Progression of Oral Leukoplakia to Cancer: Importance on Collection of Leukoplakia and Cancer Tissues from Disparate or Same Patients

Oral squamous cell carcinoma (OSCC) is a predominant type of head and neck cancer in the Indian subcontinent, mostly observed among tobacco and/or alcohol users. Oral leukoplakia (OLK) does not seriously affect patients, so it is often ignored in treatment. Some studies have reported genomic alterations and expression deregulation that drive OLK towards OSCC, conducted in two types of studies based on sample collection from (a) disparate or (b) the same patients. Demographic, tobacco/alcohol habits and biological factors may vary significantly if OLK and OSCC samples are collected from disparate patients, but they remain consistent if both tissue samples are from the same patient. Earlier, both targeted candidate gene-based and large-scale omics-based studies identified somatic mutations in TP53, CDKN2A, and PTEN, as well as broad arm-level copy number alterations and epigenetically dysregulated genes in leukoplakia and tumor tissues from disparate patients. Recent omics-based studies have identified early CASP8 somatic alterations, APOBEC mutagenesis, as well as dysregulated immune cell infiltration (decreased CD8+ T cell abundance, enrichment of pro-inflammatory immune cells) as candidate driver events for oral tumor progression from leukoplakia in the same patient. Recent single-cell transcriptomic-driven studies have also identified immune-transcriptomic features as putative driving molecular events in oral tumor development and progression. Here, we reviewed reported differences in driving gene mutations and expression deregulations in disparate and same patient settings. We also highlighted the challenges in sample collection and the opportunity of genomics and transcriptome studies for their emerging role in early diagnosis and progression.