Physical Status and Variant Analysis of Human Papillomavirus 16 in Women from Shanghai

Abstract

Background/Aims: Human papillomavirus type 16 (HPV16) is the cause of more than half of all cases of cervical cancer. Genetic mutations in HPV16 and the integration of HPV16 DNA in the human genome are considered important genetic changes in cervical lesion progression. However, limited data concerning HPV16 lineages and physical integration status have been reported for Shanghai, China. The current study analyzed the genetic mutations in complete HPV16 genomes and the physical integration status of HPV16 DNA. Methods: A total of 30 samples of cervical exfoliated cells from patients with HPV16 infection were collected. The entire HPV16 genome was isolated, amplified by PCR and directly sequenced. The physical integration status was determined by 3′RACE nested PCR. Results: A total of 13 integration sites were identified, including 9 in common fragile sites and 1 not close to any fragile sites. Phylogenetic analysis identified two HPV lineages: the European (E) lineage and the East Asian (EA) lineage. Amino acid changes of D25E and N29S were the most common variations across the genome. The HPV16 early genes E1 and E7 and the late gene L1 tended to be highly conserved, whereas the early genes E2, E4 and E6 were more variable. Furthermore, 10 novel variations were identified in this study, which led to the 3 amino acid changes of S23I in E2 and E244K and T269I in E2/E4. Conclusion: Integrated HPV16 viruses were detected in all stages of cervical samples. Many variants in E2, E4, E7, and the long control region co-varied with E6 variations and helped to define the HPV16 lineages.

Genetic signatures for lineage/sublineage classification of HPV16, 18, 52 and 58 variants

“…It has been recommended to use the complete genomes to identify HPV variant lineages and sublineages [6]. However, ambiguous assignment may arise when the The sublineage distributions of the four HPV types in China generated in this study were consistent with previous reports [16,[33][34][35][36][37][38][39][40]. However, with the intensification of globalization, the genetic diversity of HPV in China and other parts of the planet remains dynamic and requires continuous surveillance.…”