Testing for high-risk human papillomavirus with genotyping for types 16 and 18 (HPV16/18) and triage by p16/Ki-67 dual-stain immunocytochemistry improves diagnostic performance in cervical cancer screening. We estimated the cost-effectiveness of HPV DNA-based primary screening strategies that detect high-risk genotypes every 5 years with either reflex cytology (hrHPV-Pap-5) or reflex dual stain (CINtec® PLUS, Roche; hereafter hrHPV-CINtec-5) versus cytology every 3 years (SoC (PAP-3)) among women aged 25-64 years, from the Chilean public healthcare perspective. A state-transition microsimulation reflected the natural history of cervical cancer in screening-eligible Chilean women, using local epidemiology and literature-informed inputs. Direct medical costs were obtained from official Chilean sources and converted to USD (1 USD = 938 CLP). Deterministic and probabilistic sensitivity analyses were conducted; a 30-64 years initiation scenario was also evaluated. Both high-risk HPV DNA-based strategies were more effective and cost-saving than SoC (PAP-3). In the 25-64 base case, hrHPV-CINtec-5 yielded the greatest health gain (13,003 incremental Quality-Adjusted Life Year, hereafter QALYs) with $16.65 saved per woman, while hrHPV-Pap-5 saved $32.57 with 12,844 QALYs. Probabilistic sensitivity analysis confirmed dominance (most simulations in the southeast quadrant) and cost-effectiveness acceptability >90% across willingness-to-pay ranges. Deterministic analysis highlighted progression risk from HPV16/18 and the discount rate as key drivers. Transitioning from PAP-3 to high-risk HPV DNA-based primary screening in Chile is projected to improve health outcomes while reducing costs. Among HPV DNA-based strategies detecting high-risk genotypes evaluated, triage with hrHPV-CINtec-5 provided the largest health gain while remaining cost-saving; hrHPV-Pap-5 maximized cost savings. These findings support modernizing the national screening program.
Copyright: © 2026 Armijo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.