Malignant development of proliferative verrucous/multifocal leukoplakia: A critical systematic review, meta-analysis and proposal of diagnostic criteria.

BACKGROUND: Proliferative verrucous/multifocal leukoplakia (PVML) is an oral potentially malignant disorder (OPMD) that exhibits high rates of malignant development (MD). This study aimed to analyse the risk of MD of PVML, as well as to investigate the possible risk factors associated with its malignization. METHODS: A bibliographical search of the PubMed, Embase, Web of Science, and Scopus databases was conducted. PVML MD rates were calculated as a pooled proportion, and the risk factors were calculated as risk ratios, using fixed and random models based on the presence of heterogeneity. RESULTS: From a total of 417 records, 16 articles were retrieved for inclusion. The subgroup analysis revealed a higher MD rate in the studies that were conducted in America, and, likewise, said studies involved a longer follow-up time (>6 years). There was a non-significant lower risk of malignization among males. A negative correlation was observed between MD and the year in which the studies were published. CONCLUSIONS: The pooled MD of PVML was 65.8% (95% CI: 55.3-76.2, p < 0.001). Prospective studies of PVML must be designed using simple and universal clinical diagnostic criteria to be able to make an early diagnosis of this important OPMD and acknowledge the frequency of MD.