Vaccination can reduce the public health and economic burden of human papillomavirus (HPV)-associated diseases. In 2023, the Italian national immunization program (NIP) was updated to include HPV vaccination of females ≤26 and males ≤18 years. However, the cost-effectiveness of this update along with proposals to include additional cohorts is unknown. This study evaluates the cost-effectiveness of different HPV vaccination strategies in Italy over a 100-year period, using a published dynamic transmission model with Italy-specific input data. We modeled vaccination of the primary cohort (11 years of age) for 100 years, alone and supplemented with vaccination of additional cohorts for 5-100 years. We found that vaccination of the primary adolescent cohort resulted in substantial, sustained decreases in the incidence and mortality rates of all HPV-related cancers, but smaller, transient decreases in genital warts and recurrent respiratory papillomatosis. Adding supplementary vaccination of additional cohorts for 5-10 years had minor additional public health benefits, while continuing any of the modeled supplementary vaccination strategies for 100 years resulted in more substantial incremental benefits. For example, implementing the 2023-2025 NIP strategy for 100 years averted an additional 21,495 cases of cervical cancer compared to vaccination of the primary cohort alone. All supplementary vaccination strategies that were continued for 10 or 100 years were cost-effective compared to vaccination of the primary cohort alone at a willingness-to-pay threshold of €40,000 per quality-adjusted life year (QALY) gained. The benefits deriving from vaccinating additional cohorts should be considered when developing and updating NIPs.