Whole-genome analysis of human papillomavirus genotypes 52 and 58 isolated from Japanese women with cervical intraepithelial neoplasia and invasive cervical cancer

Abstract

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.

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.…”

“…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].…”

“…However, the cancer risk of HPV52 B variants was reported to be lower than lineage C [16]. Lineage A of HPV58 was found to be globally distributed and was the most prevalent in Asian females [16,33,35,37,38].…”

Detection of human papillomavirus type 52 in a case of gluteal squamous cell carcinoma

“…Although HPV 16/18 are the most common types implicated in cervical cancer worldwide, previous data show infection with HPV type 52 and 58 is more prevalent in cases of cervical cancer in Asian women. 5 With our finding in this patient, it should be assumed that HPV type 52 may be a risk for SCC in the Asian population.…”

Possible Risks of Human Tumor Virus Infection among Overseas Travelers in Japan

“…Thus, it is likely that the risk of infection with HPV in Japan is higher than that in developed countries with high HPV vaccination rate and that special attention is required for travelers visiting Japan. Also, it is important to note that other types of high-risk HPVs such as HPV52 and 58 are frequently detected in patients with cervical intraepithelial neoplasia and invasive cervical cancer in East Asian countries including Japan in addition to HPV 16 and 18 which are dominant in Europe and the United States [18].…”