Abstract:IntroductionHuman papillomavirus (HPV) 52 is a carcinogenic, high-risk genotype frequently detected in cervical cancer cases from East Asia, including Korea.Materials and MethodsSequences of HPV52 detected in 91 cervical samples collected from women attending Seoul St. Mary’s Hospital were analyzed. HPV52 genomic sequences were obtained by polymerase chain reaction (PCR)-based sequencing and analyzed using Seq-Scape software, and phylogenetic trees were constructed using MEGA6 software.ResultsOf the 91 cervica… Show more
“…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.…”
Section: Discussionsupporting
confidence: 76%
“…Rest of HPV52 sequences belonged to A1 (n=2), C2 (n=3) and D (n=1), and HPV58 to B2 (n=1). HPV52 lineages B and C were common in Asian countries, with B the most prevalent in China [34][35][36]. However, the cancer risk of HPV52 B variants was reported to be lower than lineage C [16].…”
Section: Genetic Diversity Of Verification Datasetmentioning
Increasing evidences indicate that high-risk HPV variants are heterogeneous in carcinogenicity and ethnic dispersion. In this work, we identified genetic signatures for convenient determination of lineage/sublineage of HPV16, 18, 52 and 58 variants. Using publicly available genomes, we found that E2 of HPV16, L2 of HPV18, L1 and LCR of HPV52, and L2, LCR and E1 of HPV58 contain the proper genetic signature for lineage/sublineage classification. Sets of hierarchical signature nucleotide positions (SNPs) were further confirmed for high accuracy (>98%) by classifying HPV genomes obtained from Chinese females, which included 117 HPV16 variants, 48 HPV18 variants 117 HPV52 variants and 89 HPV58 variants. The circulation of HPV variants posing higher cancer risk in Eastern China, such as HPV16 A4 and HPV58 A3, calls for continuous surveillance in this region. The marker genes and signature nucleotide positions may facilitate cost-effective diagnostic detections of HPV variants in clinical settings.
“…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.…”
Section: Discussionsupporting
confidence: 76%
“…Rest of HPV52 sequences belonged to A1 (n=2), C2 (n=3) and D (n=1), and HPV58 to B2 (n=1). HPV52 lineages B and C were common in Asian countries, with B the most prevalent in China [34][35][36]. However, the cancer risk of HPV52 B variants was reported to be lower than lineage C [16].…”
Section: Genetic Diversity Of Verification Datasetmentioning
Increasing evidences indicate that high-risk HPV variants are heterogeneous in carcinogenicity and ethnic dispersion. In this work, we identified genetic signatures for convenient determination of lineage/sublineage of HPV16, 18, 52 and 58 variants. Using publicly available genomes, we found that E2 of HPV16, L2 of HPV18, L1 and LCR of HPV52, and L2, LCR and E1 of HPV58 contain the proper genetic signature for lineage/sublineage classification. Sets of hierarchical signature nucleotide positions (SNPs) were further confirmed for high accuracy (>98%) by classifying HPV genomes obtained from Chinese females, which included 117 HPV16 variants, 48 HPV18 variants 117 HPV52 variants and 89 HPV58 variants. The circulation of HPV variants posing higher cancer risk in Eastern China, such as HPV16 A4 and HPV58 A3, calls for continuous surveillance in this region. The marker genes and signature nucleotide positions may facilitate cost-effective diagnostic detections of HPV variants in clinical settings.
“…For HPV18, mutations related to carcinogenicity were rarely reported. For HPV52, Choi et al reported that A379G (E6 K93R) might be linked with higher disease severity and that this mutation was mainly occurred in sublineage B2 [31]. In our study, we showed that A379G mutation occurred in not only sublineage B2, but also in A2 and B1 (Supplementary Table S5).…”
Persistent infections of high-risk human papillomaviruses (HPVs) are the leading cause of cervical cancers. We collected cervical exfoliated cell samples from females in Changsha city, Hunan Province and obtained 358 viral genomes of four major HPV types, including HPV 16 (n=82), 18 (n=35), 52 (n=121) and 58 (n=100). The lineage/sublineage distribution of the four HPVs confirmed previous epidemiological reports, with the predominant prevailing sublineage as A4 (50%), A1 (37%) and A3 (13%) for HPV16, A1 (83%) for HPV18, B2 (86%) for HPV52 and A1 (65%), A3 (19%) and A2 (12%) for HPV58. We also identified two potentially novel HPV18 sublineages, i.e. A6 and A7. Virus mutation analysis further revealed the presence of HPV16 and HPV58 strains associated with potentially high oncogenicity. These findings expanded our knowledge on the HPV genetic diversity in China, providing valuable evidence to facilitate HPV DNA screening, vaccine effectiveness evaluation and control strategy development.
“…These findings are in good agreement with a general trend in HPV52/58 variant distributions, suggesting that HPV52 lineage B and HPV58 lineage A are more prevalent in Asia than in Europe, the Americas, and Africa [ 16 , 32 ]. Further, a high prevalence of lineage B in HPV52-positive cervical specimens was reported in South Korea [ 33 ] and Taiwan [ 17 ], and the dominance of lineage A in HPV58-positive specimens was also observed in Taiwan [ 17 ], which strongly suggests that such biased distributions of HPV52/58 variant lineages are common among East Asian countries.…”
BackgroundHuman papillomavirus genotypes 52 and 58 (HPV52/58) are frequently detected in patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC) in East Asian countries including Japan. As with other HPV genotypes, HPV52/58 consist of multiple lineages of genetic variants harboring less than 10% differences between complete genome sequences of the same HPV genotype. However, site variations of nucleotide and amino acid sequences across the viral whole-genome have not been fully examined for HPV52/58. The aim of this study was to investigate genetic variations of HPV52/58 prevalent among Japanese women by analyzing the viral whole-genome sequences.MethodsThe entire genomic region of HPV52/58 was amplified by long-range PCR with total cellular DNA extracted from cervical exfoliated cells isolated from Japanese patients with CIN or ICC. The amplified DNA was subjected to next generation sequencing to determine the complete viral genome sequences. Phylogenetic analyses were performed with the whole-genome sequences to assign variant lineages/sublineages to the HPV52/58 isolates. The variability in amino acid sequences of viral proteins was assessed by calculating the Shannon entropy scores at individual amino acid positions of HPV proteins.ResultsAmong 52 isolates of HPV52 (CIN1, n = 20; CIN2/3, n = 21; ICC, n = 11), 50 isolates belonged to lineage B (sublineage B2) and two isolates belonged to lineage A (sublineage A1). Among 48 isolates of HPV58 (CIN1, n = 21; CIN2/3, n = 19; ICC, n = 8), 47 isolates belonged to lineage A (sublineages A1/A2/A3) and one isolate belonged to lineage C. Single nucleotide polymorphisms specific for individual variant lineages were determined throughout the viral genome based on multiple sequence alignments of the Japanese HPV52/58 isolates and reference HPV52/58 genomes. Entropy analyses revealed that the E1 protein was relatively variable among the HPV52 isolates, whereas the E7, E4, and L2 proteins showed some variations among the HPV58 isolates.ConclusionsAmong the HPV52/58-positive specimens from Japanese women with CIN/ICC, the variant distributions were strongly biased toward lineage B for HPV52 and lineage A for HPV58 across histological categories. Different patterns of amino acid variations were observed in HPV52 and HPV58 across the viral whole-genome.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-017-0155-4) contains supplementary material, which is available to authorized users.
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