Estimated HPV-Attributable Inpatient Pharmaceutical Reimbursement in Bulgaria, 2021-2025: A National...

Background: Human papillomavirus (HPV)-attributable cancers remain largely preventable but continue to generate increasing treatment costs where vaccination and screening coverage are limited. We estimated direct inpatient pharmaceutical reimbursement attributable to HPV-related cancers in Bulgaria and examined the drivers of expenditure growth. Methods: National Health Insurance Fund reimbursement data (2021-2025) were analysed for antineoplastic medicines used to treat eight HPV-associated cancer sites. Site-specific population-attributable fractions (PAFs) were applied to estimate HPV-attributable expenditure. Uncertainty in PAFs was quantified using 10,000 Monte Carlo simulations and discrete attribution scenarios. Expenditure growth was decomposed into price, volume, and net product-entry/exit effects using Fisher indices. Expenditure was additionally expressed in constant 2021 euros using the Harmonised Index of Consumer Prices. Results: Estimated HPV-attributable inpatient pharmaceutical reimbursement totalled EUR 54.2 million (probabilistic median; 95% uncertainty interval: EUR 53.3-55.0 million). Cervical cancer accounted for 81.8% of the total. Results varied by less than ±6% across attribution scenarios and remained EUR 44.6 million when head-and-neck cancers were excluded. Annual expenditure increased from EUR 3.67 million in 2021 to EUR 19.89 million in 2025, representing a 5.4-fold nominal and 4.2-fold inflation-adjusted increase. Growth was concentrated in cervical cancer and was driven primarily by the introduction of new therapies rather than higher prices or greater use of existing medicines. Net product entry explained 88.8% of total log growth, while reimbursement prices for continuing products declined by approximately 31%. Pembrolizumab, first reimbursed for cervical cancer in 2023, accounted for EUR 16.03 million of cervical cancer expenditure in 2025. Conclusions: These ecological estimates indicate a rapid increase in HPV-attributable inpatient pharmaceutical reimbursement in Bulgaria, largely driven by cervical cancer and the introduction of immunotherapy. The findings have implications for budget forecasting, procurement planning, and economic evaluation of HPV prevention strategies.