Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: a follow-up study in an Italian population

doi:10.1016/S1368-8375(03)00139-8

Oral Oncology

Volume 40, Issue 1, January 2004, Pages 77-83

https://doi.org/10.1016/S1368-8375(03)00139-8 Get rights and content

Abstract

The most important complication of oral lichen planus (OLP) is the development of oral squamous cell carcinoma (OSCC) but this is a very controversial matter. The aim of the study was to estimate in a Northern Italian cohort of OLP patients the risk for OSCC. Four hundred and two patients with histologically confirmed OLP diagnosed from January 1988 to July 1999, were followed-up to the end of February 2001. The standardized incidence ratio (SIR) of OSCC was calculated for the entire cohort and specific for gender, type of OLP, therapy for OLP and hepatitis C virus (HCV) infection. The relative risk (RR) of OSCC according to HCV infection was also estimated in the cohort. During the follow-up period, two men (1.3%) and seven women (2.9%) developed an OSCC. The SIR was 44.9 (95% CI: 20.5–85.2), being higher among women, but statistically significant in both genders. The RR of OSCC for patients with HCV as compared with those without HCV infection was 3.16 (0.8–12.5). Patients with OLP had a significantly increased risk of OSCC, irrespective of the clinical type of OLP and therapy. HCV infection apparently increased the risk for OSCC although this result could reflect the role of confounders, such as liver cirrhosis.

Introduction

The most important complication of oral lichen planus (OLP) is the development of an oral squamous cell carcinoma, although this is a very controversial matter.¹ Results from previous studies show a large heterogeneity and the estimates of the frequency of malignant evolution vary between 0% and 12.5%.2, 3, 4 Meta-analysis of published data is difficult because of differences in diagnostic criteria, time of follow-up and information on exposure to known oral carcinogens. The diagnostic criteria are a major problem as there is not an accepted standard.⁴ Thus, results from some studies are biased by the inclusion of OLPs with histological signs of epithelial dysplasia with lichenoid appearance (lichenoid dysplasias), which is a well established premalignant entity.⁵ The lack of well-defined objective criteria of epithelial dysplasia, mainly when there is abundant inflammation, also adds inconsistency between studies.¹

Results of studies conducted in the 1980s onwards however report more consistent estimates, suggesting that OLP may be a premalignant condition.3, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 Nevertheless, according to a recent review,⁴ the available evidence is not yet sufficient to reach a conclusion. Moreover, only minimal loss of heterozygosis in OLP lesions has been found, suggesting that OLP is not a lesion inherently at risk for malignant trasformation.¹⁷ On the other hand a significant alteration in the expression of p53 and c-erbB-2 has been found by two independent studies that analyzed cases of OLP evolving toward oral cancer.18, 19

The association between OLP and the hepatitis C virus (HCV) is also controversial. An increased prevalence of HCV infection in patients with OLP has been described, mainly in southern Europe and Japan,²⁰ and oral verrucous and squamous cell carcinomas have been reported in HCV-infected patients.3, 21, 22, 23 HCV infection may thus increase the risk of oral cancer among OLP patients who could be already at high risk.

The aim of our study is to estimate the risk for oral cancer in a northern Italian cohort of patients diagnosed with OLP by the use of strict diagnostic criteria. The role in OLP transformation of HCV infection and other factors, such as clinical form of OLP, are also investigated.

Section snippets

Subjects and methods

Patients diagnosed with OLP at the Oral Medicine section of the Department of Biomedical Science and Human Oncology of the main hospital of the city of Turin, Italy, from January 1988 to July 1999 were selected for the present study. According to Krutchkoff,² the diagnosis of OLP was based on the following criteria:

A.
Presence of characteristic bilateral clinical signs of OLP [papular and/or reticular lesions (Wickham striae) alone or in association with atrophic or erosive lesions];
B.
Histologic

Results

The cohort included 402 patients with OLP, who were followed-up for 4.9 years on average. Main characteristics of subjects at the time of enrolment in the cohort are summarized in Table 1. Most of the patients were non-smokers (72.8%) and 19.3% were HCV infected. The red form of OLP was more frequent than the white one among both genders.

During the follow-up period two men (1.3%) and seven women (2.9%) developed an oral squamous cell carcinoma. The clinical features of the tumors and some

Discussion

There are two critical variables for the estimate of malignant development of OLP: the original diagnosis of OLP and the time from diagnosis to malignant development. The diagnosis of OLP is based on the contemporaneous presence of several clinical and histopathological criteria, but it still relies on a important amount of subjectivity.¹ Thus, some previous findings could have been distorted by the inclusion of dysplastic lichenoid lesions that are well established premalignant entities.⁵

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Risk of oral squamous cell carcinoma in 402 patients with oral lichen planus: a follow-up study in an Italian population

Abstract

Introduction

Section snippets

Subjects and methods

Results

Discussion

Oral Surg. Oral Med. Oral Pathol.

Oral Surg. Oral Med. Oral Pathol.

Oral Surg, Oral Med, Oral Pathol.

Oral Oncol

Eur J Surg Oncol

Oral Oncol

Oral Oncol

J Am Acad Dermatol

Malignant transformation in oral lichen planus Int J Oral Surg

J Hepatol

Management of oral lichen planus

Am J Clin Dermatol

Oral lichen planusthe evidence regarding potential malignant transformation

J. Oral Pathol.

The possible association between oral lichen planus and oral squamous cell carcinomaa clinical evalutation on 14 cases and a review of the literature

Oral Oncol.

A review of the recent literature regarding malignant trasformation of oral lichen planus

Oral Surg, Oral Med, Oral Pathol, Oral Radiol Endod

Malignant potential of oral lichen planusobservations in 722 patients from India

J. Oral Pathol.

Malignant development of lichen planus-affected oral mucosa

J Oral Pathol

Oral lichen planus among 4277 patients from Gizan

Saudi Arabia Community Dent Oral Epidemiol

Possible premalignant character of oral lichen planus. The Amsterdam experience

J. Oral Pathol. Med.

Oral cancer development in patients with oral lichen planus

J. Oral Pathol. Med.