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Human papillomaviruses (HPVs) are etiological agents of cervical cancer. In the absence of Pap smear alterations, high-risk HPV DNA can be detected in cervical samples. The prevalence of papillomavirus infection and their genotype distribution varies greatly across populations. The aims of this study were: i) to assess the prevalences of HPV genotypes in people living in Eastern Sicily (Italy) and the frequency of HPV multiple infections; ii) to evaluate the association between HPV genotypes and cervical lesions in order to improve the epidemiological knowledge useful for monitoring or treating infected women. Nested PCR and reverse dot/blot hybridization were used for the detection and typing of HPV DNA in 315 women who had had an abnormal PAP-smear. HPV DNA test was positive in 70.5% cases; the prevalence was 50% in atypical squamous cells of undetermined significance (ASCUS), 80.8% in low grade-, and 76.2% in high grade-squamous intraepithelial lesion (H-SIL). The genotype distribution showed a predominance of HPV-16 (56.7%) followed by HPV-18 (12.2%), HPV-31 (9.5%) and HPV-6 (9.5%). Multiple infections were detected in 35.1% of the infected patients. High frequency of positive results for HPV was confirmed and, even in case of ASCUS, patients should be taken into account for genotyping. Our data indicate that multiple infections are consistent in women with low-grade lesions while they are less frequent in women with H-SIL. This could reinforce the theory of the multi-stage cancer model, by which one HPV type becomes predominant along with the progression of cervical lesion severity.