Abstract
ABSTRACT
Objective
To synthesise biological biomarker evidence in proliferative verrucous leukoplakia/proliferative leukoplakia and quantify malignant transformation using eligible longitudinal evidence.
Methods
Primary human biomarker studies and longitudinal studies reporting extractable malignant‐transformation events and denominators were systematically reviewed. Biomarker evidence was synthesised narratively. Malignant‐transformation proportions were pooled using a random‐effects model, with conservative handling of potentially overlapping cohorts.
Results
Forty‐one publications contributed to the biomarker synthesis, spanning genetic, genomic, DNA‐ploidy, epigenetic, transcriptomic, proteomic, immunohistochemical, immunologic, viral, microbiome, salivary, and circulating markers. No biomarker had sufficient independent validation for clinical diagnostic or prognostic use. Twenty independent or conservatively non‐overlapping study estimates comprising 745 patients and 243 malignant‐transformation events contributed to the meta‐analysis. The pooled malignant‐transformation proportion was 34.13% (95% confidence interval 26.62–42.53), with substantial heterogeneity and a 95% prediction interval of 13.85%–62.56%. Results remained stable in sensitivity and leave‐one‐out analyses.
Conclusions
Diverse biological alterations have been reported, but none currently supports routine biomarker‐based diagnosis or individual risk stratification. Malignant transformation is frequent, although substantial between‐study variability limits interpretation of the pooled estimate as an individual patient risk.