Genetic diversity of human papillomavirus type 16 E6, E7, and L1 genes in Italian women with different grades of cervical lesions

High-risk human papillomaviruses (HPVs) are risk factors for the development of cervical cancer. HPV16 is themostcommontype, being present in about 60% of cervical cancers worldwide. Previous studies have reported upon the association between HPV 16 E6 variants and increased risk of cervical intraepithelial neoplasia and invasive cervical cancer. In this study, the presence of HPV 16polymorphisms in the E6, E7,andL1 geneswas investigated in relation to the presence of highgrade lesions. Sequencing of the E6 gene revealed the presence of nucleotide mutations resulting in15aminoacidchanges. Ofthese, theG134Dand C136R fall within the CXXC zinger finger domain important for p53 binding. In the E7 gene, four nucleotide variations were identified with two leading to the amino acid substitutions L15V and S31R. The L1 geneshowed13 nucleotide changes leading to 11 amino acid substitutions. Among these, the R364C and N367D are located at the baseof the HI-loop of theL1protein, considered to be the immunodominant epitope of HPV 16. No significant relationship between HPV 16 variants and high-grade lesions was found. Phylogenetic analysis showed that all the HPV 16 variants identified belonged to the European lineage, except one which was of the Asian-American lineage. The European-350G variant was detected most frequently (22 of 34, 64.7%). The study provides some new data on the genetic diversity of HPV 16 which may help to understand the oncogenic potential of the virus and to improve management of patients.