Although leukoplakia responds to some treatments relapses and adverse effects are common

The Cochrane Oral Health Group's Trials Register, Cochrane Central Trials Register, Medline and Embase were searched, as well as the following journals: Cancer, Community Dentistry and Oral Epidemiology, European Journal of Oral Sciences, Journal of Dental Research, Oral Oncology, Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics. The reference lists of included studies and reviews were checked, and oral medicine experts were contacted through a European mailing list (EURORALMED).

Randomised controlled trials (RCT) were included if they had enrolled patients who had a diagnosis of oral leukoplakia and who were undergoing any surgical or medical (topical and systemic) treatment. The primary outcome considered was malignant transformation of leukoplakia demonstrated by histopathological examination. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects.

Data were collected using a specific extraction form. The validity of studies included was assessed by two reviewers, on the basis of the method of allocation concealment, blindness of the study and loss of participants. Data were analysed by calculating relative risk (RR). When valid and relevant data were collected, a meta-analysis of the data was undertaken.

The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of an RCT. Nineteen RCT of nonsurgical interventions were identified: seven were included. Vitamin A and retinoids were tested in five RCT (245 patients); the other drugs tested were bleomycin (one study), mixed tea (one study) and beta-carotene (one study). Malignant transformation was recorded in just two studies. None of the treatments tested showed a benefit compared with placebo. Treatment with beta-carotene and vitamin A or retinoids was associated with significant rates of clinical resolution, compared with placebo or absence of treatment. Whenever reported, a high rate of relapse was a common finding. Side effects of variable severity were often described but interventions were well accepted by patients, since dropout rates were similar between treatment and control.

To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesions, but relapses and adverse effects are common.