Clinicopathological features and malignant transformation of oral lichen planus: A 12-years retrospective study

Abstract

Objective. Oral lichen planus (OLP) is known to be associated with the risk of developing oral squamous cell carcinoma (OSCC). The objective of this study was to investigate the clinicopathological features of OLP and the prevalence of malignant transformation in this setting. Materials and methods. This retrospective study was carried out on 204 medical records of patients with histologically proven OLP who received long-term follow-up (range 6 months–12 years). Data were entered in an informatic database. The statistical analysis, when needed, was performed with the chi-squared test for significance (p < 0.05). Results. At the moment of the diagnosis, out of 204 patients (163 female and 41 male; mean age 54.5 years), 107 patients (52.45%) suffered from systemic chronic diseases, in particular 46 (22.5%) from hepatitis C. Clinically, the reticular form of OLP was the predominant one and most patients had multiple oral sites of involvement. Fourteen patients showed extra-oral lesions. A percentage of malignant transformation less than 1% was found. In fact, two patients (0.98%) underwent a malignant transformation at a site previously diagnosed as OLP. Conclusions. At present, OLP is accepted as being a potential malignant disorder, therefore lifelong follow-up is recommended.     

Oral lichen planus and malignant transformation: a retrospective follow-up study of clinical and histopathologic data.

OBJECTIVE: Patients in the stomatology service of the Department of Oral Surgery and Stomatology who were clinically and histopathologically diagnosed with oral lichen planus (OLP) in the years 1995 to 2001 were examined for a possible malignant transformation of a previously biopsied OLP site. METHOD AND MATERIALS: For the 145 patients included, the recordings were searched for initial localization and type of OLP lesion, potential noxious agents, distribution between symptomatic and asymptomatic OLP types, and for a malignant transformation of a known OLP site during the follow-up period up to December 2003. RESULTS: The group comprised 47 men and 98 women with a mean age of 56.3 years. Of the 497 lesions, almost half were classified as reticular or papular, predominantly located on the buccal mucosa, gingiva, and borders of the tongue. Four patients did not adhere to their scheduled control visits and were dropped from the study. During the follow-up period 4 patients developed malignant transformation of OLP. In 3 of these cases, dysplasia was present at the initial diagnosis of OLP. This results in a malignant transformation rate of 2.84% among the remaining 141 patients; if the 3 patients with initial dysplasia are excluded, the rate drops to 0.71%. CONCLUSIONS: Until further knowledge is derived from large prospective studies, the data supporting or negating a potential malignant character of OLP lesions remains inconclusive. Special emphasis has to be directed toward unified inclusion and exclusion criteria regarding clinical and histologic findings and identifiable risk factors to allow the comparison of different studies.     

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

BackgroundDetermining 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&apos; 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.Types of Studies ReviewedThe 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.ResultsSixteen 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&apos; 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.Practical ImplicationsA 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.     

Oral lichen planus: a retrospective study of 690 British patients

OBJECTIVE: This is the largest UK patient group with oral lichen planus (OLP) to be studied in terms of the demographic and clinical characteristics. MATERIALS AND METHODS: Data were taken from the medical records of 690 consecutive patients referred to Oral Medicine subsequently found to have clinical, and usually histopathological confirmatory features of OLP. Over two-thirds (68.7%) of the patients were Caucasians. RESULTS: Eighty-two per cent of the patients had been referred to a specialist Oral Medicine service by general dental practitioners, 62% of the patients being referred as a consequence of oral mucosal and/or gingival pain. Reticular OLP was the most common intra-oral presentation, but 60% of such lesions were accompanied by other clinical types of OLP. 95% of lesions were bilateral. About 13% of patients reported symptoms or signs, or had a known history of lichen planus or possible lichen planus affecting non-oral epithelia. In only 13% of patients did all signs and symptoms of OLP resolve within 12-246 months (median 35 months). A malignant transformation rate of 1.9% was observed in the present group. CONCLUSIONS: Oral lichen planus in UK persons almost always gives rise to bilateral reticular OLP, rarely resolves spontaneously, and has a low rate of malignant transformation.     

Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus

ObjectiveOral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases.MethodsMetabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease.ResultsIn total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP.ConclusionThe dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease.     

口腔扁平苔藓724例的回顾性分析

目的对口腔扁平苔藓（oral lichen planus，OLP）的临床及病理学特点进行大样本量的研究。方法对上海交通大学医学院附属第九人民医院·口腔医学院口腔黏膜科1978年1月至2006年10月的存档病例进行筛选，选出临床及病理诊断为OLP且半年内至少复诊1次的病例共724例，记录病例的性别、年龄、部位、类型、家族史、病理活检、随访时间、是否癌变及系统性疾病史，并对病例资料进行统计学分析。结果本组OLP病例的随访时间从1个月到259个月（平均随访时间为21个月）。在724例患者中，68．23％是女性，31．77％是男性。OLP的累及部位依次为颊部、舌背、舌腹、唇部、牙龈、腭部、口底。在原发的病损类型中，大部分为斑纹型，占总数的53．82％。病损发生在两个部位以上的OLP患者占总数的48．76％。15例发生了癌变，癌变率为2．07％。结论OLP具有癌变潜能，长时间及规律的随访对于监控OLP的恶性转变过程至关重要。     

Evaluation on Malignant Transformation of Oral Lichen Planus

目的：口腔扁平苔藓（oral lichen planus,OLP)是否属于癌前病变，至今仍存在较大的争论。本文的目的在于评估OLP的癌变性质。方法：报告1995－2002年之间9例OLP的癌变病例。结果：5例OLP患者同时或继发为口腔鳞状细胞癌，1例为疣状癌，3例为上皮异常增生。其中7例发生在原OLP存在的部位，1例发生在其它部位，1例在同一部位同时存在OLP和鳞状细胞癌。OLP的癌变常发生在糜烂型和萎缩型，发生于颊粘膜，舌或牙龈。根据所制定的OLP的诊断及癌变标准，4例OLP患者发生了癌变。结论：OLP具有一定的癌变潜力，对OLP患者应每年随访2－4次，尤其是对发生在颊粘膜，舌或牙龈的糜烂型和萎缩型的患者。     

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口腔扁平苔藓(oral lichen planus,OLP)是一种常见的口腔黏膜慢性炎性疾病,WHO将其列入潜在恶性病变(potentially malignant disorders)的范畴。有关OLP癌变的研究目前主要集中在流行病学调查、癌变危险性预测、癌变机制、化学预防等方面,而对其是否癌变近年产生疑问和争议。本文就OLP癌变的相关研究进展进行综述。     

Impact of oral potentially malignant disorders on quality of life

Background

Oral potentially malignant disorders (OPMDs) could have a significant psychological impact on patients, principally because of the unknown risk of malignant transformation, while the physical and functional impairments could differ. This study aimed to assess the impact of three different OPMDs and their disease stages on the quality of life (QoL) of affected patients.

Methods

Oral leukoplakia (OL), oral lichen planus (OLP) and oral submucous fibrosis (OSF) patients who were undergoing treatment at an oral medicine clinic of a dental teaching hospital in India were the study population. All subjects completed the recently developed OPMDQoL questionnaire and a short form 12 item (version 2) health survey questionnaire (SF‐12v2). OPMDQoL questionnaire consists of 20 items over four dimensions. A higher score denotes poor OHRQoL. SF‐12v2 has two components, a Physical Component Summary (PCS) and Mental Component Summary (MCS).

Results

A total of 150 subjects (50 each of OL, OLP and OSF) participated. OL patients (37.7 ± 7.9) reported significantly better OPMDQoL scores than OLP (47.3 ± 5.8) and OSF (45.4 ± 9.2) patients. OLP patients reported significant problems in obtaining a clear diagnosis for their condition, more so than the other OPMDs. OL patients reported fewer problems for the dimension, “physical impairment and functional limitations” than the OLP and OSF patients. A significant trend was observed with the overall OPMDQoL and MCS, deteriorating as the disease stage increased.

Conclusions

OLP and OSF have a significant impact on the QoL of affected individuals: OL less so. Increasing stage of the disease is associated with worsening QoL.     

Oral lichen planus in Arab countries : a review

Oral lichen planus (OLP) is a chronic mucocutaneous inflammatory disease of unknown etiology with a potential for malignant transformation. Little is known about the epidemiology of this condition in the Arab world. A computer‐based literature search was conducted using relevant keywords to retrieve studies conducted in Arab world pertaining to OLP, 28 articles were identified initially. After screening for exclusion criteria/retrieving full texts, a total of 15 articles were used for this review. Three studies were cross‐sectional and found a prevalence ranging from 0.35% to 1.7%. Studies about risk factors and prognostic markers were conducted in clinical settings, using a case–control design mostly (n = 9), cohort (n = 2), and clinical trial (n = 1). Genetic expressions of various proteins (e.g., BCL family), cultural determinants (Deram chewing), bacterial and viral infections [Helicobacter pylori and Hepatitis C virus (HCV)] were among factors investigated. Evidence extracted from these studies shows a possible link between OLP and Deram use, H. pylori and HCV Infections with a prevalence of the latter infection ranging from 14.7% to 26.3% in patients with OLP. However, paucity of population‐based studies limits generalizability of such evidence. Future studies in the Arab world should focus upon surveying the extent of OLP, identifying cultural risk factors, utilization of OLP genetic markers in diagnostic, and prognostic applications.     

人β防御素2与口腔扁平苔藓相关性的研究进展

口腔扁平苔藓(oral lichen planus,OLP)是一种常见的口腔黏膜慢性免疫性炎症疾病,OLP的病因和发病机理目前尚未阐明,在临床诊疗过程中存在着诸多问题且OLP存在癌变风险,故OLP的发生发展及临床诊疗方面的研究历来受到重视.近年来的一些研究表明,OLP的发生与人β防御素2(humanβdefensin-...     

High percentage of oral lichen planus and lichenoid lesion in oral squamous cell carcinomas

Objective: Oral lichen planus (OLP) and lichenoid lesions (OLL) are regarded as precursor lesions of oral squamous cell carcinoma (OSCC) with potential for malignant transformation. This potential is not clear due to difficulties in diagnosis of OLP and OLL. Our aim was therefore to evaluate previously identified OLP and OLL as precursor lesions in OSCC and to identify cancer related etiological factors such as smoking and alcohol consumption.

Material and methods: We retrospectively reviewed all cases (total 323, comprising 164 females and 159 males) with OSCC treated at the Department of Oral and Maxillofacial Diseases and Surgery, Helsinki University Hospital during 2015. Confirmed by histopathological biopsy, 58 (17.9%) had OLP and 13 had OLL (4.0%) as precursor lesion.

Results: Patients with OLP were slightly older than those without it. OLP was more common in females than in males (p?p?=?.006) and cancer relapses less common (p?=?.005). Smoking was less frequent in patients with OLP and OLL (p?p?Conclusion: Our findings confirm the importance of active follow-up of all patients with OLP and OLL even in patients who do not fit a traditional high-risk category for OSCC.     

细胞自噬在口腔扁平苔藓恶变中作用的研究进展

口腔扁平苔藓(OLP)是一种常见的口腔黏膜炎症性疾病,易复发并存在恶变的可能,具体的病因和发病机制尚不清楚。细胞自噬是真核细胞生物中高度保守的生命现象,作为程序性细胞死亡的方式之一,在维持细胞内环境的稳态方面起到重要作用。目前关于细胞自噬与OLP发病及恶变的关系的相关报道较少,本文就细胞自噬与口腔扁平苔藓的联系作一探讨。     

The possible premalignant character of oral lichen planus and oral lichenoid lesions: a prospective study

OBJECTIVES: The possible malignant transformation of oral lichen planus (OLP) is the subject of an ongoing and controversial discussion in the literature. The main criticism of studies on this subject relates to the lack of sufficient data to support the initial diagnosis of OLP in cases that finally developed into squamous cell carcinoma. We describe the possible premalignant character of OLP and oral lichenoid lesions (OLL) of a prospectively followed cohort of patients with detailed documentary data. STUDY DESIGN: A study group of 173 patients, 62 patients diagnosed with OLP and 111 patients with OLL, according to revised, modified World Health Organization diagnostic criteria, was followed up from 6.6 to 72.0 months (mean, 31.9 months). The expected number of patients with oral cancer in the group of patients with OLP and in the group of patients with OLL was estimated by comparing the number of patients, their ages, sex, and the length of follow-up to annual incidence rates of oral cancer for the general Dutch population, to explore the possibility of coincidental carcinomas. The binomial test was used to determine whether the observed number of cases of cancer in the OLP group and the OLL group exceeded the expected numbers. RESULTS: Three of 173 patients (1.7%), 2 men and 1 woman, developed squamous cell carcinomas of the oral mucosa during follow-up. All malignant transformations occurred in the OLL group. The annual malignant transformation rate, based on a mean follow-up of 31.9 months, was calculated as 0.65% per year. A comparison of the expected against actual figures for the development of carcinomas revealed no increase in patients with OLP and a 219-fold increase in patients with OLL, with the latter not statistically significant, but with a P value of .083, suggesting at least a trend. CONCLUSION: Our results give support to the hypothesis that patients with OLL have an increased risk of oral cancer, but this increased risk was not detected in our sample of patients with OLP. Before a final statement with regard to the premalignant character of OLP and OLL can be formulated, the present follow-up study should be prolonged and expanded with a larger number of patients. Until then, we advise that patients with OLP and OLL should undergo biannual follow-up examinations. Follow-up will be particularly important in patients with OLL who have atrophic/erosive/ulcerative lesions.     

A clinical study of 674 patients with oral lichen planus in China

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disease with different clinical presentations that can be classified as reticular, atrophic or erosive. Although OLP is a relatively common disorder, the reports comprising large numbers of OLP patients with specific character are lacking in the literature. The purpose of this paper was to describe the clinical characteristics of OLP in 674 Chinese patients. METHODS: A total of 674 charts of patients with histologically confirmed OLP were collected from Stomatological Hospital of Wuhan University between 1963 and 2003. RESULTS: Of the 674 patients, 65.9% were women and 34.1% were men. The most common clinical presentation was the reticular type (51.3%), and symptomatic OLP was noted in 67.5% of the patients, mainly in those with the erosive form. The erosive presentations showed significantly longer duration, more sites affected and a much greater old patients predominance than reticular or atrophic ones. About 90.9% of the patients had multiple oral sites of involvement and isolated lower lip lichen planus were observed in 60 cases (8.9%) and isolated gingiva lichen in only one case (0.2%). Skin involvement of lichen planus was found in 11.4% of patients. No statistically significant differences could be identified between OLP and diabetes, cardiovascular disease, smoking or alcohol use. Precipitating factors that resulted in an exacerbation of the disease were frequently noted and included foods, stress, dental cusp and poor oral hygiene. The transformation of OLP into malignancy was observed in four patients at sites previously diagnosed by clinical examination as erosive or atrophic lichen planus. CONCLUSIONS: Patients with OLP in China usually present with distinctive clinical morphology and characteristic distribution and few may display lesions with a confusing array of forms mimicking other diseases. A long time follow up is of utmost importance to detect its malignant transformation.     

In situ carcinoma developed over oral lichen planus: a case report with analysis of BUB3, p16, p53, Ki67 and SOX4 expression

Oral lichen planus (OLP) represents a common mucocutaneous disease. Various authors have suggested that OLP has malignant potential; however, the mechanisms involved in malignant transformation have not yet been elucidated. A 79-year-old man presented a white lesion for five months in the buccal mucosa diagnosed as OLP. After two months using 0.05% clobetasol ointment for treatment, the lesion became ulcerated. A new biopsy of the same lesion was performed, and histological analysis showed an in situ oral carcinoma (ISOC). An immunohistochemistry panel was performed, and p16 expression was negative in OLP, however, it showed weak cytoplasmic staining in ISOC. There was strong nuclear BUB3 staining in both OLP and ISOC areas. p53 showed less intense nuclear staining in both regions. Ki67 was negative in OLP area, but showed nuclear staining in the ISOC. SOX4 was negative in both studied areas. BUB3 expression, first reported in this case, and the p16 expression may suggest some influence of these genes on pathogenesis or malignant potential of OLP.     

Oral lichen planus: Malignant potential and diagnosis

Oral lichen planus (OLP) is one of the most common diseases of the oral mucosa. Clinically, it has specific and clearly identifiable features; bilateral symmetric presentation showing a lace-like network of fine white lines (known as Wickham's striae) is an essential element of OLP even if the lesion exhibits a mainly atrophic and erosive pattern. There are various lesions that resemble OLP clinically and histologically. These lesions are widely referred to as lichenoid reactions or lichenoid lesions (OLLs). OLLs include contact hypersensitivity to dental materials, drug-induced lichenoid lesions, lichenoid reactions in chronic graft-versus-host disease, and other lesions that resemble OLP. The risk of malignant transformation of OLP is the subject of ongoing debate in the literature. Some authors have suggested that only OLLs, but not OLP, are of a premalignant nature and thus, should be categorized as “other dysplastic conditions.” Contrary to this suggestion, many cases of oral squamous cell carcinoma (OSCC) developing in patients with OLP presenting with no epithelial dysplasia have been reported. In addition, it has been reported that multiple events including multifocal dysplasia and/or OSCC subsequently occurred in some patients with OLP, suggesting possible field cancerization in OLP. In this paper, differential diagnosis between OLP and OLLs and their malignant potential are reviewed.     

Progressive increase of human papillomavirus carriage rates in potentially malignant and malignant oral disorders with increasing malignant potential

Introduction:  We investigated the potential role of human papillomaviruses (HPVs) in potentially malignant oral disorders, oral leukoplakia (OL) and oral lichen planus (OLP), and in oral squamous cell cancer (OSCC) in an Eastern Hungarian population with a high incidence of OSCC.
Methods:  Excised tumor samples (65 OSCC patients) and exfoliated cells from potentially malignant lesions (from 44 and 119 patients with OL and OLP, respectively) as well as from healthy controls (72 individuals) were analysed. OLPs were classified based on clinical appearance, 61 patients had erosive–atrophic lesions (associated with higher malignancy risk, EA-OLP) and 58 had non-erosive non-atrophic lesions (with lower risk of becoming malignant, non-EA-OLP), respectively. Exfoliated cells collected from apparently healthy mucosa accompanied each lesion sample. HPV was detected by MY/GP polymerase chain reaction (PCR) and genotyped by restriction analysis of amplimers. Copy numbers in lesions were determined using real-time PCR. Prevalence rates, copy number distributions, and association with risk factors and diseases were analysed using chi-square test, t -test, and logistic regression, respectively.
Results:  We detected HPVs significantly more frequently in lesions than in controls ( P  ≤ 0.001 in all comparisons). HPV prevalence increased gradually with increasing severity of lesions (32.8, 40.9, and 47.7% in OLP, OL, and OSCC, respectively). Copy number distribution patterns roughly corresponded to prevalence rates, but OLP and OL were comparable. HPV prevalence differed significantly between EA-OLP and non-EA-OLP groups (42.6 vs. 22.4%); EA-OLP group showed a prevalence similar to that found in OL.
Conclusion:  HPVs may be involved in the development or progression of not only OSCC but also of potentially malignant oral lesions.     

Cost-effectiveness of screening for the possible development of cancer in patients with oral lichen planus

INTRODUCTION: Several authors have expressed the view that patients with oral lichen planus (OLP) are at increased risk of developing oral cancer. Since OLP cannot be effectively treated, regular screening for the possible development of oral cancer might be considered. OBJECTIVES: (i) To calculate costs and effectiveness of screening for oral cancer in OLP patients with a decision model; (ii) to compare the cost-effectiveness of different screening scenarios; and (iii) to perform a sensitivity analysis of several variables used in this model. METHODS: Costs and effectiveness of a population of 100,000 OLP patients, being either screened or not screened for oral cancer, were calculated for the period of 1 year. Health gain was expressed as quality adjusted live years (QALY's) and equivalent lives saved (ELS). Cost-effectiveness was expressed as extra costs (costs of screening minus costs of no screening) per ELS. Then, the outcome was compared with the cost-effectiveness of a different screening scenario. Finally, the effect of varying the variables: (i) costs of cancer treatment; (ii) annual malignant transformation rate (MTR); (iii) sensitivity and specificity of an oral examination; and (iv) proportion of cancers found in stage I on extra costs per ELS were assessed in a sensitivity analysis. RESULTS: The health gain from screening was 592 QALY's or the equivalent of 23.68 lives saved, costing 1,265,229 dollars, meaning that one ELS costed 53,430 dollars. Increase of cancer-treatment costs will significantly decrease the costs per ELS. When the MTR is lower than 0.4% per year, extra costs per ELS will increase exponentially. The effect of sensitivity and specificity of an oral examination in detecting oral cancer on cost-effectiveness seems to be substantial. When the proportion of cancers found in stage I can be increased from 40% (without screening) up to at least 60% after screening, extra costs per ELS will decrease exponentially. CONCLUSIONS: Screening for oral cancer in OLP patients, based on the presently used model, seems attractive. However, varying the several variables in the decision model has a significant impact on the final costs and effectiveness. Only, when additional information about these variables will become available, a more precise and realistic calculation can be performed.     

Oral lichen planus: malignant transformation and human papilloma virus: a review of potential clinical implications

Oral lichen planus (OLP) occurs in from 2% to 3% of the population and may have a risk of malignant transformation into squamous cell carcinoma (SCC). This risk is not necessarily associated with exposure to tobacco and alcohol. An increased awareness of a possible role of human papilloma virus (HPV) and SCC led us to review a possible association between this virus infection and malignant transformation of OLP. The possible linkage between HPV and the risk of transformation of OLP to malignancy is discussed. Furthermore, management of OLP using immunosuppressive drugs may be associated with enhanced viral replication and could theoretically affect the risk of malignant transformation. Implications for clinical care are discussed.