Variability and inconsistencies in the diagnosis of proliferative verrucous leukoplakia: a systematic review

Proliferative verrucous leukoplakia (PVL) is an aggressive and complex oral potentially malignant disorder, recognized for having a higher rate of malignant transformation in comparison with oral leukoplakias. Despite extensive investigation, major inconsistencies remain regarding its diagnostic criteria, clinical course, and associated features. This systematic review aimed to evaluate how PVL has been clinically and histopathologically defined, described, and reported in the literature, with emphasis on inconsistencies that may impair disease recognition and comparison across studies. A systematic search was conducted in PubMed, Embase (via Ovid), Scopus, and Web of Science. Studies of the cohort, case-control, cross-sectional, case series and case reports were included. The risk of bias was appraised using the Newcastle-Ottawa Scale and the JBI Critical Appraisal Tools. After screening 1705 studies, 47 were selected for inclusion. Among these, there were 14 observational studies (12 cohorts and 2 cross-sectionals) and 33 descriptive studies (27 case reports and 6 case series). Risk of bias appraisal showed variable methodological quality, mainly due to incomplete clinical reporting, heterogeneous follow-up, and limited control of confounding in observational studies. The current PVL literature remains limited by inconsistent diagnostic criteria, variable terminology, heterogeneous follow-up, and incomplete reporting of clinically relevant features. These limitations affect early recognition and comparison across studies. Standardized diagnostic frameworks and minimum reporting domains are needed to improve clinicopathological documentation, research reproducibility, and clinical management of PVL.