Background : Some studies in the literature suggest a possible role of multiple HPV infections as a prognostic factor in the development and progression of cervical neoplasia. we studied the cases of single and multiple HPV infection and analyzed the correlation with negative cases, and preneoplastic and neoplastic lesions of the uterine cervix with the aim of making a contribution to the prognostic factor under discussion Methods: 921 women with clinical HPV manifestations were enrolled. Inclusion criteria were: positive at the cytology for HPV lesions, presence of preneoplastic and neoplastic lesions of the uterine cervix diagnosed by the histology examination All the patients underwent colposcopy and cervical biopsy with viral genotyping. The search for viral DNA was carried out using polymerase chain reaction. Genotype 16 is correlated with the majority of CIN2+; we divided the multiple HPV16 infections into “infections with 16 as the first genotype” (16mHPV) (e.g. HPV 16 , 31, 52) and into “ infections containing 16” (m16HPV) (e.g. HPV 31, 16 , 52), we then divided them based on the number of genotypes present: infections with 2 strains, 3 strains, 4 strains, and > 4 strains. Results: We analyzed the differences between single and multiple infections with HPV16, the patients with single infections had a higher incidence of CIN2+ (83.3%) with respect to those with multiple infections (71.4%). The 16mHPV infection was significative for CIN2/CIN3. When the prevalence of the combinations between the genotypes was studied, we found that in 16mHPV infection HPV16, 18 and HPV 16, 31 were the most common combinations of mHPV infection (50%) and the most frequent in CIN2/CIN3 The 16mHPV infection with 2 genotypes, with respect to the infections with 3 or more genotypes, was significative with an OR= 7.94 (IC% 2.55-24.73). Conclusions: Our results suggest that single HPV infections give a higher risk of SCC development with respect to multiple HPV infections. Among multiple infections, only 16mHPV infection with 2 genotypes is associated with CIN2/CIN3 in a significative way and it presents an 8 times greater risk of developing a high grade lesion.