Skip to main content
Top
Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Human Papillomavirus | Primary research

Genetic variations in E6, E7 and the long control region of human papillomavirus type 16 among patients with cervical lesions in Xinjiang, China

Authors: Xiangyi Zhe, Huizhen Xin, Zhenzhen Pan, Fuyuan Jin, Weinan Zheng, Hongtao Li, Dongmei Li, Dongdong Cao, Ying Li, Chunhe Zhang, Shaowei Fu, Renfu Shao, Zemin Pan

Published in: Cancer Cell International | Issue 1/2019

Login to get access

Abstract

Background

Xinjiang is one of the areas with the highest incidence of cervical cancer in China. Genetic variation in Human papillomavirus type 16 (HPV16) may increase the ability of the virus to mediate carcinogenesis and immune escape, which are risk factors for the progression of cervical cancer. We investigated polymorphism in HPV16 and the distribution of its sub-lineages in the region by analyzing the E6, E7 and long control region (LCR) gene sequences from women with HPV16-positive cervical samples in Xinjiang.

Methods

A total of 138 cases of cervical lesions and squamous cell carcinoma with infection of HPV16 virus were collected. The E6 and E7 genes and LCR of HPV16 virus were sequenced and compared with the HPV16 European prototype reference and other HPV16 mutants for single nucleotide polymorphisms. Neighbor-joining phylogenetic trees were constructed using E6, E7 and LCR sequences.

Results

Fourteen missense mutations were found in the E6 gene; the loci with the highest mutation frequency were T350G (36/75, 48%) and T178G (19/75, 25.3%). In the E7 gene, the locus with the highest mutation frequency was A647G (18/75, 24%). A total of 33 polymorphic sites were found in the LCR, of which T7447C (39/95, 40.1%) was the most frequent.

Conclusion

HPV16 in Xinjiang is mainly of the European variant, followed by the Asian variant type; no Africa 1, 2 or Asia–America variant types were found.
Literature
1.
go back to reference Wu LX, Yun LI, Mu LI, Li FX, Cui MY, Yang Y, et al. The expression and clinical significance of Sox 11 in cervical carcinogenesis. J Xi’an Jiaotong Univ (Medical Sciences). 2018;39(1):73–7. Wu LX, Yun LI, Mu LI, Li FX, Cui MY, Yang Y, et al. The expression and clinical significance of Sox 11 in cervical carcinogenesis. J Xi’an Jiaotong Univ (Medical Sciences). 2018;39(1):73–7.
2.
go back to reference Iancu IV, Anton G, Botezatu A, Huica I, Nastase A, Socolov DG, et al. LINC01101 and LINC00277 expression levels as novel factors in HPV-induced cervical neoplasia. J Cell Mol Med. 2017;21(12):3787–94.CrossRef Iancu IV, Anton G, Botezatu A, Huica I, Nastase A, Socolov DG, et al. LINC01101 and LINC00277 expression levels as novel factors in HPV-induced cervical neoplasia. J Cell Mol Med. 2017;21(12):3787–94.CrossRef
3.
go back to reference Song D, Shi Q, Hou X, Zhenghai MA. The effect of mutations in the upstream regulatory region of HPV-16 on the activity of virus early promoter. China Oncol. 2017;27(2):109–14. Song D, Shi Q, Hou X, Zhenghai MA. The effect of mutations in the upstream regulatory region of HPV-16 on the activity of virus early promoter. China Oncol. 2017;27(2):109–14.
4.
go back to reference Jackson R, Rosa BA, Lameiras S, Cuninghame S, Bernard J, Floriano WB, et al. Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology. BMC Genom. 2016;17:851.CrossRef Jackson R, Rosa BA, Lameiras S, Cuninghame S, Bernard J, Floriano WB, et al. Functional variants of human papillomavirus type 16 demonstrate host genome integration and transcriptional alterations corresponding to their unique cancer epidemiology. BMC Genom. 2016;17:851.CrossRef
5.
go back to reference Zhao JW, Fang F, Guo Y, et al. HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability. J Exp Clin Cancer Res. 2016;35(1):180.CrossRef Zhao JW, Fang F, Guo Y, et al. HPV16 integration probably contributes to cervical oncogenesis through interrupting tumor suppressor genes and inducing chromosome instability. J Exp Clin Cancer Res. 2016;35(1):180.CrossRef
6.
go back to reference Tzenov YR, Andrews PG, Voisey K, Popadiuk P, Xiong J, Popadiuk C, et al. Human papilloma virus (HPV) E7-mediated attenuation of retinoblastoma (Rb) induces hPygopus2 expression via Elf-1 in cervical cancer. Mol Cancer Res. 2013;11(1):19–30.CrossRef Tzenov YR, Andrews PG, Voisey K, Popadiuk P, Xiong J, Popadiuk C, et al. Human papilloma virus (HPV) E7-mediated attenuation of retinoblastoma (Rb) induces hPygopus2 expression via Elf-1 in cervical cancer. Mol Cancer Res. 2013;11(1):19–30.CrossRef
7.
go back to reference Lopera EA, Baena A, Florez V, Montiel J, Duque C, Ramirez T, et al. Unexpected inverse correlation between Native American ancestry and Asian American variants of HPVl6 in admixed colombian cervical cancer cases. Infect Genet Evol. 2014;28:339–48.CrossRef Lopera EA, Baena A, Florez V, Montiel J, Duque C, Ramirez T, et al. Unexpected inverse correlation between Native American ancestry and Asian American variants of HPVl6 in admixed colombian cervical cancer cases. Infect Genet Evol. 2014;28:339–48.CrossRef
8.
go back to reference Mosmann JP, Monetti MS, Frutos MC, Kiguen AX, Venezuela RF, Cuffini CG. Mutation detection of E6 and LCR genes from HPV 16 associated with carcinogenesis. Asian Pac J Cancer Prev. 2015;16(3):1151–7.CrossRef Mosmann JP, Monetti MS, Frutos MC, Kiguen AX, Venezuela RF, Cuffini CG. Mutation detection of E6 and LCR genes from HPV 16 associated with carcinogenesis. Asian Pac J Cancer Prev. 2015;16(3):1151–7.CrossRef
9.
go back to reference Yang Y, Ren J, Zhang Q. Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer: a case control study in Guizhou Province, China. J Med Virol. 2016;88(2):345–50.CrossRef Yang Y, Ren J, Zhang Q. Distribution of human papilloma virus type 16 E6/E7 gene mutation in cervical precancer or cancer: a case control study in Guizhou Province, China. J Med Virol. 2016;88(2):345–50.CrossRef
10.
go back to reference Cornet I, Gheit T, Franceschi S, Vignat J, Burk RD, Sylla BS, et al. Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. J Virol. 2012;86(12):6855–61.CrossRef Cornet I, Gheit T, Franceschi S, Vignat J, Burk RD, Sylla BS, et al. Human papillomavirus type 16 genetic variants: phylogeny and classification based on E6 and LCR. J Virol. 2012;86(12):6855–61.CrossRef
11.
go back to reference Sun Z, Lu Z, Liu J, Wang G, Zhou W, Yang L, et al. Genetic variations of E6 and long control region of human papillomavirus type16 from patients with cervical lesion in Liaoning, China. BMC Cancer. 2013;13:459.CrossRef Sun Z, Lu Z, Liu J, Wang G, Zhou W, Yang L, et al. Genetic variations of E6 and long control region of human papillomavirus type16 from patients with cervical lesion in Liaoning, China. BMC Cancer. 2013;13:459.CrossRef
12.
go back to reference Gheit T, Cornet I, Clifford GM, Iftner T, Munk C, Tommasino M, et al. Risks for persistence and progression by human papillomavirus type 16 variant lineages among a population-based sample of Danish women. Cancer Epidemiol Prev Biomark. 2011;20(7):1315–21.CrossRef Gheit T, Cornet I, Clifford GM, Iftner T, Munk C, Tommasino M, et al. Risks for persistence and progression by human papillomavirus type 16 variant lineages among a population-based sample of Danish women. Cancer Epidemiol Prev Biomark. 2011;20(7):1315–21.CrossRef
13.
go back to reference Smith B, Chen Z, Reimers L, van Doorslaer K, Schiffman M, DeSalle R, et al. Sequence imputation of HPV16 genomes for genetic association studies. PLoS ONE. 2011;6(6):e21375.CrossRef Smith B, Chen Z, Reimers L, van Doorslaer K, Schiffman M, DeSalle R, et al. Sequence imputation of HPV16 genomes for genetic association studies. PLoS ONE. 2011;6(6):e21375.CrossRef
14.
go back to reference Berumen J, Ordoñez RM, Lazcano E, Salmeron J, Galvan SC, Estrada RA, et al. Asian–American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study. J Natl Cancer Inst. 2001;93(17):1325–30.CrossRef Berumen J, Ordoñez RM, Lazcano E, Salmeron J, Galvan SC, Estrada RA, et al. Asian–American variants of human papillomavirus 16 and risk for cervical cancer: a case-control study. J Natl Cancer Inst. 2001;93(17):1325–30.CrossRef
15.
go back to reference Seedorf K, Krammer G, Durst M, Suhai S, Rowekamp WG. Human papillomavirus type 16 DNA sequence. Virology. 1985;145:181–5.CrossRef Seedorf K, Krammer G, Durst M, Suhai S, Rowekamp WG. Human papillomavirus type 16 DNA sequence. Virology. 1985;145:181–5.CrossRef
16.
go back to reference Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30:2725–9.CrossRef Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol. 2013;30:2725–9.CrossRef
17.
go back to reference Ren J, Zhang Q, Yang Y, et al. Association between D32E/M28V + L94P variant of Human papilloma virus type 16 E6/E7 gene with CIN and the cervical cancer. Chin J Exp Clin Virol. 2015;29(5):417–20. Ren J, Zhang Q, Yang Y, et al. Association between D32E/M28V + L94P variant of Human papilloma virus type 16 E6/E7 gene with CIN and the cervical cancer. Chin J Exp Clin Virol. 2015;29(5):417–20.
18.
go back to reference Cornet I, Gheit T, Iannacone MR, Vignat J, Sylla BS, Del Mistro A, et al. HPV16 genetic variation and the development of cervical cancer worldwide. Br J Cancer. 2013;108(1):240–4.CrossRef Cornet I, Gheit T, Iannacone MR, Vignat J, Sylla BS, Del Mistro A, et al. HPV16 genetic variation and the development of cervical cancer worldwide. Br J Cancer. 2013;108(1):240–4.CrossRef
19.
go back to reference Cai HB, Chen CC, Ding XH. Human papillomavirus type 16 E6 gene variations in Chinese population. Eur J Surg Oncol. 2010;36(2):160–3.CrossRef Cai HB, Chen CC, Ding XH. Human papillomavirus type 16 E6 gene variations in Chinese population. Eur J Surg Oncol. 2010;36(2):160–3.CrossRef
20.
go back to reference Qmichou Z, Khyatti M, Berraho M, Ennaji MM, Benbacer L, Nejjari C, Benjaafar N, Benider A, Attaleb M, El Mzibri M. Analysis of mutations in the E6 oncogene of human papillomavirus 16 in cervical cancer isolates from Moroccan women. BMC Infect Dis. 2013;13:378.CrossRef Qmichou Z, Khyatti M, Berraho M, Ennaji MM, Benbacer L, Nejjari C, Benjaafar N, Benider A, Attaleb M, El Mzibri M. Analysis of mutations in the E6 oncogene of human papillomavirus 16 in cervical cancer isolates from Moroccan women. BMC Infect Dis. 2013;13:378.CrossRef
21.
go back to reference Shang Q, Wang Y, Fang Y, Wei L, Chen S, Sun Y, et al. Human papillomavirus type 16 variant analysis of E6, E7 and L1 genes and long control region in cervical carcinomas in patients in northeast China. J Clin Microbiol. 2011;49(7):2656–63.CrossRef Shang Q, Wang Y, Fang Y, Wei L, Chen S, Sun Y, et al. Human papillomavirus type 16 variant analysis of E6, E7 and L1 genes and long control region in cervical carcinomas in patients in northeast China. J Clin Microbiol. 2011;49(7):2656–63.CrossRef
22.
go back to reference Mi J, Rhee JE, Jang DH, Kim SS. Gene expression profiles are altered in human papillomavirus-16 E6 D25E-expressing cell lines. Virol J. 2011;8(1):1–6.CrossRef Mi J, Rhee JE, Jang DH, Kim SS. Gene expression profiles are altered in human papillomavirus-16 E6 D25E-expressing cell lines. Virol J. 2011;8(1):1–6.CrossRef
23.
go back to reference Chansaenroj J, Theamboonlers A, Junyangdikul P, Swangvaree S, Karalak A, Poovorawan Y. Whole genome analysis of human papillomavirus type 16 multiple infection in cervical cancer patients. Asian Pacific J Cancer Prev. 2012;13(2):599–606.CrossRef Chansaenroj J, Theamboonlers A, Junyangdikul P, Swangvaree S, Karalak A, Poovorawan Y. Whole genome analysis of human papillomavirus type 16 multiple infection in cervical cancer patients. Asian Pacific J Cancer Prev. 2012;13(2):599–606.CrossRef
24.
go back to reference Yang L, Yang H, Kun W, Shi X, Ma S, Sun Q. Prevalence of HPV and variation of HPV16/HPV18 E6/E7 genes in cervical cancer in women in South West China. J Med Virol. 2014;86(11):1926–36.CrossRef Yang L, Yang H, Kun W, Shi X, Ma S, Sun Q. Prevalence of HPV and variation of HPV16/HPV18 E6/E7 genes in cervical cancer in women in South West China. J Med Virol. 2014;86(11):1926–36.CrossRef
25.
go back to reference Jenison SA, Yu XP, Valentine JM, Galloway DA. Characterization of human antibody-reactive epitopes encoded by human papillomavirus types 16 and 18. J Virol. 1991;65(3):1208.PubMedPubMedCentral Jenison SA, Yu XP, Valentine JM, Galloway DA. Characterization of human antibody-reactive epitopes encoded by human papillomavirus types 16 and 18. J Virol. 1991;65(3):1208.PubMedPubMedCentral
26.
go back to reference Youk EG, Ku JL, Park JG. Detection and typing of human papillomavirus in anal epidermoid carcinomas: sequence variation in the E7 gene of human papillomavirus type 16. Dis Colon Rectum. 2001;44(2):236–42.CrossRef Youk EG, Ku JL, Park JG. Detection and typing of human papillomavirus in anal epidermoid carcinomas: sequence variation in the E7 gene of human papillomavirus type 16. Dis Colon Rectum. 2001;44(2):236–42.CrossRef
27.
go back to reference Fujinaga Y, Okazawa K, Nishikawa A, Yamakawa Y, Fukushima M, Kato I, et al. Sequence variation of human papillomavirus type 16 E7 in preinvasive and invasive cervical neoplasias. Virus Genes. 1994;9(1):85–92.CrossRef Fujinaga Y, Okazawa K, Nishikawa A, Yamakawa Y, Fukushima M, Kato I, et al. Sequence variation of human papillomavirus type 16 E7 in preinvasive and invasive cervical neoplasias. Virus Genes. 1994;9(1):85–92.CrossRef
28.
go back to reference Tornesello ML, Duraturo ML, Salatiello I, Buonaguro L, Losito S, Botti G, Stellato G, Greggi S, Piccoli R, Pilotti S, Stefanon B. Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol. 2004;74(1):117–26.CrossRef Tornesello ML, Duraturo ML, Salatiello I, Buonaguro L, Losito S, Botti G, Stellato G, Greggi S, Piccoli R, Pilotti S, Stefanon B. Analysis of human papillomavirus type-16 variants in Italian women with cervical intraepithelial neoplasia and cervical cancer. J Med Virol. 2004;74(1):117–26.CrossRef
29.
go back to reference Ding T, Wang X, Ye F, Cheng X, Lu W, Xie X. Distribution of human papillomavirus 16 E6/E7 variants in cervical cancer and intraepithelial neoplasia in Chinese women. Int J Gynecol Cancer. 2010;20(8):1391–8.PubMed Ding T, Wang X, Ye F, Cheng X, Lu W, Xie X. Distribution of human papillomavirus 16 E6/E7 variants in cervical cancer and intraepithelial neoplasia in Chinese women. Int J Gynecol Cancer. 2010;20(8):1391–8.PubMed
30.
go back to reference Anacker DC, Moody CA. Modulation of the DNA damage response during the life cycle of human papillomaviruses. Virus Res. 2017;231:41–9.CrossRef Anacker DC, Moody CA. Modulation of the DNA damage response during the life cycle of human papillomaviruses. Virus Res. 2017;231:41–9.CrossRef
31.
go back to reference Xi J, Chen J, Xu M, Yang H, Luo J, Pan Y, et al. Genetic variability and functional implication of the long control region in HPV-16 variants in Southwest China. PLoS ONE. 2017;12(8):e0182388.CrossRef Xi J, Chen J, Xu M, Yang H, Luo J, Pan Y, et al. Genetic variability and functional implication of the long control region in HPV-16 variants in Southwest China. PLoS ONE. 2017;12(8):e0182388.CrossRef
Metadata
Title
Genetic variations in E6, E7 and the long control region of human papillomavirus type 16 among patients with cervical lesions in Xinjiang, China
Authors
Xiangyi Zhe
Huizhen Xin
Zhenzhen Pan
Fuyuan Jin
Weinan Zheng
Hongtao Li
Dongmei Li
Dongdong Cao
Ying Li
Chunhe Zhang
Shaowei Fu
Renfu Shao
Zemin Pan
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0774-5

Other articles of this Issue 1/2019

Cancer Cell International 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine