Clinical and lifetime natural history of oral cancer: implications for screening and surveillance

Abstract

Abstract Background We estimated the clinical and lifetime natural history of oral cancer to inform empirical screening and surveillance algorithms. Methods We used data from ever-chewers/smokers/alcohol drinkers in the screening arm of the Kerala Oral Cancer Screening Trial (1996-2010), who attended at least one screen (n = 41,225) or two consecutive screens (n = 28,821). The clinical natural history (sensitivity, positive predictive value [PPV] and complement of negative predictive value [cNPV]) was estimated using Kaplan-Meier methods. The multistate natural history across initiation of chewing/smoking/drinking, precancer, early-stage cancer, late-stage cancer, and competing mortality was estimated using semi-Markov models. Results Visual-inspection over 2 consecutive screens (median=3.5 years apart [IQR=2.9-3.9]) had sensitivity=89.2%, PPV=1.55%, and NPV=99.96% for prevalent oral cancers (n = 83). On the first screen, 10.0% were positive with a referable oral lesion/precancer, and 12.9% were positive on either screen. Screen-positivity on both screens provided 32-fold risk-stratification for incident cancers over 11 years of follow-up (PPV=4.13% vs. cNPV in persistent screen-negatives=0.13%). Screen-positives on either screen accounted for 66.1% of incident oral cancers through 11 years of follow-up. In the lifetime/multistate model, an estimated mean=18.2% of ever-smokers/chewers/drinkers would develop oral precancer and mean=6.04% would progress from precancer to early-stage cancer (mean sojourn=19.3 years). The estimated mean sojourn time from early-stage to late-stage oral cancer was 2.7 years. Conclusions Oral cancer screening intervals could be extended to 10 years for repeat negatives on 2 consecutive screens. The high PPV and short sojourn time from early-stage to late-stage cancer indicate the need for intensive surveillance among screen-positives with precancer. Clinicaltrials.gov identifier NCT04494620.