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Whole Disease Models (WDMs) are decision analytic models characterized by their ability to reflect the policy changes that occur at multiple points within the entire clinical trajectory of a given disease. They differ from conventional ‘piecewise’modeling approaches in their ability to reflect processes that occur ‘upstream’and ‘downstream’from a technology decision of interest. This dissertation describes the development of a WDM of oral cancer, and its application in generating evidence to inform Health Technology Management (HTM). The dissertation reviews the available scientific literature concerning health economic decision analytic modeling in oral cancer, and argues that a Whole Disease Model approach is appropriate for economic evaluation in this disease. A conventional piecewise Markov model is used to evaluate the cost-effectiveness of risk-guided management of oral premalignancy, and the limitations of that approach are discussed. The dissertation then describes the development and validation of the Whole Disease Model of Oral Cancer (WDMOC). The WDMOC is used to re-evaluate the risk-guided management policy, and how the cost-effectiveness of such a policy is influenced by upstream (tobacco/alcohol cessation, improved screening) and downstream (improved surgical treatment for early-stage disease, improved systemic therapy for late-stage disease) policy changes, including the hypothetical effect of a population HPV vaccination program. The WDMOC found that risk-guided management was cost saving compared to current standard practice, but was not expected to produce gains in quality-adjusted life years …