OBJECTIVES: Human Papilloma Virus (HPV) vaccination programs among women have been successfully implemented in Europe. Burden of HPV-related cancers is rising in Europe in men and represents around 30% of the overall HPV-related burden in both genders. Vaccinating girls have an indirect protective impact on males but doesn't avoid the whole HPV burden. Study objective was to have a first estimate of the incremental benefits of vaccinating males and females compared to females only, in Europe. METHODS: An Excel-based model was developed to estimate impact of vaccinating boys and girls with a quadrivalent-HPV6/11/16/18 vaccine on HPV-related diseases: anal, penile, head and neck, vaginal, vulvar and cervical cancers and genital warts. Epidemiological reductions due to vaccination were derived from a US dynamic transmission model. Epidemiological data and demographic inputs came from published literature. The analysis estimates the incremental clinical benefits of adding a cohort of 12-years old boys to a 12-years old girls vaccination program. Seventy percent vaccine coverage rates were assumed for both strategies.  RESULTS: A validation of this model was achieved by being able to replicate US dynamic model results (number of cases avoided). In Europe, female-only vaccination would result in a 61% reduction in males HPV-related cancers (at steady state; 100 years). Adding a cohort of boys would increase this result to 86% and would avoid significant additional HPV-related diseases (3,584 cancers, 88,514 genital warts annually). Head and neck cancers represent the majority of additional cancers avoided. Boys' vaccination would allow a further reduction in females' cases thanks to indirect protection. CONCLUSIONS: Model simulations were robust as they replicated US published results. This first analysis showed that vaccinating boys in addition of girls had the potential to prevent a significant number of additional cases. Country specific analysis will be useful to take into account different vaccination programs in place.