Dental Department, Madras Dental College Alumini Association (MDCCA), Chennai, Tamil Nadu, India
Received Date: February 22, 2017; Accepted Date: February 23, 2017; Published Date: February 25, 2017
Citation: Hannah R. Malignant Transformation of Oral Lichen Planus – Systematic Review. J. Adenocarcinoma. 2017, 2:1. DOI: 10.21767/2572-309X.100015
The aim of this systematic review is to evaluate the malignant transformation rate of oral lichen planus and to analyse the type of oral lichen planus and site in the oral cavity with maximum potential for malignant transformation.
Oral Lichen planus; Oral potentially malignant disease; Malignant transformation rate
Oral lichen planus is a common chronic inflammatory disease, seen mostly in buccal mucosa, tongue and sometimes gingiva and palate . Oral lichen planus (OLP) has a prevalence of about 0.5- 2% in the general population. It is a disease affecting the middleaged and the elderly and the female-to-male ratio is about 2:1. The diagnosis of OLP is based on a combination of characteristic clinical findings, history and histopathology .
Oral lichen planus is termed as an immunologically mediated mucocutaneous disease. The etiology and pathogenesis of OLP are unknown though several molecular hypotheses have been presented. The etiology of OLP involves the degeneration of the epithelial basal cell layer, induced by cell-mediated immunologic reactions . Clinically, OLP maybe occur in 6 clinical variants as reticular, papular, plaque-like, erosive, atrophic and bullous.  The most common are reticular and erosive forms.  Histopathologically, OLP is characterized by dense sub epithelial mph histiocytic infiltrate, increased numbers of intraepithelial lymphocytes, and degeneration of basal keratinocytes . Genital and cutaneous lichen planus are associated with approximately 20% and 15% of OLP, respectively. The most concerning fact about OLP is its potential to develop into oral squamous cell carcinoma Therefore the World Health Organization classified OLP as potentially malignant disorder in 1978 . The chronic stromal inflammation considered a possible factor driving the malignant transformation . Therefore, every patient diagnosed with OLP should be regularly monitored since malignant transformation can occur in all forms of OLP.
The World Health Organization (WHO) classifies oral lichen planus, leukoplakia and erythroplakia as potentially malignant disorders. However, the risk of progression of oral lichen planus to oral carcinoma is lower than the risk of leukoplakia and erythroplakia. Nonetheless, the malignant transformation rate of oral lichen planus and the factors that influence this rate are still questionable. According to the literature frequency of malignant transformation varies from 0 % to 12.5% . The purpose of this study was to evaluate the malignant transformation rate of oral lichen planus and the various factors affecting the malignant transformation, by a systematic review of prospective and retrospective cohort studies.
Search strategy for the identification of studies
The search strategy was in accordance with the Cochrane guidelines for systematic reviews. Articles relevant to the search strategy were identified from search data bases of PUBMED and MEDLINE till the year 2016. No timeline was included for the search. The article search included only those from the English literature. An internet search was also done to obtain the relevant articles of our interest. The title of the articles and abstracts were reviewed. The full text of selected were retrieved and further analysed (Figure 1; Table 1).
|1||Number of cases showing malignant transformation|
|2||Malignant transformation rate|
|3||Type of OLP with maximum malignant transformation potential|
|4||Site of malignant lesion|
|5||Type of malignancy associate with OLP|
Table 1: Variables of interest.
The search methodology applied in PUBMED was using the following keywords: Search (Oral lichen planus OR Lichen planus OR Oral rubber lichen planus OR Erosive lichen planus OR Atrophic lichen planus OR Bullous lichen planus OR Ulcerative lichen planus OR Oral potentially malignant disease OR PMD OR OLP OR Oral premalignant lesion OR Oral premalignant condition OR Oral potentially malignant lesion OR Oral potentially malignant condition OR OSCC OR SCC OR Squamous cell carcinoma of oral cavity OR Squamous cell carcinoma of mouth OR Oral carcinoma OR Oral cancer OR Carcinoma of oral cavity and Malignant transformation rate. In addition, an internet search was also done using the key words “Oral Lichen planus”, “Oral potentially malignant disease” and “Malignant transformation rate” (Table 2).
|#31||Search (Oral lichen planus) OR Lichen planus) OR Oral rubber lichen planus) OR Erosive lichen planus) OR Atrophic lichen planus) OR Bullous lichen planus) OR Ulcerative lichen planus) OR Oral potentially malignant disease) OR PMD) OR OLP) OR Oral premalignant lesion) OR Oral premalignant condition) OR Oral potentially malignant lesion) OR Oral potentially malignant condition) OR OSCC) OR SCC) OR Squamous cell carcinoma of oral cavity) OR Squamous cell carcinoma of mouth) OR Oral carcinoma) OR Oral cancer) OR Carcinoma of oral cavity)) AND Malignant transformation rate||304|
|#30||Search Malignant transformation rate||2155|
|#29||Search (Oral lichen planus) OR Lichen planus) OR Oral rubber lichen planus) OR Erosive lichen planus) OR Atrophic lichen planus) OR Bullous lichen planus) OR Ulcerative lichen planus) OR Oral potentially malignant disease) OR PMD) OR OLP) OR Oral premalignant lesion) OR Oral premalignant condition) OR Oral potentially malignant lesion) OR Oral potentially malignant condition) OR OSCC) OR SCC) OR Squamous cell carcinoma of oral cavity) OR Squamous cell carcinoma of mouth) OR Oral carcinoma) OR Oral cancer) OR Carcinoma of oral cavity||148096|
|#28||Search Carcinoma of oral cavity||25033|
|#27||Search Oral cancer||114324|
|#26||Search Oral carcinoma||46574|
|#25||Search Squamous cell carcinoma of mouth||16266|
|#24||Search Squamous cell carcinoma of oral cavity||18077|
|#19||Search Oral squamous cell carcinoma||25905|
|#18||Search Oral potentially malignant condition||337|
|#17||Search Oral potentially malignant lesion||205|
|#16||Search Oral premalignant condition||6900|
|#15||Search Oral premalignant lesion||1025|
|#10||Search Oral potentially malignant disease||301|
|#9||Search Ulcerative lichen planus||423|
|#8||Search Bullous lichen planus||348|
|#5||Search Reticular lichen planus||226|
|#7||Search Atrophic lichen planus||414|
|#6||Search Erosive lichen planus||777|
|#4||Search Oral rubber lichen planus||138|
|#3||Search Lichen planus||8486|
|#2||Search Oral lichen planus||3785|
Table 2: Search methodology.
Selection of studies
Inclusion criteria (Tables 3 and 4)
|Author||Year||Country||Type of study||Total cases of oral lichen planus||Number of Cases transformed to malignancy||Malignant transformation rate%||Follow up years|
|Guptaet al.||1989||India||Prospective study||344||1||0.3||3.7|
|van der meij et al.||2003||NA||Prospective study||62||0||0||2.7|
|Lanfranchi et al.||2003||Argentina||Retrospective study||719||32||4.45||NA|
|Jing Ling Xue et al.||2005||China||Retrospective study||674||4||0.6||NA|
|Laejendecker et al.||2005||Netherlands||Retrospective study||200||3||1.5||84-156 months|
|Bornstein et al. ||2006||Switzerland||Retrospective study||141||4||2.84||NA|
|Ingafou et al.||2006||UK||Prospective study||690||13||1.9||2.11|
|Hsue et al.||2007||Taiwan||Prospective study||143||3||2.1||3.7|
|Pakfetrat et al.||2009||Iran||Retrospective study||420||3||0.07||NA|
|Fang et al.||2009||China||Retrospective study||2119||23||1.1||1.4|
|Bermejo-Fenoll et al.||2010||South eastern Spain||Retrospective study||550||5||0.9||NA|
|Torrente-Castells et al.||2010||Spain||Retrospective study||65||1||1.5||0.25-212 months|
|Bombeccari et al.||2011||Italy||Prospective study||327||8||2.4||6.10|
|Zheng-Yu Shen||2012||China||Retrospective study||518||5||0.96||NA|
|Kaplan Ilana et al.||2012||Israel||Retrospective study||171||6||3.5||12-192 months|
|Budimiret al.||2014||Croatia||Retrospective study||563||4||0.7||7.6|
|Wang et al.||2014||Taiwan||Prospective study||381||2||0.52||NA|
|Casparis et al.||2015||NA||Retrospective analysis||692||8||1.2||NA|
|Iraniet al.||2016||Iran||Retrospective study||112||1||0.8||NA|
Table 3: Description of Included Studies.
|Author||Year||Type of olp with maximum malignant transformation||Type of cancer||Site ofmalignant transformation|
|van der meij et al.||2003||NA||NA||NA|
|Lanfranchi et al.||2003||17-erosive
|21-squamous cell carcinoma
|Jing Ling Xue et al.||2005||3-Erosive
|NA||3- Buccal mucosa
|Laejendecker et al. ||2005||1-Erosive
|3-Squamous cell carcinoma||2-tongue
|Bornstein et al. ||2006||NA||NA||NA|
|Ingafou et al.||2006||10 –Erosive
3 – Plaque like
|12 – Squamous cell carcinoma
1 – Carcinoma in situ
|Hsueet al.||2007||NA||3 – squamous cell carcinoma||NA|
|Pakfetrat et al.||2009||3 – erosive lichen planus||NA||2– tongue
|Bermejo-Fenoll et al.||2010||NA||5 – Squamous cell carcinoma||NA|
|Torrente-Castells et al.||2010||Red lesion||1 – Squamous cell carcinoma||1-tongue|
|Bombeccariet al.||2011||NA||8- Squamous cell carcinoma||NA|
|5- Squamous cell carcinoma||2- buccal mucosa
1- Ventral tongue
|Kaplan Ilana et al.||2012||6-Squamous cell carcinoma||4-Tongue
|Budimir et al.||2014||2-Erosive
|Wanget al.||2014||NA||NA||2- Tongue|
|Casparis et al.||2015||NA||NA||NA|
|Iraniet al.||2016||Erosive||Squamous cell carcinoma||Lateral border of tongue|
Table 4: Description of Included Studies.
A. Original studies on Malignant transformation rate of Oral Lichen Planus.
B. Retrospective and Prospective cohort studies.
C. Studies which are solely observational in nature.
D. Studies involving human participants.
E. Full length English language articles were included.
F. Studies published in peer reviewed journal.
G. All the oral lichen planus cases in the study must be proven by means of biopsy results at initial diagnosis.
Exclusion criteria (Table 5)
|Author||Year||Total cases of oral lichen planus||Number of Cases transformed to malignancy|
|Gupta et al. ||1989||344||1|
|van der meij et al. ||2003||62||0|
|Lanfranchiet al. ||2003||719||32|
|Jing Ling Xue et al. ||2005||674||4|
|Laejendecker et al. ||2005||200||3|
|Bornsteinet al. ||2006||141||4|
|Ingafouet al. ||2006||690||13|
|Hsueet al. ||2007||143||3|
|Pakfetratet al. ||2009||420||3|
|Fanget al. ||2009||2119||23|
|Bermejo-Fenoll et al. ||2010||550||5|
|Torrente-Castells et al. ||2010||65||1|
|Bombeccariet al. ||2011||327||8|
|Zheng-Yu Shen ||2012||518||5|
|Kaplan Ilana et al. ||2012||171||6|
|Budimiret al. ||2014||563||4|
|Wanget al. ||2014||381||2|
|Casparis et al. ||2015||692||8|
|Iraniet al. ||2016||112||1|
Table 5: Studies on the Number of Oral Lichen Planus Cases with Malignant Transformation. The total number of cases observed in theses 19 articles was 8891. The number of malignant transformation observed was 126.
A. Studies not done in Oral lichen planus.
B. Studies done on epithelial dysplasia
C. Case-control studies.
D. Studies in animal models were excluded.
E. Individual case studies.
Data extraction: Once the articles to be reviewed were finalized, data was extracted from each article, tabulated and was verified and interpreted.
Outcomes: The outcomes assessed in this review examined and analysed the malignant transformation rate of oral lichen planus and the various factors affecting the malignant transformation rate.
In the past, Oral Lichen Planus was a benign condition. However recently, several cases of malignancy have been reported from previously diagnosed cases of Oral Lichen Planus. Several authors have also reported malignancy to arise from unaffected sites in individuals proven with Oral Lichen Planus [8-10]. Literature underlines the following controversies: (i) Oral Lichen Planus transforms into carcinoma (ii) Oral Lichen Planus affected epithelium is more vulnerable to carcinogens (iii) carcinoma could appear in coincidence with OLP .
The putative link between Oral Lichen Planus and squamous cell carcinoma appears to be magnified due to the errors in initial diagnosis of Oral Lichen Planus. Some of the cases reporting carcinomatous changes in OLP could have been other red and white lesions with dysplastic features that mimic OLP clinically and histologically . “Lichenoid Dysplasia”, a separate entity, as explained by Eisenberg and Krutch off, represents a potentially precancerous lesion which was frequently overlooked as Oral Lichen Planus [12,13]. To avoid this confusion, ‘epithelial dysplasia’ was included as an exclusion criterion in the diagnostic criteria for Oral Lichen Planus [13,14].
The wide range of malignant transformation rates as obtained in this analysis, 0-4.45%, can be attributed to the diagnostic criteria used, mean follow-up years and the number of cases evaluated. The number of malignant cases reported was nil, despite a follow-up period of 2.7 years . Generally, higher rates of neoplasia were observed in researches with a longer period of mean follow-up period. In contrary,  in their retrospective study in 2011, reported 10 out of the 171 strictly diagnosed cases of Oral Lichen Planus, developed malignancy, yielding a high malignant transformation rate of 5.8% with a mean follow-up of 4.3 years . This result calls for an enhanced evaluation of the study population for the prevalence of risk factors or racial predilection.
The incidence of neoplasia in Oral Lichen Planus (Table 6) is observed to be slightly more in females as compared to men, in accordance with the fact that overall prevalence of Oral Lichen Planus is higher in females [1,13]. Erosive lichen is at a higher risk of carcinomatous transformation when compared to the other types, as emphasized by majority of the studies reviewed. In contrast, one retrospective study done in Switzerland, reported higher rates of malignancy in white lichen and mixed lichen respectively .
|Author||Year||Malignant transformation rate%|
|Gupta et al. ||1989||0.3|
|van der meij et al. ||2003||0|
|Lanfranchi et al. ||2003||4.45|
|Jing Ling Xue et al. ||2005||0.6|
|Laejendecker et al. ||2005||1.5|
|Bornstein et al. ||2006||2.84|
|Ingafou et al. ||2006||1.9|
|Hsueet al. ||2007||2.1|
|Pakfetrat et al. ||2009||0.07|
|Fang et al. ||2009||1.1|
|Bermejo-Fenoll et al. ||2010||0.9|
|Torrente-Castells et al. ||2010||1.5|
|Bombeccari et al. ||2011||2.4|
|Zheng-Yu Shen ||2012||0.96|
|Kaplan Ilana et al. ||2012||3.5|
|Budimir et al. ||2014||0.7|
|Wang et al. ||2014||0.52|
|Casparis et al. ||2015||1.2|
|Iraniet al. ||2016||0.8|
|S No||Year||Malignant transformation rate|
|1||1989 – 2016||126/8891 = 1.4%|
Results from the studies on malignant transformation rate of Oral Lichen Planus (1989-2016).
Table 6: Studies on the Malignant Transformation Rate.
Typically, lesions of Oral Lichen Planus were observed bilaterally, with buccal mucosa being the most common site of involvement followed by tongue [19-21]. With reference to the malignant transformation rates (Tables 7 and 8), reverse statistics have been observed; the incidence of carcinoma is reported to be higher in tongue followed by buccal mucosa.
|Author||year||Type of OLP with maximum malignant transformation|
|Lanfranchi et al. ||2003||17-erosive
|Jing Ling Xue et al. ||2005||3-Erosive
|Laejendecker et al. ||2005||1-Erosive
|Ingafou et al. ||2006||10 –Erosive
3 – Plaque like
|Pakfetrat et al. ||2009||3 – erosive lichen planus|
|Torrente-Castells et al. ||2010||Red lesion|
|Zheng-Yu Shen ||2012||4-erosive
|Budimiret al. ||2014||2-Erosive
|Irani et al. ||2016||Erosive|
Table 7: Studies on the Type of Oral Lichen Planus with Maximum Potential for Malignant Transformation. Details on the type of oral lichen planus with maximum potential for malignant transformation has been given by 9 of the articles. Of the 62 lesions mentioned, 41(66.1%) were of erosive type, 12(19.3%) keratotic, 5(8.1%) plaque like, 3(4.8%) atrophic and 1(1.6%) red lesion. Erosive lichen planus was found to be the lesion with the maximum malignant potential.
|Author||year||Type of cancer|
|Lanfranchi et al. ||2003||21-squamous cell carcinoma
|Laejendecker et al. ||2005||3-Squamous cell carcinoma|
|Ingafou et al. ||2006||12 – Squamous cell carcinoma
1 – Carcinoma in situ
|Hsue et al. ||2007||3 – squamous cell carcinoma|
|Bermejo-Fenoll et al. ||2010||5 – Squamous cell carcinoma|
|Torrente-Castells et al. ||2010||1 – Squamous cell carcinoma|
|Bombeccari et al. ||2011||8- Squamous cell carcinoma|
|Zheng-Yu Shen ||2012||5- Squamous cell carcinoma|
|Kaplan Ilana et al. ||2012||6-Squamous cell carcinoma|
|Irani et al. ||2016||Squamous cell carcinoma|
Table 8: Studies on the Malignancies Associated with Oral Lichen Planus. The type of malignancy associated with lichen planus have been enlisted by 11 articles. Out of 77 cases 65 (84.4%) were squamous cell carcinoma, 7 (9.1%) were verrucous carcinoma, 4 (5.2%) were a combination of squamous cell carcinoma and verrucous carcinoma and 1 (1.3%) was carcinoma in situ. Squamous cell carcinoma was found to be the most common malignancy associated with oral lichen planus.
The type of oral malignancy associated with oral lichen planus was found to be predominantly Squamous cell carcinoma. Nevertheless, considering the many patients with Oral Lichen Planus who present risk activities for malignant diseases of the mouth, it would seem essential that all patients with Oral Lichen Planus be informed of the potential link between Oral Lichen Planus and oral cancer .
We acknowledge that the potential presence of publication bias might have occurred within this review. The number of articles reviewed is minimal. Our search also included publications in the English literature only. No retracted articles were included. Further studies must be performed evaluating the Malignant transformation (Tables 9) of oral lichen planus in the same platform in order to generate a more homogenous and unbiased group of data. This could aid in giving better systematic reviews in future in this field of study.
|Lanfranchi et al. ||2003||16-Tongue
|Jing Ling Xue et al. ||2005||3- Buccal mucosa
|Laejendecker et al. ||2005||2-tongue
|Pakfetrat et al. ||2009||2– tongue
|Fang et al. ||2009||1-tongue|
|Torrente-Castells et al. ||2010||1-tongue|
|Zheng-Yu Shen ||2012||2- buccal mucosa
|Kaplan Ilana et al. ||2012||4-Tongue
|Wang et al. ||2014||2- Tongue|
|Irani et al. ||2016||1- tongue|
Table 9: Studies on the Site of Malignant Lesion. The site of malignancy of 53 cases have been given, of which 31 (58.4%) were found in the tongue, 18 (34%) in the buccal mucosa, 3 (5.7%) in the gngiva and 1 (1.9%) in the lip. Tongue was found to be the most common site of malignant transformation.
The total number of oral lichen planus cases in the 19 studies included were 8891. 126 of the cases turned malignant. The malignant transformation rate in individual study ranged from 0-4.45. The average malignant transformation rate was found to be 1.4%. Erosive lichen planus (66.1%) had the maximum potential for malignant transformation. The common site of occurrence of malignant transformation was the tongue (58.4%). Oral squamous cell carcinoma (84.4%) is the common malignancy associated with oral lichen planus.
The absence of strict diagnostic criteria is the culprit behind the controversy regarding the premalignant nature of OLP. Researchers should be encouraged to take up similar long term studies to estimate the Potential of oral lichen planus to turn into malignancy. Molecular and genetic analysis will provide a more explicit characterization of the potential risk. However, the outcome of this study reinforces the need for a long-term followup regimen for all cases of Oral Lichen Planus.
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