<p>Model Input Base Case Values.</p>

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.针对16、18型（HPV16/18）基因分型的高危型人乳头瘤病毒（high-risk human papillomavirus, hrHPV）检测，联合p16/Ki-67双染色免疫细胞化学法进行分流，可提升宫颈癌筛查的诊断效能。本研究从智利公共医疗体系视角出发，针对25~64岁女性群体，对比了以高危型HPV DNA检测为基础的两类初筛策略——每5年检测一次高危基因型，分别辅以反射式细胞学检查（hrHPV–Pap-5）或反射式双染色检测（CINtec® PLUS，罗氏；以下简称hrHPV–CINtec-5），与每3年一次的细胞学筛查（标准护理方案，SoC (PAP-3)）的成本效益。研究采用状态转移微观模拟模型，结合智利本地流行病学数据与文献来源参数，刻画了符合筛查条件的智利女性的宫颈癌自然病程。直接医疗成本数据取自智利官方公开来源，并按1美元=938智利比索（CLP）的汇率换算为美元。研究开展了确定性敏感性分析与概率敏感性分析，同时还评估了30~64岁起始筛查的场景结果。两类基于高危型HPV DNA的初筛策略均优于标准护理方案（PAP-3）：既提升了健康收益，又实现了成本节约。在25~64岁的基础场景中，hrHPV–CINtec-5方案的健康增益最高，每女性可获得13003个增量质量调整生命年（Quality-Adjusted Life Year, QALYs），且每女性可节约16.65美元；而hrHPV–Pap-5方案则可节约32.57美元，对应12844个QALYs。概率敏感性分析证实了该方案的成本效益优势（绝大多数模拟结果位于成本-效果平面的东南象限），且在各类支付意愿范围内，其成本效益可接受度均超过90%。确定性敏感性分析显示，HPV16/18的感染进展风险与贴现率是影响研究结果的关键驱动因素。研究预测，在智利将宫颈癌筛查方案从PAP-3升级为基于高危型HPV DNA的初筛策略，可在改善健康结局的同时降低医疗成本。在所评估的基于高危型HPV DNA的初筛策略中，辅以hrHPV–CINtec-5分流的方案可获得最大健康增益，且仍能实现成本节约；而hrHPV–Pap-5方案则可实现最大程度的成本节省。上述研究结果可为智利国家宫颈癌筛查项目的现代化升级提供支持。