OBJECTIVES: It is well known that a persistent infection by human papillomavirus (HPV) is an essential cause of cervical cancer. Prophylactic HPV vaccines aimed at preventing precancerous cervical lesions and cervical cancer are currently available and may be used for primary prevention of cervical cancer.  To define the efficiency of using HPV vaccine within a cervical cancer screening program with cytology compared with the strategy of only screening with cytology. METHODS: A comprehensive search of studies was developed in the main electronic databases including primary studies assessing HPV vaccine efficacy and/or safety or HPV. Meta-analysis was conducted when the studies were homogeneous. A decision analysis was performed using a Markov model based on the results of the systematic review and information about the natural history of the disease (HPV infection, cervical cancer). The model allowed to estimate cancer incidence and associated mortality, life expectancy and associated costs, with the objective of performing an economic evaluation. RESULTS: A total of 11 studies were included to assess HPV vaccines: 7 for efficacy and 11 for safety assessment. The efficacy of vaccine in preventing CIN2+ was 96% (95% CI: 91% to 98%). Modified intention-to-treat and intention-to-treat analyses were also undertaken and the results supported this trend although efficacy was lower. The economic evaluation showed that the vaccination strategy would imply a cost-effectiveness ratio of around €10,000 per quality life adjusted years (QALY). CONCLUSIONS: There is evidence from RCTs that the HPV vaccines are safe and effective in the prevention of cervical cancer precursor lesions. On top of this, this efficacy is reached with a reasonable cost-effectiveness ratio and within the accepable limits of the Spanish National Health System.