OBJECTIVES: A new human papillomavirus (HPV) vaccine protects against the 9 HPV types responsible for 90% of HPV-related cancers (cervix, anus, vulva, vagina). It includes the 4 types contained in the quadrivalent (HPV 6,11,16,18) and 5 additional high-risk HPV types (HPV 31, 33, 45, 52, 58). The analysis aimed at estimating the incremental public health impact and cost-effectiveness of 2 different interventions in Italy: 1) girl vaccination with a ninevalent HPV vaccine compared to a quadrivalent vaccine; 2) universal (girls and boys) vaccination programme with a ninevalent HPV vaccine compared to a quadrivalent vaccine. METHODS: A dynamic transmission model including a wide range of health and cost outcomes related to cervical, anal, vulvar, vaginal diseases and genital warts was calibrated to Italian epidemiological data. The clinical impact due to the 5 new types was included for cervical diseases only, producing conservative outcomes. In the base case, a two-dose schedule, lifelong vaccine type-specific protection and a vaccination coverage rate of 71% for the 12-year old cohorts were assumed. A threshold of 30,000€/QALY-gained was considered. Different prices assumptions were used for the ninevalent vaccine (from 0% to 40% higher than that of the quadrivalent HPV vaccine). Deterministic sensitivity analyses on key parameters (such as duration of protection, discount rate) were conducted. RESULTS: Over 100 years, between 21,000 to 22,000 cervical cancers and between 272,600 and 288,790 pre-cancerous cervical lesions could be avoided with the implementation of a ninevalent vaccine. The cost-effectiveness ratio of the ninevalent vaccine is estimated to remain well below the threshold with all the different price assumptions considered. CONCLUSIONS: Both scenarios with a ninevalent vaccine in Italy are estimated to be from cost saving to highly cost-effective across a range of sensitivity analyses and are expected to further reduce the public health burden of HPV-related cancers and diseases.