancerous condition," "oral premalignant condition," oral cancer, oral squamous cell carcinoma (OSCC), and atrophic lichen planus. A total of 120 English language abstracts were reviewed, and 50 relevant articles identified. Because of the extensive literature on the association between OLP and SCC, we have divided the data into genetic and non-genetic factors for more accurate assessment. In this evidence base, malignant transformation ranges from 0 to 37% with a mean of 4.59%. The highest rate of malignancy was noted in erythematosus and erosive lesions. In this way, follow-up of OLP patients could be carried out more efficiently and appropriately. Oral lichen planus is a premalignant lesion. All types of OLP in any site of oral mucosa must be monitored regularly.

Role of miRNA in the malignant transformation of oral lichen planus

Role of miRNA in the malignant transformation of oral lichen planus

Oral lichen planus (OLP), oral lichenoid lesions (OLL), oral dysplasia, and oral cancer: retrospective analysis of clinicopathological data from 2002-2011.

This 10-year retrospective study analyzed the incidence of malignant transformation of oral lichen planus (OLP). The study also included dysplasia and oral lichenoid lesion (OLL) in the initial biopsy as a potential differential diagnosis. A total of 692 scalpel biopsies were taken from 542 patients (207 [38.2%] men and 335 [61.8%] women). Clinical and histopathological parameters were analyzed. The parameters gender (p = 0.022) and smoking behavior (p < 0.001) were significantly associated with the severity of diagnosis. Mucosal lesions with an ulcerative appearance (p = 0.006) and those located on the floor of the mouth (p < 0.001) showed significantly higher degrees of dysplasia or were diagnosed as oral squamous cell carcinoma (OSCC). Smoking and joint disease appeared to be significant risk factors. Treatment with tretinoin in different concentrations (0.005-0.02%) significantly improved diagnosis. Twelve patients (8 female, 4 male) showed malignant transformation to OSCC within an average period of 1.58 years. The malignant transformation rate (MTR) was higher for OLL (4.4%) than OLP (1.2%). If the first biopsy showed intraepithelial neoplasia, the risk of developing OSCC increased (by 3.5% for squamous intraepithelial neoplasia (SIN) II and by 6.7% for SIN III). Although we cannot rule out that OLP is a premalignant oral condition, we can confirm that OLP had the lowest MTR of all diagnoses.

The malignant transformation of oral lichen planus and oral lichenoid lesions: A systematic review

Determining the potential for malignant transformation of oral lichen planus (OLP) is complicated by difficulties in diagnosis, differentiation from oral lichenoid lesions (OLLs) and the phenomenon of premalignant lesions' exhibiting lichenoid characteristics. The authors of this systematic review evaluated evidence regarding malignant transformation of OLP and characterized transformation prevalence, clinical characteristics of OLP lesions developing into squamous cell carcinoma (SCC) and time to transformation. The authors searched PubMed, Embase and Thomson Reuters Web of Science in a systematic approach. They evaluated observational English-language studies involving human participants published in peer-reviewed journals. Inclusion required patients to have the diagnosis of OLP or OLL as confirmed with biopsy results on initial enrollment. They excluded all patients who had dysplasia on initial biopsy of OLP or OLL lesions. Sixteen studies were eligible. Among 7,806 patients with OLP, 85 developed SCC. Among 125 patients with OLL, four developed SCC. The rate of transformation in individual studies ranged from 0 to 3.5 percent. The overall rate of transformation was 1.09 percent for OLP; in the solitary study in which investigators evaluated OLL, the rate of transformation was 3.2 percent. Patients' average age at onset of SCC was 60.8 years. The authors noted a slight predominance of female patients among those who experienced malignant transformation. The most common subsite of malignant transformation was the tongue. The average time from diagnosis of OLP or OLL to transformation was 51.4 months. A small subset of patients with a diagnosis of OLP eventually developed SCC. The most common demographic characteristics of patients in this subset were similar to the most common demographic characteristics associated with OLP in general (that is, being female, being older and being affected in areas common to this condition). It is prudent for clinicians to pursue continued regular observation and follow-up in patients with these conditions, even in patients who do not fit a traditional high-risk category for oral SCC.