OBJECTIVES: Compare the epidemiological and economic impact of accrued cross-protection against oncogenic human papillomavirus (HPV) types beyond 16/18 provided by the bivalent vaccine (bi-v) vs. additional protection against non-oncogenic HPV types 6/11 of the quadrivalent vaccine (quadri-v), in France METHODS: A lifetime Markov model calibrated to the French setting was developed to reflect the natural history of low- (evolving to genital warts - GWs) and high-risk HPV (evolving to cervical cancer - CC) infections, together with screening and vaccination effects, for a single age cohort of 370,000 14-year-old girls (70% coverage). Transition probabilities, costs and utility were estimated from literature, official tariffs and expert opinions. Vaccine efficacy was obtained from recent phase III clinical trials (HPV-008 for bi-v and FUTURE I-II for quadri-v), for comparable cohorts on pre-sexual debut population (infection naïve). Life-long protection was assumed for both vaccines. Number of Cervical Intraepithelial Neoplastic lesions (CIN), CC, CC deaths and GW, QALY and costs were estimated. Costs and outcomes (discounted at 3% and 1.5% respectively) were compared from a societal perspective without indirect costs. RESULTS: Cross-protection of bi-v vs. quadri-v led to additional 29,587 CIN1, 2,928 CIN2+, 99 CC and 32 deaths prevented, while quadri-v prevented 14,302 GWs. It resulted in additional 556 QALY gained for bi-v The remaining CIN, CC and GW not prevented by vaccines would cost M€39 for  and M€37 for  At the current public prices of €111.82 for bi-v and €123,66 for quadri-v per dose, the vaccination program would cost M€143 and M€150 and be cost-effective at an estimated ICER/QALY of €10,611 and €11,833 respectively vs. the absence of vaccination. CONCLUSIONS: Both vaccines have different epidemiological impacts with an increased number of cancer cases prevented for bi-v, though in France, the economic impact of HPV mass vaccination is similar whatever the vaccine selected