Natural History of Oral Cancer Precursor Lesions

Cancers of the oral cavity (lip, oral tongue, gingiva, floor of mouth, palate, and the inner mouth lining including buccal mucosa) account for approximately 30,000 annual cases in the United States and 250,000 annual cases worldwide. While the burden of oral cancers varies geographically, incidence is highest in Asian countries. Most patients with oral cancers are diagnosed at advanced stages, undergo invasive treatments, and have poor survival. Oral cancers are believed to be preceded by precancerous lesions, defined clinically as leukoplakia (a white patch in the mouth), erythroplakia (a red patch in the mouth), and oral submucous fibrosis (irreversible fibrosis of the submucous tissue) as well as by the histopathological grade of dysplasia. Despite the ease of visual and tactile inspection of the oral cavity and recognition of precancerous lesions, there are currently no organized programs for screening and secondary prevention of oral cavity cancers in most parts of the world.

Tobacco use and alcohol consumption are the strongest risk factors for oral cancer. Whereas cigarette smoking constitutes the predominant exposure to tobacco in most parts of the world, chewing betel-quid with or without tobacco is the major exposure in the Indian subcontinent and parts of Asia. Long-term chewing of tobacco/betel-quid is associated with an approximately 50-fold increased risk of oral cancer.

Importantly, the optimal clinical management of patients with oral cancer precursor lesions is unclear due to several knowledge gaps regarding the natural history of oral cancer. In particular, the thresholds for triage and biopsy of leukoplakia are poorly-defined, the predictive value of the histopathologic presence/grade of dysplasia for the identification of precancerous lesions is reportedly equivocal, and the appropriate frequency of clinical follow-up of patients with leukoplakia for signs of early cancer is uncertain.

The NCI is conducting two studies to investigate the natural history of clinically-defined oral precursor legions to investigate the epidemiologic and molecular progression of oral cancer and guide the clinical management of patients with oral cancer precursor lesions.

Natural History of Oral Cancer Precursors in the United States

The NCI in collaboration with researchers at Kaiser Permanente Northern California (KPNC) will investigate the natural history of oral leukoplakia, the most common oral cancer precursor lesion. This retrospective cohort study aims to estimate the relative and absolute risks of progression of leukoplakia to oral cancer, the predictive accuracy of a clinician’s decision to biopsy a leukoplakia with regard to progression, and histopathologic predictors of progression. Nested molecular studies are aimed to identify molecular predictors of progression of oral leukoplakia to oral cancer.

Natural History of Oral Cancer Precursors: A Prospective Cohort Study in Taiwan

A natural history study of clinically-defined oral precancerous lesions will be conducted in collaboration with researchers at the National Taiwan University Hospital, China Medical University Hospital, and Chang Gung Memorial Hospital, to investigate the epidemiologic and molecular progression to oral cancer. The study involves collection of detailed demographic and behavioral characteristics as well as a range of biospecimens (biopsies, oral cytology, saliva, oral rinse, and blood) at multiple time points.

For more information, contact Anil Chaturvedi, Ph.D.