A pilot study to develop an efficacious oral cancer screening strategy for India Oral cancer imposes a huge burden globally, especially in low and middle income countries (LMICs) (8). This high burden of oral cancer is attributable to high prevalence of risk factors such as tobacco, areca nut (tamul) and alcohol. In most countries, cigarette smoking is the predominant form of tobacco use (9). However, in India, approximately 75% of tobacco consumption is in smokeless form (9). India has the highest burden of oral cancer globally (10). It is recognized that smokeless tobacco causes cancers of the mouth, gullet and pancreas (11). The proposed study will be conducted in Assam, where the prevalence of tobacco is 48% (12). In Assam, tamul is traditionally offered as a mark of respect and auspicious beginnings. We recently conducted a survey in Assam on tamul use. In all, 34% of subjects reported using tamul. Influencing factors were family (58%) and friends (34%). Majority of the subjects (60%) chewed tamul due to pressure at work, after food and during leisure with a mean age of initiation at 15 years. While knowledge about the ill-effects of tamul was low and willingness to quit high (77%), paradoxically, 81% of subjects had not attempted to quit the habit in the preceding 6 months.  The 5-year survival rate for oral cancer is 80% in those diagnosed at early stage and only 20% in those diagnosed at advanced stage, underscoring the need for early detection (13). In India, most oral cancer patients present with advanced disease and have survival rates as low as 3-5%. There is, therefore, a pressing need to diagnose early and ideally at a pre-cancerous stage (2).  In India and other LMICs, the current approach for oral cancer screening relies on visual inspection of the inner lining of the oral cavity (conventional oral examination [COE]) in tobacco/ alcohol users aged over 30 years (4). Yet, owing to issues with the method of screening (low sensitivity of COE) and size of the target population (ages 30+), this approach is not efficacious. For example, the eligible population for oral cancer screening in India based on COE is ~300 million, which reduces its operational feasibility and makes it cost prohibitive. Any screening system developed in LMICs should fulfill two features for optimal effectiveness: 1) The screening test should have high accuracy 2) The screening system (infrastructure, human resource and referral centres) has to be financially viable. Unfortunately, the current oral cancer screening strategy of visual inspection in India and several other LMICs fails at both these levels. Risk stratification tools for systematic identification of high-risk population could potentially drastically reduce the target population for screening.  We propose a 3-step oral cancer screening strategy to enable effective implementation of the screening program. First, a risk prediction model will be used for identification of those at greatest risk of oral cancer, thus reducing the number of screened individuals and enhancing cost effectiveness. Second, high-risk individuals will be screened using autoflourescence, a highly sensitive test for diagnosing oral cancer to rule-out disease by causing only the abnormal areas to light up. Finally, individuals positive on autofluorescence will be ruled-in through a brush biopsy to look for suspicious cells, a test that is highly specific for diagnosing oral cancer. We will validate the risk prediction model of the proposed 3-step strategy as part of this pump priming application which will subsequently lead to a large randomized controlled trial in the population of North East India to test its effectiveness. Our study will provide proof-of-principle of the 3-step screening strategy for implementation of the oral cancer screening in LMICs. The Global Challenges Research Fund (GCRF) supports cutting-edge research to address challenges faced by developing countries. The fund addresses the UN sustainable development goals. It aims to maximise the impact of research and innovation to improve lives and opportunity in the developing world.