Objectives: The aim of this study was to summarize the current evidence for the cost-effectiveness of primarily human papillomavirus (HPV) -based cervical cancer screening in settings with already established Papanicolaou test (Pap) programs. Emphasis was placed on the German situation with annual Pap screening. Methods: Medical, economic, and health technology assessment (HTA) databases were systematically searched for cost-effectiveness studies comparing HPV to Pap screening. Study data were extracted, standardized, and summarized in cost-effectiveness plots contrasting HPV strategies to Pap screening with 1-, 2-, 3-, and 5-years interval. For each Pap setting, the likelihood of cost-effective HPV screening was assessed depending on willingness-to-pay. Results: We reviewed twelve decision-analytic cost-effectiveness models. Study results showed wide variation due to methodical heterogeneity. Data synthesis revealed that the cost-effectiveness of HPV screening depends on the interval of the established Pap screening strategy. In comparison with Pap screening every 2 years, only 25 percent of the HPV-based screening strategies were cost-effective. However, in comparison with Pap screening every 1, 3, or 5 years, 83 percent, 55 percent, and 92 percent of HPV screening strategies were cost-effective, respectively. Results for settings with annual Pap screening are based on models assuming 100 percent screening coverage. Conclusions: The introduction of HPV-based screening programs is cost-effective if the screening interval of the established Pap program exceeds 2 years. In settings with biennial Pap screening, introduction of HPV-based screening is unlikely to be cost-effective. Results also suggest cost-effectiveness of HPV-based screening in settings with annual Pap screening; however, this finding should be confirmed under realistic screening adherence assumptions. © 2008 Cambridge University Press.