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OBJECTIVES: To investigate the available evidence on the malignant transformation (MT) of oral proliferative verrucous leukoplakia (PVL). MATERIAL AND METHODS: We searched six main electronic and three grey literature databases in a two-phase process. Cohort studies investigating MT of PVL were eligible for inclusion. The risk of bias (RoB) was assessed using a specific tool developed by the Joanna Briggs Institute. Proportion meta-analyses were performed using a random-effects model. RESULTS: Study selection resulted in the inclusion of 17 studies. The pooled proportion of MT was 43.87% (95% CI = 31.93-56.13). Females (64.02%, 95% CI = 54.87-72.75) were more affected by PVL than males (35.98%, 95% CI = 27.25-45.13). Gingiva (39.6%) and buccal mucosa (21.6%) were the most frequent PVL sites. No conclusive results were found between MT and sex or age distribution, tobacco, or alcohol consumption. Gingiva was the most common site for MT (39.9%), and the most frequent histopathological subtype was conventional squamous cell carcinoma (62.1%). Four studies were classified as low, nine as moderate, and four as high RoB. CONCLUSION: The MT pooled proportion was 43.87%. Among OPMDs, PVL has the highest risk to transform to malignancy. Development and agreement on diagnostic criteria for PVL would reduce the heterogeneity among future studies.

Objectives To explore the pathophysiology of proliferative verrucous leukoplakia, a rare oral disorder that exhibits high rates of recurrence and malignant transformation, through a RNAseq case-control study. Material and methods We obtained oral biopsies from 10 patients with verrucous leukoplakia lesions and from the mucosa of 5 healthy individuals for sequencing using RNAseq technology. Using bioinformatic methods, we investigated gene expression and enrichment differences between patients both with and without the disorder. We applied network biology methods to investigate functional relations among those genes that were differentially deregulated. Results We detected 140 differentially expressed genes with distinct roles in immune surveillance, tissue and organ morphogenesis, development, and organization. Of these 140 genes, 111 have been previously described as cancer expression biomarkers, being oral squamous cell carcinoma the most represented type of cancer among them. Of these 140 genes, 26 were prioritized for further investigation as biomarkers using larger sample sizes. Conclusions The gene expression patterns of healthy and unhealthy patients differed in 140 genes whose deregulation has a functional impact on normal functioning of the immune system. This immune expression profile provides a plausible hypothesis to explain the transformation to oral squamous cell carcinoma observed in 6 of the 10 assayed cases.

Cytokines and chemokines have been analysed in patients with oral squamous cell carcinoma and potentially malignant disorders. We selected interleukin-6 (IL-6) because it is a multifunctional interleukin reported to be altered in potentially malignant oral disorders and in malignant lesions. To date, this has not been evaluated or tested in proliferative verrucous leukoplakia (PVL), however.