In this article we compare previously published cost-effectiveness studies of human papillomavirus (HPV) vaccines along a defined subset of key model structural assumptions relating to HPV infection and disease, cervical cancer screening and HPV vaccination. For each structural aspect examined, we summarize assumptions from each study, provide a critical review and discuss the impact upon results. Considerable variation was observed across HPV vaccine cost-effectiveness models in a number of influential assumptions. Holding constant factors for which current data are lacking, the combined impact of assumptions made for the remaining parameters examined would appear to tend toward underestimation of the cost-effectiveness of HPV vaccination within existing studies. However, uncertainty concerning parameters, such as the duration of vaccine protection and acquired immunity following HPV infection, and the relationship between age and HPV virulence, complicates precise estimation of the cost-effectiveness of HPV vaccination and rigorous evaluation of the validity of existing modeling results.