Genetic characterization of variants of HPV‑16, HPV‑18 and HPV‑52 circulating in Italy among general and high‑risk populations

Viral factors, such as highrisk human papillomavirus variants, can increase the risk of viral persistence and influence the progression to cancer. In the present study, the long control region (LCR) of human papillomavirus (HPV)16 and HPV52, and the L1 region of HPV16 and HPV18, identified from subjects belonging to both general and highrisk populations (migrants, HIV+ subjects and adolescent/young people) residing in Italy, were characterized using molecular and phylogenetic techniques. To the best of our knowledge, this is the first Italian study to analyze a large number of sequences (n=458) and report phylogenetic data on the HPV52 variants. The phylogenetic analysis showed that 90% of the LCR variants of HPV16 and HPV52 clustered within lineage A (European lineage) and only sequences identified from subjects belonging to highrisk populations fell into the nonEuropean lineages. Analysis of the LCRs revealed a high genomic diversity with a large number of changes. Several mutations in the binding sites for viral and cellular transcription factors characterized the HPV16 LCR variants belonging to the African lineages B and C, were observed in subjects with cytological abnormalities (high squamous intraepithelial lesions). The HPV16 and HPV18 L1 molecular characterization identified 30% of changes in the immunedominant epitope loops. These data give a clear picture of the situation in Italy, and a starting point for understanding the molecular pathogenesis and developing molecular diagnostics for HPV, vaccines and other therapeutic approaches in order to control and/or eliminate virusinduced diseases.