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

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

doi:10.1186/s12935-019-0774-5

Abstract

BackgroundXinjiang 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.MethodsA 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.ResultsFourteen 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.ConclusionHPV16 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.

Highlights

Xinjiang is one of the areas with the highest incidence of cervical cancer in China
We explored the relationships between Human papillomavirus type 16 (HPV16) E6, E7, and long control region (LCR) gene mutations and the incidence of cervical cancer in Xinjiang, to accumulate molecular epidemiological data for the study of HPV16 gene polymorphism in cervical lesions
Mutation analysis of HPV16 E6, E7 and LCR genes In total, 138 HPV16 positive samples were sequenced to give full-length HPV16 LCR sequences, and 90 cases were chosen to carry out full-length HPV16 E6 and E7 gene sequencing

Summary

Introduction

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. The integration and mutation of E1 and E2 may promote the expression of virus genes E6 and E7, leading to the occurrence and development of cervical cancer [5]. Many researchers have sequenced the HPV16 genes isolated from cervical lesions. It has been found that the variation in HPV16 E6 and E7 is correlated with the progression of cervical lesions and that HPV16 variant and HPV16 E6 and E7 mutations vary by racial and geographic area [7,8,9]

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