Malignant Transformation of Oral Lichen Planus – Systematic Review

Hannah R*

Dental Department, Madras Dental College Alumini Association (MDCCA), Chennai, Tamil Nadu, India

*Corresponding Author:
Hannah R
Member of Madras Dental College Alumini Association (MDCCA), Moorthy Nagar
Chettiar Agaram, Thiruverkadu Post, Chennai-600 077, Tamil Nadu, India.
Tel: +914425340441
E-mail: [email protected]

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

 
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Abstract

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.

Keywords

Oral Lichen planus; Oral potentially malignant disease; Malignant transformation rate

Background

Oral lichen planus is a common chronic inflammatory disease, seen mostly in buccal mucosa, tongue and sometimes gingiva and palate [1]. 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 [2].

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 [3]. Clinically, OLP maybe occur in 6 clinical variants as reticular, papular, plaque-like, erosive, atrophic and bullous. [4] The most common are reticular and erosive forms. [5] Histopathologically, OLP is characterized by dense sub epithelial mph histiocytic infiltrate, increased numbers of intraepithelial lymphocytes, and degeneration of basal keratinocytes [4]. 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 [6]. The chronic stromal inflammation considered a possible factor driving the malignant transformation [7]. 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% [6]. 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.

Methods

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).

S No Variables
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.

adenocarcinoma-Search-strategy

Figure 1: Search strategy for the identification of studies.

Search methodology

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).

Search Query Items found
#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
#21 Search SCC 16613
#20 Search OSCC 4223
#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
#14 Search OLP 1264
#11 Search PMD 1746
#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.[15] 1989 India Prospective study 344 1 0.3 3.7
van der meij et al.[14] 2003 NA Prospective study 62 0 0 2.7
Lanfranchi et al.[19] 2003 Argentina Retrospective study 719 32 4.45 NA
Jing Ling Xue et al.[18] 2005 China Retrospective study 674 4 0.6 NA
Laejendecker et al.[2] 2005 Netherlands Retrospective study 200 3 1.5 84-156 months
Bornstein et al. [20] 2006 Switzerland Retrospective study 141 4 2.84 NA
Ingafou et al.[23] 2006 UK Prospective study 690 13 1.9 2.11
Hsue et al.[21] 2007 Taiwan Prospective study 143 3 2.1 3.7
Pakfetrat et al.[24] 2009 Iran Retrospective study 420 3 0.07 NA
Fang et al.[22] 2009 China Retrospective study 2119 23 1.1 1.4
Bermejo-Fenoll et al.[25] 2010 South eastern Spain Retrospective study 550 5 0.9 NA
Torrente-Castells et al.[26] 2010 Spain Retrospective study 65 1 1.5 0.25-212 months
Bombeccari et al.[27] 2011 Italy Prospective study 327 8 2.4 6.10
Zheng-Yu Shen[17] 2012 China Retrospective study 518 5 0.96 NA
Kaplan Ilana et al.[16] 2012 Israel Retrospective study 171 6 3.5 12-192 months
Budimiret al.[7] 2014 Croatia Retrospective study 563 4 0.7 7.6
Wang et al.[28] 2014 Taiwan Prospective study 381 2 0.52 NA
Casparis et al.[24] 2015 NA Retrospective analysis 692 8 1.2 NA
Iraniet al.[8] 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
Guptaet al.[15] 1989 NA NA NA
van der meij et al.[14] 2003 NA NA NA
Lanfranchi et al.[19] 2003 17-erosive
11- Keratotic
21-squamous cell carcinoma
7-verrucuos carcinoma
4-both
16-Tongue
11-Buccal mucosa
Jing Ling Xue et al.[18] 2005 3-Erosive
1-Atrophic
NA 3- Buccal mucosa
1-Tongue
Laejendecker et al. [2] 2005 1-Erosive
1-Hyperkeratotic
1-Atrophic
3-Squamous cell carcinoma 2-tongue
1-buccal mucosa
Bornstein et al. [20] 2006 NA NA NA
Ingafou et al.[23] 2006 10 –Erosive
3 – Plaque like
12 – Squamous cell carcinoma
1 – Carcinoma in situ
NA
Hsueet al.[21] 2007 NA 3 – squamous cell carcinoma NA
Pakfetrat et al.[24] 2009 3 – erosive lichen planus NA 2– tongue
1-Buccal mucosa
Fanget al.[22] 2009 NA NA tongue
Bermejo-Fenoll et al.[26] 2010 NA 5 – Squamous cell carcinoma NA
Torrente-Castells et al.[26] 2010 Red lesion 1 – Squamous cell carcinoma 1-tongue
Bombeccariet al.[27] 2011 NA 8- Squamous cell carcinoma NA
Zheng-Yu Shen[17] 2012 4-erosive
1-plaque like
5- Squamous cell carcinoma 2- buccal mucosa
1- Ventral tongue
1-Gingiva
1- Lip
Kaplan Ilana et al.[16] 2012   6-Squamous cell carcinoma 4-Tongue
2-gingiva
Budimir et al.[7] 2014 2-Erosive
1-Atrophic
1-Plaque like
NA NA
Wanget al.[28] 2014 NA NA 2- Tongue
Casparis et al.[29] 2015 NA NA NA
Iraniet al.[8] 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. [15] 1989 344 1
van der meij et al. [14] 2003 62 0
Lanfranchiet al. [19] 2003 719 32
Jing Ling Xue et al. [18] 2005 674 4
Laejendecker et al. [2] 2005 200 3
Bornsteinet al. [20] 2006 141 4
Ingafouet al. [23] 2006 690 13
Hsueet al. [21] 2007 143 3
Pakfetratet al. [24] 2009 420 3
Fanget al. [22] 2009 2119 23
 Bermejo-Fenoll et al. [25] 2010 550 5
Torrente-Castells et al. [26] 2010 65 1
Bombeccariet al. [27] 2011 327 8
Zheng-Yu Shen [17] 2012 518 5
Kaplan Ilana et al. [16] 2012 171 6
Budimiret al. [7] 2014 563 4
Wanget al. [28] 2014 381 2
Casparis et al. [24] 2015 692 8
Iraniet al. [8] 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.

Discussion

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 [11].

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 [12]. “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 [15]. Generally, higher rates of neoplasia were observed in researches with a longer period of mean follow-up period. In contrary, [16] 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 [17]. 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 [18].

Author Year Malignant transformation rate%
Gupta et al. [15] 1989 0.3
van der meij et al. [14] 2003 0
Lanfranchi et al. [19] 2003 4.45
Jing Ling Xue et al. [18] 2005 0.6
Laejendecker et al. [2] 2005 1.5
Bornstein et al. [20] 2006 2.84
Ingafou et al. [23] 2006 1.9
Hsueet al. [21] 2007 2.1
Pakfetrat et al. [24] 2009 0.07
Fang et al. [22] 2009 1.1
Bermejo-Fenoll et al. [25] 2010 0.9
Torrente-Castells et al. [26] 2010 1.5
Bombeccari et al. [27] 2011 2.4
Zheng-Yu Shen [17] 2012 0.96
Kaplan Ilana et al. [16] 2012 3.5
Budimir et al. [7] 2014 0.7
Wang et al. [28] 2014 0.52
Casparis et al. [24] 2015 1.2
Iraniet al. [8] 2016 0.8
S No Year Malignant transformation rate
1 1989 – 2016 126/8891 = 1.4%

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. [19] 2003 17-erosive
11- Keratotic
Jing Ling Xue et al. [18] 2005 3-Erosive
1-Atrophic
Laejendecker et al. [2] 2005 1-Erosive
1-keratotic
1-Atrophic
Ingafou et al. [23] 2006 10 –Erosive
3 – Plaque like
Pakfetrat et al. [24] 2009 3 – erosive lichen planus
Torrente-Castells et al. [26] 2010 Red lesion
Zheng-Yu Shen [17] 2012 4-erosive
1-plaque like
Budimiret al. [7] 2014 2-Erosive
1-Atrophic
1-Plaque like
Irani et al. [8] 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. [19] 2003 21-squamous cell carcinoma
7-verrucuos carcinoma
4-both
Laejendecker et al. [2] 2005 3-Squamous cell carcinoma
Ingafou et al. [23] 2006 12 – Squamous cell carcinoma
1 – Carcinoma in situ
Hsue et al. [21] 2007 3 – squamous cell carcinoma
Bermejo-Fenoll et al. [26] 2010 5 – Squamous cell carcinoma
Torrente-Castells et al. [26] 2010 1 – Squamous cell carcinoma
Bombeccari et al. [27] 2011 8- Squamous cell carcinoma
Zheng-Yu Shen [17] 2012 5- Squamous cell carcinoma
Kaplan Ilana et al. [16] 2012 6-Squamous cell carcinoma
Irani et al. [8] 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 [22].

Limitations of the Review

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.

Author year Site
Lanfranchi et al. [19] 2003 16-Tongue
11-Buccal mucosa
Jing Ling Xue et al. [18] 2005 3- Buccal mucosa
1-Tongue
Laejendecker et al. [2] 2005 2-tongue
1-buccal mucosa
Pakfetrat et al. [24] 2009 2– tongue
1-Buccal mucosa
Fang et al. [22] 2009 1-tongue
Torrente-Castells et al. [26] 2010 1-tongue
Zheng-Yu Shen [17] 2012 2- buccal mucosa
1- tongue
1-Gingiva
1- Lip
Kaplan Ilana et al. [16] 2012 4-Tongue
2-gingiva
Wang et al. [28] 2014 2- Tongue
Irani et al. [8] 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.

Conclusion

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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