Background: Oral leukoplakia is a relatively common oral lesion that in a small but significant proportion of cases changes into cancer. Since most leukoplakias are asymptomatic, the primary objective of treatment should be to prevent such malignant transformation.
Objectives: To assess effectiveness, safety and acceptability of treatments for leukoplakia.
Search strategy: The following databases were searched for relevant trials: Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE. Handsearching was performed for the main oral medicine journals. References of included studies and reviews were checked. Oral medicine experts were contacted through an European mailing list (EURORALMED).
Selection criteria: Randomised controlled trials (RCTs), enrolling patients with a diagnosis of oral leukoplakia, were included. Any surgical or medical (topical and systemic) treatment was included. The primary outcome considered was malignant transformation of leukoplakia. Other outcomes considered were clinical resolution, histological modification and frequency of adverse effects.
Data collection and analysis: Data were collected using a specific extraction form. Malignant transformation of leukoplakia, demonstrated by histopathological examination, was the main outcome considered. Secondary outcomes included clinical resolution of the lesion and variation in dysplasia severity. The validity of included studies 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. When valid and relevant data were collected, a meta-analysis of the data was undertaken.
Main results: The possible effectiveness of surgical interventions, including laser therapy and cryotherapy, has never been studied by means of a RCT. Nineteen potentially eligible RCTs of non-surgical interventions were identified: eight were excluded for different reasons, four were ongoing studies, leaving seven studies to be included in the review. Two studies resulted at low risk of bias, four at moderate risk of bias and one at high risk of bias. Vitamin A and retinoids were tested by five RCTs (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 when compared with the 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; however, interventions were well accepted by patients, since drop-out rates were similar between treatment and control groups.
Reviewers' conclusions: To date there is no evidence of effective treatment in preventing malignant transformation of leukoplakia. Treatments may be effective in the resolution of lesion, however relapses and adverse effects are common.