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A lack of guidance on economic evaluations for oral cancer screening programs forms a challenge for policymakers and researchers to fill the knowledge gap on their cost-effectiveness. This systematic review thus aims to compare the outcomes and design of such evaluations. A search for economic evaluations of oral cancer screening was performed on Medline, CINAHL, Cochrane, PubMed, health technology assessment databases, and EBSCO Open Dissertations. The quality of studies was appraised using QHES and the Philips Checklist. Data abstraction was based on reported outcomes and study design characteristics. Of the 362 studies identified, 28 were evaluated for eligibility. The final six studies reviewed consisted of modeling approaches (n = 4), a randomized controlled trial (n = 1), and a retrospective observational study (n = 1). Screening initiatives were mostly shown to be cost-effective compared to non-screening. However, inter-study comparisons remained ambiguous due to large variations. The observational and randomized controlled trials provided considerably accurate evidence of implementation costs and outcomes. Modeling approaches, conversely, appeared more feasible for the estimation of long-term consequences and the exploration of strategy options. The current evidence of the cost-effectiveness of oral cancer screening remains heterogeneous and inadequate to support its institutionalization. Nevertheless, evaluations incorporating modeling methods may provide a practical and robust solution. [ABSTRACT FROM AUTHOR]