OBJECTIVES: Human papillomavirus (HPV) has been implicated as a causal factor in cervical cancer (CC), the second most common cancer among women worldwide. Prophylactic vaccination against HPV-16/18 has been shown to be highly effective in preventing HPV related infections and pre-cancerous lesions. The aim of this study was to determine the potential clinical and economic impact of combining CC screening programme with HPV vaccination programme with the bivalent HPV-16/18 vaccine in women aged 25 (when CC screening starts) compared to screening alone. METHODS: A Markov cohort model was adapted to the Italian setting. The model replicates the HPV infection natural history leading to CC and includes the effect of screening and vaccination. Based on the latest results of the PATRICIA clinical trial for the bivalent vaccine, the vaccine efficacy includes cross-protection against non-vaccine HPV types 31/33/35/39/45/51/52/56/58/59. The vaccine efficacy in naïve girls and HPV-exposed women (>17-years old) was differentiated. Lifetime protection and 90% vaccination coverage were assumed. Costing was analysed from the perspective of the Italian health care system. Main outcomes are lifetime costs, QALYs, CC cases, deaths and ICER. Both costs and effects were discounted at 3% annually to calculate the ICER. RESULTS: The model shows that, compared to screening alone, vaccinating a single cohort of 330,000 women aged 25 would prevent over a lifetime 696 CC cases and 316 CC deaths (undiscounted) of which 131 and 59 respectively are due to cross-protection, with a discounted ICER of €33,918 per QALY gained. The ICER remains under the cost effective threshold defined by the WHO (between 1 and 3xGDP/capita). CONCLUSIONS: Under the assumptions of the model, extending vaccination to young adult women post-HPV exposure could lead to a substantial reduction in CC and remains cost effective in Italy compared with screening alone. Cross-protection would play an important role in this reduction.