Elsevier

Oral Oncology

Volume 96, September 2019, Pages 121-130
Oral Oncology

Review
Malignant transformation risk of oral lichen planus: A systematic review and comprehensive meta-analysis

https://doi.org/10.1016/j.oraloncology.2019.07.012Get rights and content

Highlights

  • There is a probably underestimation of the malignant transformation potential of OLP.

  • Epithelial dysplasia should not be considered as an exclusion criterion for the diagnostic of OLP.

  • The most concerns aspects related with the risk of OSCC development in OLP patients are atrophic-erosive lesions in tongue.

  • Patients affected for OLP should be following for long periods, probably full life.

  • Tobacco, alcohol and HCV infection increase the risk of malignant transformation in OLP patients.

Abstract

Objectives

To evaluate current evidence on the malignant transformation of oral lichen planus (OLP), oral lichenoid lesions (OLLs), and oral lichenoid reactions (LRs) and to determine the variables with greatest influence on cancer development.

Material and methods

We searched PubMed, Embase, Web of Science, and Scopus for studies published before November 2018. We evaluated the quality of studies (QUIPS tool). We carried out meta-analyses to fulfill our objectives. We examined the between-study heterogeneity and small-study effects, and conducted sensitivity studies and subgroup analyses.

Results

Inclusion criteria were met by 82 studies (26,742 patients. The combined malignant transformation rate was 1.14% for OLP (95% CI = 0.84–1.49), 1.88% for OLLs (95% CI = 0.15–4.95) and 1.71% for LRs (95% CI = 0.00–5.46). Subgroup analysis revealed a higher malignant transformation rate in studies when the presence of epithelial dysplasia was not an exclusion criterion (p = 0.001), when both clinical and histopathological criteria were used for diagnosis (p < 0.001), when the follow-up was at least 12 months (p = 0.048), and when there was lower risk of potential bias (p = 0.002). Malignant transformation risk factors were: tongue localization (RR = 1.82, 95% CI = 1.21–2.74, p = 0.004), presence of atrophic-erosive lesions (RR = 4.09, 95% CI = 2.40–6.98, p < 0.001), tobacco use (RR = 1.98, 95% CI = 1.28–3.05, p = 0.002), alcohol consumption (RR = 2.28, 95% CI = 1.14–4.56, p = 0.02), and hepatitis C virus infection (RR = 4.46, 95% CI = 0.98–20.22, p = 0.053).

Conclusions

The malignant transformation rates of OLP, OLLs and LRs are underestimated due essentially to restrictive diagnostic criteria, inadequate follow-up periods, and/or low quality of studies.

Introduction

Oral lichen planus (OLP) is an autoimmune chronic inflammatory disease of unknown etiology, characterized by the presence of white reticular lesions sometimes accompanied by erosive and/or atrophic lesions [1]. Most authors consider it a highly prevalent disorder that may develop in up to 2% of the general population [2]. OLP is currently considered an oral potentially malignant disorder (OPMD), although its malignant transformation rate is controversial, largely attributable to the restrictive criteria for its diagnosis [3]. The modified WHO criteria for OLP diagnosis [4] proposed by Van der Meij and Van der Waal [5] are widely followed by clinicians and researchers. These criteria require the clinical appearance of relatively symmetrical bilateral white reticular lesions with histopathological signs of liquefaction degeneration of the basal epithelial cell layer, a well-defined band-like zone of lymphocytic infiltration confined to the superficial chorion, and the absence of epithelial dysplasia. Cases that fail to meet all of these criteria are designated as oral lichenoid lesions (OLLs) and in the view of the above authors [5], are attributed with a premalignant character, whereas OLPs are not [6]. Questions have been raised about epithelial dysplasia as OLP exclusion diagnostic criterion [3], given that the presence of dysplasia, especially severe dysplasia, is the gold standard for prediction of malignant transformation in OPMDs [7]. Therefore, the adoption of dysplasia as an exclusion criterion would likely select cases at lower risk of malignant transformation, with a consequent underestimation of the malignant potential of this prevalent disease [3], [8], [9], [10]. In addition, most studies to date have not provided precise information on variables that might influence malignization, such as the type of lesion, its oral localization, or habits associated with oral cancer development, e.g., tobacco and alcohol consumption. Finally, there appears to be a marked lack of knowledge about the malignant transformation potential of oral lichenoid reactions (LRs), which are clinically related to OLP and have well-established etiologies, including drug consumption or contact of the oral mucosa with dental restorative materials, mainly silver amalgam, with some authors also reporting their potential association with oral cancer [11], [12].

With this background, our objective was to qualitatively and quantitatively evaluate available scientific evidence on the malignant transformation of OLP, OLLs, and oral LRs in a systematic review and meta-analysis of 82 studies (26,742 patients) in order to precisely estimate their malignant transformation rates, explore influential variables, determine key predictive factors for progression to cancer, and identify clinical approaches to reduce the risk of malignization.

Section snippets

Material and methods

This systematic review and meta-analysis complies with PRISMA and MOOSE guidelines [13], [14], and its preparation followed criteria of the Cochrane Handbook for Systematic Reviews of Interventions [15], Centre for Reviews and Dissemination (CRD)’s guidance for undertaking reviews in health care [16], and Cochrane Prognosis Methods Group [17].

Results

The flow diagram in Fig. 1 depicts the results of the literature search and the study selection process. We retrieved 4,905 records published before November 2018: 1,109 from PubMed, 1,200 from Embase, 1,480 from Web of Science, 1,116 from Scopus, and 20 from reference lists in retrieved studies. After eliminating duplicate records, 2,353 potentially eligible studies were identified. After screening the titles and abstracts, 109 studies were selected, of which 27 did not meet all inclusion

Discussion

This systematic review and meta-analysis of 82 studies and 26,742 patients reveals reported malignant transformation rates of 1.14% for OLP, 1.88% for OLLs and 1.71% for LRs. An important conclusion of our study was that their potential for malignant transformation is likely underestimated in the literature, with most authors considering OLP, OLLs and LRs as low-risk OPMDs [107]. This may lead to their inadequate surveillance, and the resulting delay in the diagnosis of oral carcinomas arising

Acknowledgments

We would like to thank the research group CTS-392 (Plan Andaluz de Investigación, Junta de Andalucía, Spain) and Professor Miguel Delgado-Rodriguez, who made this meta-analysis possible through his support and assistance.

Declaration of Competing Interest

None declared

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