OBJECTIVES: To determine the cost-effectiveness of various cervical cancer (CxCa) screening algorithms including the cobas HPV Test in Mexico, which identifies HPV genotypes 16/18 individually while simultaneously detecting the other high-risk HPV types. METHODS: A cohort Markov model was developed to compare five CxCa screening strategies: (S1) cytology only, (S2) cytology with reflex HPV; (S3) HPV with reflex cytology, and (S4) cytology and HPV co-testing; (S5) cobas HPV with genotyping and reflex cytology.   Screening began at age 30 with a routine screening interval of every 3 years, and was modeled over a time horizon of 40 years. Performance of the overall screening strategies was derived from the ATHENA (Addressing THE Need for Advanced HPV Diagnostics) trial. Trial baseline data were used for the base case, and 1-year follow-up outcomes were estimated for the alternative scenario, assuming all persistent disease is detected in the subsequent visit. The direct costs for screening and treatment of CxCa were estimated using the perspective of Mexican Institute of Social Security (IMSS). Costs were in 2010 US dollars.  Costs and quality-adjusted life years (QALYs) were discounted at 3% annually.  One-way sensitivity analyses were conducted.  RESULTS: Using a $20,000/QALY threshold, baseline screening with S5 dominated S3 and S4 by reducing overall cost, annual cancer incidence, and improving QALYs; and was cost-effective compared to S1 and S2.  In the 1-year follow-up scenario, S5 was cost-effective compared to all other strategies.  Detection of HPV 16/18 with S5 resulted in earlier diagnosis of clinically relevant CIN 2/3 at the initial visit as well as more efficient use of screening tests during follow-up. Sensitivity analyses showed that test sensitivities were the most impactful on model results.     CONCLUSIONS: Incorporating the cobas HPV test with HPV 16/18 genotyping was cost-effective compared to various CxCa screening strategies, and resulted in improved protection against CxCa.