How to treat oral leucoplakia.

Abstract

Oral leucoplakia is a well-studied and relatively frequent lesion of oral mucosa that may be premalignant in nature. Leucoplakia is a strictly clinical term defined as a white patch or plaque of oral mucosa that cannot be detached or scraped off and cannot be attributed clinically or pathologically to any other disease entity. Clinically, leucoplakia can be classified into three major forms:1 (i) homogeneous (common, with a low risk of malignant transformation); (ii) speckled or nodular (rare, with a relatively high risk of malignant transformation); and (iii) proliferative verrucous (rare, with a high risk of malignant transformation). The main predisposing factors for the development of oral leucoplakia are smoking and alcohol consumption. Physical irritants, galvanism, chronic trauma, poor oral hygiene, Candida albicans and human papilloma virus (HPV) have also been incriminated. The risk of malignant transformation of leucoplakia depends on the histopathology of the lesion, specifically on the presence of epithelial dysplasia as well as the extent of dysplastic changes (mild, moderate, severe). Malignant transformation of leucoplakic lesions may also be related to the presence of HPV 16, 18 and 33, detected in 91% of our patients with leucoplakia or squamous cell carcinoma.2 The average malignant transformation rate of leucoplakia is estimated to be 5–6% or more depending on the time of observation.3 The treatment protocol of oral leucoplakia should be decided only after careful consideration of the following parameters: (i) the clinical form (homogeneous or non-homogeneous); (ii) the presence or absence of epithelial dysplasia evidenced by histopathological examination; (iii) the size of the lesion; (iv) the designation (by molecular biology) of a biological marker profile (p53, HPV 16, 18, 33); and (v) possible predisposing aetiological factors. The first step in the management of all three types of leucoplakia is in the elimination of all possible predisposing aetiological factors. If the lesion is small, excisional biopsy is recommended. It is advisable to perform incisional biopsy of larger lesions for histopathological evaluation that will guide further decisions on treatment. In addition, characterization of immunohistochemical p53 expression might have important practical consequences as it may allow early recognition and treatment of leucoplakic lesions that could progress to squamous cell carcinoma.4. Homogeneous leucoplakia with or without mild epithelial dysplasia may be reversed after stopping smoking for 2 or 3 months, particularly if it is located on the floor of the mouth. Should the lesion remain unchanged, conservative surgical excision or carbon dioxide laser surgery should be performed. More aggressive surgery is recommended for lesions that demonstrate suprabasilar p53 expression, even if no epithelial dysplasia is present. In widespread or multiple leucoplakia, oral administration of 13-cis-retinoid acid (1 mg/kg body weight daily for 2 or 3 months) may be used with usually limited results. Alternatively, topical applications of 0.05% retinoid acid solution or in the form of 0.03% Orabase creams have also been used to achieve partial remission of the lesions. In this issue, an interesting paper presents a novel topical use of acitretin in mucoadhesive slow release two-layer tablets (20 mg/day for 1 month) that appears promising for the topical treatment of selective cases of leucoplakia. However, it is important to remember that retinoic acid is potentially teratogenic in women of child-bearing age. Homogeneous leucoplakia representing moderate to severe epithelial dysplasia should always be removed either by conventional or carbon dioxide laser surgery. Speckled leucoplakia and proliferative verrucous leucoplakia should be treated with radical surgical excision, independent of the absence or degree of epithelial dysplasia, because of the high risk of malignant transformation in both forms. Other treatment modalities include cryosurgery and electrodessication, which are usually ineffective. Recurrences are relatively common in oral leucoplakia and patients should be examined periodically. Follow-up should include thorough oral clinical examination, occasional biopsy and characterization of immunohistochemical p53 expression in any suspicious lesion.