OBJECTIVES: The current study has been designed to investigate risk factors influencing the viral transmission and development of HPV infections within the Italian population. METHODS: A standardized and computer-guided questionnaire was administered to male and female patients with a HPV-induced pathology (e.g. atypical squamous cells of undetermined significance, cervical intraepithelial neoplasia, cervical cancer, anal-colorectal cancer, head-neck cancer and anogenital warts). Six clinical centres across Italy participated in this multicentre study. The patients’ risk profile was assessed and compared to that of a control group of healthy subjects attending the same clinics. The effects of risk factors were evaluated using a backwards stepwise multivariate logistic regression model with covariate adjustment. The following predictors were included: level of education, occupation, age at first intercourse, number of sexual partners, smoking, previous sexually transmitted  diseases, age at first pap smear, pap smear frequency, use of oral contraceptives and the number of pregnancies. RESULTS: Overall, 600 respondents were eligible for the analysis, consisting of 465 patients (44.0±16.3 years) and 135 controls (44.0±13.2 years). More than 5 sexual partners increased the risk of acquiring HPV infections up to 2.52-fold (95%CI: 1.34-4.74), while smoking or an early sexual debut (≤ 18 years) raised it by about a factor of 1.62. Higher levels of education were associated with a protective effect. The overall rate of individuals at high risk with more than 5 sexual partners and at least another additional factor corresponded to 26.3% (158 out of 600). The proportion of subjects with an average risk (respondents with less than 5 partners and at least another additional factor) amounted to 53.2% (319 out of 600). CONCLUSIONS: Analysis of risk factors can be used as part of the economic assessment of other effective HPV vaccination strategies, including an immunization programme for pre-adolescents of both sexes in Italy.