Association of cervical carcinogenesis risk with HPV16 E6 and E7 variants in the Taizhou area, China

Dai, Meizhen; Qiu, Yi; Di, Xing-Hong; Shi, Wei-Wu; Xu, Huihui

doi:10.1186/s12885-021-08531-y

Cited by 7 publications

(6 citation statements)

References 42 publications

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“…According to our previous findings, the odds ratio (OR) for CIN2 + in women infected with α-9 HPV is 3.2 when compared to women infected with α-5, α-6, or α-7 [ 7 ]. The genetic variation of E6 or E7 genes may correlate highly with cancer risk in Taizhou [ 21 – 23 ]. Therefore, E6 or E7 molecules might be regarded as ideal targets for HPV therapeutic vaccine development and cervical cancer treatment.…”

Section: Discussionmentioning

confidence: 99%

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Yuan,

Yan,

Gan

et al. 2024

BMC Genomics

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Background Alpha-papillomavirus 9 (α-9) is a member of the human papillomavirus (HPV) α genus, causing 75% invasive cervical cancers worldwide. The purpose of this study was to provide data for effective treatment of HPV-induced cervical lesions in Taizhou by analysing the genetic variation and antigenic epitopes of α-9 HPV E6 and E7. Methods Cervical exfoliated cells were collected for HPV genotyping. Positive samples of the α-9 HPV single type were selected for E6 and E7 gene sequencing. The obtained nucleotide sequences were translated into amino acid sequences (protein primary structure) using MEGA X, and positive selection sites of the amino acid sequences were evaluated using PAML. The secondary and tertiary structures of the E6 and E7 proteins were predicted using PSIPred, SWISS-MODEL, and PyMol. Potential T/B-cell epitopes were predicted by Industrial Engineering Database (IEDB). Results From 2012 to 2023, α-9 HPV accounted for 75.0% (7815/10423) of high-risk HPV-positive samples in Taizhou, both alone and in combination with other types. Among these, single-type-positive samples of α-9 HPV were selected, and the entire E6 and E7 genes were sequenced, including 298 HPV16, 149 HPV31, 185 HPV33, 123 HPV35, 325 HPV52, and 199 HPV58 samples. Compared with reference sequences, 34, 12, 10, 2, 17, and 17 nonsynonymous nucleotide mutations were detected in HPV16, 31, 33, 35, 52, and 58, respectively. Among all nonsynonymous nucleotide mutations, 19 positive selection sites were selected, which may have evolutionary significance in rendering α-9 HPV adaptive to its environment. Immunoinformatics predicted 57 potential linear and 59 conformational B-cell epitopes, many of which are also predicted as CTL epitopes. Conclusion The present study provides almost comprehensive data on the genetic variations, phylogenetics, positive selection sites, and antigenic epitopes of α-9 HPV E6 and E7 in Taizhou, China, which will be helpful for local HPV therapeutic vaccine development.

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Section: Discussionmentioning

confidence: 99%

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Yuan,

Yan,

Gan

et al. 2024

BMC Genomics

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“…16HB01, which simultaneously had the variants T178G (D32E), A647G (N29S) and T846C, was the most prevalent (58/168, 34.5%) in the 45 variant groups. In Taizhou, China, T178G (D32E) in E6 and A647G (N29S) and T846C in E7 occur in 96.4% of the A4 (Asian) variants [ 34 ]. In this study, twelve nonsynonymous variants in the sequences encoding E6 or E7 proteins were found, which may affect the folding of oncoproteins in the secondary structure and result in differences in their ability to interact with tumor suppressor proteins and the pathogenicity of HPV-16.…”

Section: Discussionmentioning

confidence: 99%

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China

Li,

Yang,

Zhang

et al. 2023

Virol J

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Background Persistent high-risk human papillomavirus (HR-HPV) infection is an important factor in the development of cervical cancer, and human papillomavirus type 16 (HPV-16) is the most common HR-HPV type worldwide. The oncogenic potential of HPV-16 is closely related to viral sequence variation. Methods In order to clarify the variant characteristics of HPV-16 E6 and E7 genes in central China, E6 and E7 sequences of 205 HPV‐16 positive samples were amplified by polymerase chain reaction. PCR products of E6 and E7 genes were further sequenced and subjected to variation analysis, phylogenetic analysis, selective pressure analysis and B-cell epitope prediction. Results Twenty-six single nucleotide variants were observed in E6 sequence, including 21 non-synonymous and 5 synonymous variants. Twelve single nucleotide variants were identified in E7 sequence, including 6 non-synonymous and 6 synonymous variants. Four new variants were found. Furthermore, nucleotide variation A647G (N29S) in E7 was significantly related to the higher risk of HSIL and cervical cancer. Phylogenetic analysis showed that the E6 and E7 sequences were all distributed in A lineage. No positively selected site was found in HPV-16 E6 and E7 sequences. Non-conservative substitutions in E6, H31Y, D32N, D32E, I34M, L35V, E36Q, L45P, N65S and K75T, affected multiple B-cell epitopes. However, the variation of E7 gene had little impact on the corresponding B-cell epitopes (score < 0.85). Conclusion HPV-16 E6 and E7 sequences variation data may contribute to HR-HPV prevention and vaccine development in Jingzhou, central China.

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“…Pakistan is one of the populous countries contributing to the worldwide burden of CC, out of which HPV16 is commonly found in women with cervical and oral cancer worldwide in numerous studies and few HPV16 variants are highly oncogenic in contrast to others. [25][26][27] This is the first national study that used WGS of HPV16, the most frequent HR-HPV type recognized in community-based studies carried out in Pakistan from 2016 to 2021. 3,5,18 The study presented here was not designed to evaluate persistence but rather aims to reveal HPV16 genetic polymorphism and some unique HPV16 variants circulating in Pakistani women.…”

Section: Discussionmentioning

confidence: 99%

Whole-genome analysis and evolutionary characterization of cervical and oral human papillomavirus 16

Minhas,

Kashif,

Nisar

et al. 2023

Exp Biol Med (Maywood)

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High-throughput genome-wide sequencing has revealed high genomic variability of HPV16 in different geographic regions which is the most predominant genotype in human papillomavirus (HPV)–associated malignancies. Analysis of the HPV16 by whole-genome sequence (WGS) is an advanced method for the identification of mutations in the genome. There is limited information about HPV16 diversity in Pakistan, especially at the genomic level. Till now, WGS for HPV16 has not been previously reported in Pakistan. The current study has sequenced three HPV16 viral genomes, from two cervical and one oral cavity positive sample of women presented with general gynecological problems without any evidence of precancerous or cancerous lesions using an ion ampliseq customized panel. Sequencing analysis detected 38 variations, including single-nucleotide polymorphisms (SNPs) and two Indels, across three samples with the highest number of SNPs present in E1, E2, and L2, respectively. A total of 20 non-synonymous and 11 synonymous mutations with amino acid substitutions (T1421C, G1515A, T2223C, T1389C, G1483A, and T2191C) were identified. The phylogenetic analysis revealed the genomes of HPV16 are closely associated with those reported from Thailand and the United States. These are the first HPV16 WGS from Pakistan. However, more research is needed with a large sample size from diversified areas to assess the carcinogenic consequences and impact of HPV vaccinations.

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Association of cervical carcinogenesis risk with HPV16 E6 and E7 variants in the Taizhou area, China

Cited by 7 publications

References 42 publications

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Phylogenetic analysis and antigenic epitope prediction for E6 and E7 of Alpha-papillomavirus 9 in Taizhou, China

Genetic variation of E6 and E7 genes of human papillomavirus type 16 from central China

Whole-genome analysis and evolutionary characterization of cervical and oral human papillomavirus 16

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