Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next‐generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high‐risk individuals. Noninvasive genetic screening can be employed to screen high‐risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient. What's new? Oral cancer can be revealed by detection of genetic alterations in epithelial cells of the mucosal lining. Here, the authors evaluated a sequencing assay to detect genetic changes in noninvasively collected cells. The noninvasive assay accurately identified genetic changes in oral lesions compared with biopsies, and the authors also demonstrated that their method could predict oral cancer in a cohort of Fanconi anemia patients who had no visible lesions. This approach could be useful as a screening tool for high‐risk populations or to monitor disease progression.