OBJECTIVES: To compare both economic and clinical impact of alternative cervical cancer (CC) screening strategies for women 25-65 years old using different algorithms with primary screening methods including cytology alone or hrHPV test and genotyping METHODS: Screening and diagnosis of CC were modeled by a decision tree while the natural history of the disease was simulated by a Markov model using published available data. The compared strategies were: 1) triennially hrHPV testing with 16/18 genotyping and reflex cytology 2) triennially HPV testing with reflex genotyping and reflex cytology and 3) annually cytology alone. Clinical inputs were derived from the HERMES local trial. Unit costs for the resources used were obtained from the official price lists while the HPV test cost was based on the private’s sector prices. In the absence of relevant data, the cost of treating cervical intraepithelial neoplasia (CIN2+) and invasive CC was based on the respective Spanish costs which were converted to 2014 Greek values using the relevant Consumer Price Index and Purchasing Power Parity exchange rate. RESULTS: Strategy 1 was proved to be the dominant option as it was estimated to be less costly and more effective. In more detail, cytology alone detected 58% and 52% of CC and CIN2+ cases, respectively while strategies 1 and 2 managed to detect 94% and 85% of CC and CIN2+cases,respectively. In terms, of CCs missed, strategy 3 appears to miss 24 incidents annually in contrast to 18 of strategies 1 and 2. The annual cost of strategy 1 was estimated at €14,568,412 compared to the cost of strategy 2 and 3 which was estimated at € 38,109,522 and €18,209,511, respectively. CONCLUSIONS: The adoption of hrHPV test with 16/18 genotyping as a primary screening method can generate significant savings to the Greek health care system and in parallel optimize health outcomes.