Xu Hui-Hui, Zheng Ling-Zhi, Lin Ai-Fen, Dong Shan-Shan, Chai Ze-Ying, Yan Wei-Hua
Laboratory of Gynecologic Oncology, Medical Research Center, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China.
Department of Gynecology and Obstetrics, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, China.
Gene. 2018 Mar 20;647:192-197. doi: 10.1016/j.gene.2018.01.037. Epub 2018 Jan 10.
Human papillomavirus (HPV) type 18 is predominantly associated with the development of cervical adenocarcinomas, whereas data on HPV18 genetic variability in China are limited. HPV18 genetic variants were formed phylogenetic tree, including lineages A, B, and C. We aimed to evaluate the diversity of HPV18 genetic variants by sequencing the entire E6, E7 and L1 genes. Between 2012 and 2015, a total of 138 (0.8%, 138/17669) women with single HPV18 infection were selected in this study. Finally, we observed 122 HPV18 isolates of the complete E6-E7-L1 sequences, and obtained 36 distinct variation patterns which the accession GenBank numbers as KY457805-KY457840. Except KY457805, KY457813, KY457819, KY457827, KY457829, the rest of HPV18 isolates (81.1%, 31/36) are novel variants. All of HPV18 variants belong to lineage A, while no lineage B, and C was found in our population of Taizhou region, Southeast China. Sublineage A1 was the most common variants (85.2%, 104/122), followed by sublineage A4, A3 and A5, while no sublineage A2 was obtained. Based on the tree topologies, there were three newly identified candidates' sublineages A6-A8. Out of 122 women, 67 (54.9%) had diagnosed by biopsy, including 49 women who diagnosed with cervicitis, 12 with cervical intraepithelial neoplasia (CIN)1, 4 with CIN2/3, and 2 with adenocarcinomas, respectively. Nevertheless, there was no association between HPV18 (sub) lineages and CIN1 or worse (CIN1+) lesions comparing with normal biopsies (P = .469). In conclusion, knowledge of the distribution of geographic/ethnical HPV18 genetic diversity provides critical information for developing diagnostic probes, epidemiologic correlate of cervical cancer risk and design of HPV vaccines for targeted populations.
18型人乳头瘤病毒（HPV）主要与宫颈腺癌的发生相关，而中国关于HPV18基因变异性的数据有限。HPV18基因变异形成了系统发育树，包括A、B和C谱系。我们旨在通过对整个E6、E7和L1基因进行测序来评估HPV18基因变异的多样性。2012年至2015年期间，本研究共选取了138例（0.8%，138/17669）单一HPV18感染的女性。最终，我们观察到122株HPV18完整E6-E7-L1序列的分离株，并获得了36种不同的变异模式，其GenBank登录号为KY457805-KY457840（原文此处表述有误，应为KY457805-KY457840）。除KY457805、KY457813、KY457819、KY457827、KY457829外，其余HPV18分离株（81.1%）为新变异株。所有HPV18变异株均属于A谱系，在中国东南部台州地区人群中未发现B和C谱系。A1亚谱系是最常见的变异株（85.2%，104/122），其次是A4、A3和A5亚谱系，未获得A2亚谱系。基于系统发育树拓扑结构，新鉴定出了三个候选亚谱系A6-A8。在122名女性中，67名（54.9%）经活检确诊，其中49名诊断为宫颈炎，12名诊断为宫颈上皮内瘤变（CIN）1级，4名诊断为CIN2/3级，2名诊断为腺癌。然而，与正常活检相比，HPV18（亚）谱系与CIN1或更严重（CIN1+）病变之间无关联（P = 0.469）。总之，了解地理/种族HPV18基因多样性的分布为开发诊断探针、宫颈癌风险的流行病学关联以及针对特定人群的HPV疫苗设计提供了关键信息。
