Unique LCR variations among lineages of HPV16, 18 and 45 isolates from women with normal cervical cytology in Ghana

Abstract

BackgroundIn addition to being useful for classification, sequence variations of human Papillomavirus (HPV) genotypes have been implicated in differential oncogenic potential and a differential association with the different histological forms of invasive cervical cancer. These associations have also been indicated for HPV genotype lineages and sub-lineages. In order to better understand the potential implications of lineage variation in the occurrence of cervical cancers in Ghana, we studied the lineages of the three most prevalent HPV genotypes among women with normal cytology as baseline to further studies.MethodsOf previously collected self- and health personnel-collected cervical specimen, 54, which were positive for HPV16, 18 and 45, were selected and the long control region (LCR) of each HPV genotype was separately amplified by a nested PCR. DNA sequences of 41 isolates obtained with the forward and reverse primers by Sanger sequencing were analysed.ResultsNucleotide sequence variations of the HPV16 genotypes were observed at 30 positions within the LCR (7460 – 7840). Of these, 19 were the known variations for the lineages B and C (African lineages), while the other 11 positions had variations unique to the HPV16 isolates of this study. For the HPV18 isolates, the variations were at 35 positions, 22 of which were known variations of Africa lineages and the other 13 were unique variations observed for the isolates obtained in this study (at positions 7799 and 7813). HPV45 isolates had variations at 35 positions and 2 (positions 7114 and 97) were unique to the isolates of this study.ConclusionThis study provides the first data on the lineages of HPV 16, 18 and 45 isolates from Ghana. Although the study did not obtain full genome sequence data for a comprehensive comparison with known lineages, these genotypes were predominately of the Africa lineages and had some unique sequence variations at positions that suggest potential oncogenic implications. These data will be useful for comparison with lineages of these genotypes from women with cervical lesion and all the forms of invasive cervical cancers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-017-0755-z) contains supplementary material, which is available to authorized users.

Genetic variability and functional implication of HPV16 from cervical intraepithelial neoplasia in Shanghai women

“…The LCR displayed greater sequence variability than any other region in the HPV16 genome, which was consistent with our results showing that the nucleotide variation rate of LCR was 8.17%. This region includes several binding sites for cellular and viral TFs, which regulate the replication of HPV16 and the transcriptional activity of the early regions . In the present study, 25 loci identified in the LCR of the various sequences are embedded in the putative binding sites for transcription factors TBP, Ftz, USF, Hb, Oct‐1, C/EBP α, GR_α, YY1, AP‐1, NF‐1, Pit‐1α, E2, and ICSBP.…”

“…The high‐quality database for transcription factor binding profile, JASPAR was used to investigate the possible cellular and viral transcription factors binding sites within the HPV16 LCR . The threshold for the relative profile score was set at 80%.…”

“…Dong Hang also found that the appearance of A4 variants among HPV16 positive women conferred a remarkably lifted chance of gaining cervical cancer . Furthermore, some studies revealed phylogenetic relationships on the basis of the sequences of HPV16 E6 , E7 , and the long control region ( LCR ) in cervical cast‐off cells from Uruguayan and Ghanaian women . These relationships may offer new insights for the genetic divergence in the carcinogenicity caused by HPV16 variants.…”

Epidemiology and Burden of Human Papillomavirus and Related Diseases, Molecular Pathogenesis, and Vaccine Evaluation

“…These main groups or lineages perfectly correspond to the existing main human races: Africans (Af-1 and Af-2), Caucasians (E), and Asians (As and AA) ( 96 ). This statement, based solely on studies of HPV 16 isolates, could be generalized to all papillomaviruses ( 80 , 96 – 100 ), as a similar description was established for the inter-population variability found in HPV 18, 33, and 45 ( 76 , 77 , 101 , 102 ). This inter-population variability made it possible to explain that HPVs from the same type induce different gene expression profiles associated with a certain disease occurrence risk, and thus to understand why in some regions the burden of HPV-associated diseases is higher than in others, for the same variants, as presented previously ( 100 ).…”

Designing of CD8⁺ and CD8⁺-overlapped CD4⁺ epitope vaccine by targeting late and early proteins of human papillomavirus

“…2,16,33 Based on the level of enrichment in cervical cancer cases compared to women with normal cytological features, HPV45 has been suggested as the third highest oncogenic agent next to HPV16 and 18. 1,30,34,35 In comparison to other hrHPV types, limited reports exist about the peptide research in HPV45.…”