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

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.