OBJECTIVES: To assess  the impact of managing women with high-risk HPV positive and Pap negative results (hrHPV+/Pap-) attending cervical cancer (CxCa) screening with a Pap and HPV test (co-testing).  The strategies tested reflect different options available if a hrHPV test versus a hrHPV including 16/18 genotyping (3-in-1 test) is used upon initial screen.  METHODS: A budget-impact model was developed, from a US payer perspective.  Data from the ATHENA (Addressing THE Need for Advanced HPV Diagnostics) trial and published literature were used to populate the model.  The scenarios tested include repeat co-testing in 12 months, reflex genotyping HPV16/18, or routine co-testing with genotyping results already available from a 3-in-1 test for triage to colposcopy. The model examined the annual cost of testing and treatment for cervical intraepithelial neoplasia grade 2 or worse (≥CIN2) and the cost of patients loss-to-follow-up. For a hypothetical population of women between ages 30 to 69, it assumes 48.5% were co-tested within the CxCa screening program every 3 years.  Of those, 6.7% of women receive hrHPV+/Pap- results.  Test performance was modeled as equivalent for both genotyping scenarios. RESULTS: In the hrHPV+/Pap- population, the cost of ≥CIN2 cases detected and treated for each testing strategy and the rate of progression to invasive CxCa per 10,000 hrHPV+/Pap- results was $10,530/9.2 (repeat co-testing at 12 months), $8,500/2.6 (reflex HPV16/18) and $7,278/2.6 (routine co-testing with 3-in-1 test). Using HPV16/18 genotyping to manage discordant co-testing results increased ≥CIN2 cases detected and prevented disease progression.  Compared to other HPV tests that require reflex genotyping, screening with a 3-in-1 test reduced the cost of follow-up by 17% annually.  CONCLUSIONS: Genotyping for HPV 16/18 improved the detection of ≥CIN2 cases over repeat co-testing in 12 months; moreover, compared to other HPV testing strategies, the 3-in-1 test reduced costs and may be a prudent screening alternative.