Multistate oral carcinogenesis-A prospective cohort study and a parallel case-control study in Taiwan.

Background: To characterize multistate oral carcinogenesis, we conducted a cohort study of patients with oral precancer and a parallel case-control study of oral cancers and controls in Taiwan.
Methods: During 2013-2019, we recruited patients with oral precancer (n = 1998) or invasive oral cancer (n = 768) and hospital-based controls (n = 717). Precancer patients were followed up biannually for up to five years; questionnaire data and biospecimens were collected at multiple timepoints. Precancer natural history (regression/persistence, incidence, progression) was evaluated through follow-up visits and linkages with Taiwan's Cancer Registry.
Cohort Updates: Cross-sectionally, 71 % of oral precancers and 62 % of cancers were attributable to betel-quid chewing, smoking, and alcohol. Precancer patients had substantially elevated risk of oral cancer (standardized-incidence-ratio vs. Taiwan general population = 14.1; 95 %CI = 12.0-16.6). Among precancer patients, 156 incident invasive oral cancers occurred (median follow-up = 6.4 years; incidence rate = 1,221/100,000 person-years; annual incidence = 1.2 %; 1-year cumulative-incidence = 1.8 %; 5-year cumulative-incidence = 6.9 %; 10-year cumulative-incidence = 9.5 %). Baseline precancer histopathology strongly predicted risk of progression to oral cancer (5-year cumulative-incidence: no-dysplasia = 5.2 %, mild-dysplasia = 7.1 %, moderate-dysplasia = 32.8 %, severe-dysplasia = 45.9 %). Most oral cancers (88.5 %) were preceded by precancers identified during the study. The study has established a resource of >63,500 biospecimens, including biopsies (n = 6,012), oral cytology (n = 18,422), oral rinses (n = 15,054), saliva (n = 15,066), and blood (n = 8,990). Ongoing investigations are characterizing oral carcinogenesis at the epidemiologic, macroscopic, microscopic, microbiomic, and genomic levels.
Conclusions: A majority of oral precancers/cancers in Taiwan are caused by betel-quid chewing, smoking, and alcohol. Patients with oral precancer have substantially elevated risk of site-concordant oral cancer. We highlight our study as a resource to collaboratively address questions regarding oral precancer/cancer natural history and clinical management.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘J. Silvio Gutkind reports consulting fees from Radionetics Oncology, BTB Therapeutics, Pangea Therapeutics, and io9 and is the founder of Kadima Pharmaceuticals, all unrelated to the current study. None of the other authors have any relevant conflicts of interest to report.’.
(Published by Elsevier Ltd.)