Objectives

Proliferative leukoplakia (PL) and localized leukoplakia (LL) are 2 distinct clinical entities associated with different malignant transformation rates. To date, little is known about the mutational landscape that might distinguish these 2 conditions. The aim of this pilot study was to genomically characterize LL and PL.

Study Design

Patients with a clinical diagnosis of oral PL and LL were enrolled in a prospective observational cohort study between December 2006 and November 2014. Sociodemographic information was collected and entered into an electronic spreadsheet. Targeted next-generation sequencing was carried out to molecularly characterize PL and LL among patients. Pearson's chi-square test was used to compare individual mutational frequencies between PL and LL. All statistical tests used a significance of P < .05 and were 2-sided.

Results

There were 17 patients with LL and 8 patients with PL; 55.6% were female and the median age was 66 years (range, 23-85). Twelve patients (47.2%) were current smokers. When comparing LL and PL cases, mutational frequencies were significantly different in a number of genes, including HLA-A and CDKN2A (PL: 37.5% vs LL: 5.9%; Bonferroni-corrected P < .05). Alterations in TP53 (PL: 37.5% vs LL: 23.5%; P = .47), KMT2D (PL: 12.5% vs LL: 5.9%; P = .57), NOTCH1 (PL: 37.5% vs LL: 17.6%; P = .28), and NFE2L2 genes (PL: 25.0% vs LL: 5.0%; P = .17) were more frequent in patients with PL than in patients with LL, although not statistically significant.

Conclusions

In this prospective pilot study we show that PL and LL have limited genomic overlap, which may explain the different clinical behaviors observed among these 2 oral conditions. Larger studies are needed to better characterize the genomic landscape of oral precancerous lesions.