Oral Leukoplakia: Genetic Changes and Malignant Transformation

Oral leukoplakia, the most common potentially malignant oral disorder, has an estimated worldwide prevalence of 1% and annual malignant transformation rate of 2%. Several factors responsible for an increased risk of malignant transformation of oral leukoplakia have been identified such as gender, age, smoking habits, alcohol consumption, homogeneity, size, location, degree of epithelial dysplasia and HPV-infection. Oral epithelial dysplasia grading is currently recognized as the most useful prognostic indicator for predicting conversion of potentially malignant disorders of the oral cavity to squamous cell carcinoma, although the diagnosis of oral epithelial dysplasia is subjective and thus sometimes unreliable. However, it is the only tool used as a basis for deciding management options. There is currently no consensus whether treatment of leukoplakia prevents oral cancer development. Since patients may develop new leukoplakias or primary tumors at different locations in the oral cavity, all patients remain under surveillance to increase chances for early detection of malignant progression. Biomarkers and genetic changes have been identified and show promising results in identifying which potential malignant disorders are at risk of malignant progression. We set up a noninvasive methodology to detect genetic changes in leukoplakia using a next generation sequencing approach. Biopsies and oral brush samples from a prospective cohort of leukoplakia patients were subjected to low-coverage whole-genome sequencing for the detection of large copy number aberrations and deep target-enriched sequencing for the detection of mutations in genes that are commonly mutated in head and neck cancer. Follow-up of this cohort may give information whether detection of genetic changes can predict which leukoplakias are at increased risk of malignant progression.