Human Papillomavirus 42: A Novel Sublineage Identification, and Comparative Analysis of HPV42 Genetic Variability...

Although HPV 42 is classified as a low-risk HPV, it has been identified as an oncogenic driver of digital papillary adenocarcinoma (DPA) and is associated with high-grade squamous intraepithelial lesion (HSIL) in the mucosal genital region. This study aim to identify novel HPV42 sublineage, characterize its genetic variability, and explore the differences or associations of genetic variation between HPV42 variants derived from cervical and DPA samples. We successfully amplified 17 complete HPV42 genomes from cervical cells, including 5 A1, 11 A2, and 1 novel A4 sublineages. The A4 sublineage (SDWF08) was identified based on the phylogenetic analysis and pairwise distance of whole genome sequences, which differed by 0.57-0.70%, 0.50-0.74%, and 0.74% from A1, A2, and A3 sublineages, respectively. 13 A2 variants from China clustered into a minor branch, separate from other A2 sublineage. The A2 sublineage had the largest number of variation sites, with 71 single-nucleotide polymorphisms (SNPs) and 11 nonsynonymous amino acid mutations in E6, E7, E2, E4, L2, and L1. Three amino acids (P, S, I) deletions in E2 of SDWF08 overlaps with the deletion in E2 that originated from DPA. These HPV42 genomic sequences obtained in this study expand the number of publicly available, and provide an updated phylogenetic analysis to support further functional and evolutionary research on HPV42 genetic diversity. The observed deletions in E2 and the aspartate residue (D) upstream of the LxCxE motif in E7 may suggest a possible role for HPV42 in carcinogenesis, further functional studies are needed to validate this potential association.