The aim of the present study is to analyze the methodological and technical aspects of Health Technology Assessment (HTA) as a tool for the clinical and economic impact of vaccine interventions, describe and comment the main studies at the national level, with a particular focus on HPV vaccination. The work was conducted in 3 phases: a) revision of the scientific literature, strictly linked to methodologies adopted in different studies on economic evaluations on HPV vaccines and analysis of Guidelines for building models for the economic assessment; b) analysis of the peculiarities and critical elements of economic evaluations in the field of vaccinology, from the clinical and epidemiological point of view, as well as the recognition of lack of knowledge on HPV infection dynamics; c) a comparative analysis of the two italian studies and of the results coming from them. Many differences between studies were found. Nevertheless, there is a general agreement on the economic profile of HPV vaccination for adolescent girls, if compared with the actual practice on the prevention of cervical carcinoma (pap-test screening). All the models showed a significant impact in terms of reduction of the incidence of cervical carcinoma and related mortality, in the long run, as well as a reduction of pre-cancer lesions and abnormal Pap tests. HTA approach has been recently recognized as a tool for decision making in vaccinology, and its methodologies and procedures are currently debated by public health experts. There is a strong need to continue the work in improving the model techniques of economic evaluations concerning HPV vaccination, as well as the adoption of homogeneous methods and standards, with the aim of helping the decision process in the field of Public Health.