BUDGET IMPACT ANALYSIS OF THE IMPLEMENTATION OF AN ORGANIZED CERVICAL CANCER SCREENING PROGRAM BASED ON PRIMARY HPV AND CYTOLOGY STRATIFIED BY VACCINATION STATUS IN THE METROPOLITAN AREA OF MILAN.

Background. Cervical cancer is largely preventable through vaccination and screening; however, disparities in access and inefficient resource use persist. Prior to 2022, cervical cancer screening in the Metropolitan Area of Milan was conducted solely in opportunistic setting, likely resulting in high rates of inappropriate testing and unequal participation. In 2022, an organized screening program based on primary HPV testing with cytology triage, stratified by vaccination status, was launched. This study aimed to assess the year-to-year impact of the program implementation on screening budget, both organized and opportunistic from 2024 to 2033. Methods. A Budget Impact Model (BIM) was developed to simulate annual volumes of screening test, colposcopies, and associated expenditures over the period 2024-2033, according to a predefined implementation plan. Model inputs were derived from screening registries and administrative health databases covering 2018-2019 (pre-implementation) and 2022-2023 (post-implementation). Parameters included age, round, vaccination status and test-specific participation rates, HPV positivity rates, colposcopy referral rates, and average follow-up colposcopies. One-way sensitivity analyses were conducted to identify parameters most affecting total costs and service demand. The AdViSHE checklist was provided to describe the validation efforts for the conceptual and the computing framework, and calibration was performed using real-world data from 2024 cervical cancer screening program in the Metropolitan Area of Milan. Results. The implementation of organized screening substantially increased publicly funded screening coverage (from 12.5% to 40%), shifting the text mix from cytology to primary HPV DNA testing. The program is projected to generate a temporary surge in colposcopy demand (2025-2027), reflecting the detection of prevalent lesions in previously unscreened women. Annual screening costs are expected to rise initially – peaking in 2025 (€2.65 million) and 2030 (€2.61 million) – before stabilizing at sustainable levels. Five alternative scenarios were simulated to explore more sustainable policy options. Among them, the co-test scenario - in which the program performs co-tests prior to follow up colposcopies – proved to be the less costly option, while allowing for potential future increases in participation.Sensitivity analyses identified HPV participation rate, HPV positivity with normal cytology, and HPV referral rates as the main drivers of both organized screening costs and colposcopy volumes. Conclusions. The transition from opportunistic to organized HPV-based screening in Milan produced significant benefits in terms of coverage, efficiency and equity, despite short-term increases in diagnostic workload and moderate long-term cost growth. Policymakers should carefully plan transitional phases, ensuring adequate colposcopy and laboratory capacity. Continued investments in organized screening, integration with vaccination and follow-up programs, and regulation of opportunistic testing are essential to maximize the long-term public health benefits and economic sustainability of HPV-based cervical cancer screening.