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 high‑risk 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 HPV‑52, and the L1 region of HPV‑16 and HPV‑18, identified from subjects belonging to both general and high‑risk 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 HPV‑52 variants. The phylogenetic analysis showed that 90% of the LCR variants of HPV‑16 and HPV‑52 clustered within lineage A (European lineage) and only sequences identified from subjects belonging to high‑risk populations fell into the non‑European 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 HPV‑16 LCR variants belonging to the African lineages B and C, were observed in subjects with cytological abnormalities (high squamous intraepithelial lesions). The HPV‑16 and HPV‑18 L1 molecular characterization identified 30% of changes in the immune‑dominant 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 virus‑induced diseases.