key: cord-0943426-1z2o466j authors: D’Cruz, Anil K.; Vaish, Richa title: Risk-based oral cancer screening — lessons to be learnt date: 2021-04-21 journal: Nat Rev Clin Oncol DOI: 10.1038/s41571-021-00511-2 sha: e5cd7299ddaee21b32fe1b6c9e5c97b62f69a289 doc_id: 943426 cord_uid: 1z2o466j The Kerala Oral Cancer Screening Trial did not demonstrate an overall cancer-related mortality benefit. Herein, we discuss the important lessons learnt from a recent reanalysis of data from this trial in an attempt to demonstrate the advantages of using a novel risk-based approach to cancer screening. The basic premise of screening is to detect cancers early in order to improve survival, administer less-intensive treatments and decrease morbidity. The success story of screening for cervical cancers has been well established. Screening recommendations are also in place in many countries for breast, colon, lung and prostate cancers 1 . Screening has benefits but also limitations, the most important of which are its associated costs and barriers to accessibility even in the most advanced health-care systems. Now, the reanalysis of the previously published Kerala Oral Cancer Screening Trial (KOCST) provides interesting lessons to learn from 2 . Oral cancers are a global problem, with a mortality rate of ~50% 3 . Despite the ease of access to examination, these cancers present late with disastrous outcomes on survival and quality of life. Two-thirds of cancers and three-quarters of cancer-related deaths occur in Asia 3 and, thus, this region would benefit from implementing screening programmes. Prior attempts have focused on increasing detection rates of premalignant lesions and cancers using oral examination or adjuncts such as vital staining, cytology and light-based techniques 4 . To date, the KOCST is the only trial that has reduction in mortality as the end point 5 , an essential prerequisite to establish benefit from any screening programme. This randomized controlled trial consisted of three rounds of screening at 3-yearly intervals in which health-care workers performed visual oral examination. Individuals in the control group underwent health awareness education. With a mortality rate ratio of improved with targeted screening of individuals in the HRG and even further enhanced with risk-prediction model-based screening of the 50% of individuals at the highest risk, reducing the number that need to be screened to prevent one oral cancer-related death to 1,029 and 610, respectively. These findings provide proof-of-principle that risk-based screening could have substantial benefits. This approach would be particularly appropriate in resource-constrained countries with a high incidence of oral cancer, many with a lack of basic infrastructure and existing screening programmes. Scarce resources could then be judiciously used targeting individuals most likely to benefit. Even in high-income countries, where oral cancer screening is not accorded high priority owing to its low prevalence, this approach would be conceptually attractive. Some concerns remain, however. Individuals in the HRG, prone to substance abuse, are the least likely to comply with screening. Indeed, only 20% of eligible population completed the planned screening visits in the KOCST 8 , a high literacy rate (>90%) notwithstanding 9 . In addition, nearly one-third of cancers diagnosed in the intervention arm were detected as interval cancers 6 . Owing to the high incidence of interval cancers, this biologically aggressive cancer should logically be screened more frequently than every 3 years. Such shorter intervals would additionally erode the number of individuals that undergo screening and also increase costs incurred. Furthermore, in contrast to cervical cancers, oral cancers do not have as welldefined a tumour progression model. Not all cancers can be traced back to arise from premalignant lesions, and only 5% of such lesions progress to cancer. In the absence of proven molecular tests to identify high-risk premalignant lesions, many asymptomatic individuals would undergo unwanted procedures, placing additional burden on the health-care system as well as subjecting individuals to unnecessary anxiety and morbidity. These concerns suggest that the inclusion of routine oral cancer screening will not 0.79 (95% CI 0.51-1.22), the difference was not statistically significant across the entire cohort; however, a statistically significant reduction was observed in the high-risk group (HRG), comprising ever tobacco and/or alcohol users, with a mortality rate ratio of 0.66 (95% CI 0.45-0.95) 6 . Screening was performed at