Wang Jiao, Guo Yifan, Wang Hui, Li Ying, Zhang Li, Wang Zhan, Song Lei, Liu Hongtu
Department of Tumor-Associated Virus, National Institute for Viral Disease Control and Prevention, Beijing, 102206, China.
Department of Obstetrics and Gynaecology, Hainan Hospital of Chinese PLA General Hospital, Sanya, 572013, Hainan Province, China.
Biochem Biophys Rep. 2022 May 29;31:101286. doi: 10.1016/j.bbrep.2022.101286. eCollection 2022 Sep.
High-risk human papillomavirus type 16 (HPV16) is a risk factor for cervical cancer. The progression from initial infection to cervical cancer has been linked to properties of the viral sequences. However, the distribution of HPV16 variants among Chinese women has not been extensively addressed and the role of HPV16 variants in the risk of cervical carcinogenesis remains poorly understood.
HPV16 positive cervical exfoliated cell samples were collected from 249 women living in Beijing, China. PCR products from two fragments of E6-E7 and LCR of HPV16 in these samples were sequenced and analyzed.
Lineage A was found in the subjects, including A1, A2, A3 and A4 sublineages. Based on the HPV16 reference sequences, 26 nucleotide mutations of A4 sublineage and 39 nucleotide mutations of A1-3 sublineages were found in the E6, E7 and LCR of HPV16 isolates. Point mutations T843C, A7287C and A7872G of A4 sublineage were significantly associated with high-grade cervical lesions. The high-frequency sites in HPV16 LCR located at regions that can bind to multiple transcription factors.
This study contributes to the identification of unique variants in the E6, E7 and LCR of HPV16 isolates infected in Chinese women. Mutations of T843C, A7287C and A7872G in A4 sublineages were significantly associated with high-grade cervical lesions, suggesting that mutations in the E7 and LCR region have potential effects on viral replication and progression of cervical cancer.
高危型人乳头瘤病毒16型（HPV16）是宫颈癌的一个风险因素。从初始感染到宫颈癌的进展与病毒序列的特性有关。然而，HPV16变体在中国女性中的分布尚未得到广泛研究，HPV16变体在宫颈癌发生风险中的作用仍知之甚少。
从居住在中国北京的249名女性中收集HPV16阳性宫颈脱落细胞样本。对这些样本中HPV16的E6-E7和LCR两个片段的PCR产物进行测序和分析。
在受试者中发现了A谱系，包括A1、A2、A3和A4亚谱系。基于HPV16参考序列，在HPV16分离株的E6、E7和LCR中发现了A4亚谱系的26个核苷酸突变以及A1-3亚谱系的39个核苷酸突变。A4亚谱系的点突变T843C、A7287C和A7872G与高级别宫颈病变显著相关。HPV16 LCR中的高频位点位于可与多种转录因子结合的区域。
本研究有助于鉴定中国女性感染的HPV16分离株在E6、E7和LCR中的独特变体。A4亚谱系中的T843C、A7287C和A7872G突变与高级别宫颈病变显著相关，表明E7和LCR区域的突变对病毒复制和宫颈癌进展具有潜在影响。
