阴道微生物菌群与高危型人乳头瘤病毒16和18型感染的相关性研究

doi:10.3969/j.issn.1006-7795.2018.06.011

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (6): 849-857.doi: 10.3969/j.issn.1006-7795.2018.06.011

• 生殖道HPV感染与宫颈病变 • 上一篇下一篇

阴道微生物菌群与高危型人乳头瘤病毒16和18型感染的相关性研究

罗美¹, 何鑫¹, 刘军¹, 张雪芳¹, 张健欣¹, 王秋曦, 王淑珍, 刁小莉, 曲久鑫³

1. 首都医科大学附属北京朝阳医院妇产科, 北京 100020;
2. 首都医科大学附属北京朝阳医院病理科, 北京 100020;
3. 首都医科大学附属北京朝阳医院检验科, 北京 100020

收稿日期:2018-09-30 出版日期:2018-11-21 发布日期:2018-12-19
通讯作者: 王淑珍 E-mail:darrywang2003@163.com,
基金资助:
北京市自然科学基金（7122069），北京市科学技术委员会科技计划（Z131100004013018）。

Prevalent HPV 16 and 18 infection and vaginal microbiota in initial screening women

Luo Mei¹, He Xin¹, Liu Jun¹, Zhang Xuefang¹, Zhang Jianxin¹, Wang Qiuxi, Wang Shuzhen, Diao Xiaoli, Qu Jiuxin³

1. Department of Gynaecology and Obstetrics, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China;
2. Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China;
3. Department of Laboratory, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

Received:2018-09-30 Online:2018-11-21 Published:2018-12-19
Supported by:
This study was supported by Natural Science Foundation of Beijing(7122069), Scientific Project of Beijing Municipal Science and Technology Committee (Z131100004013018).

摘要/Abstract

摘要： 目的探讨阴道微生物（vaginal microbiota， VMB）组成与人乳头瘤病毒（human papilloma virus， HPV） 16型和18型感染的关系。方法采用基因二代测序方法测定阴道微生物16S rRNA 基因及聚合酶链反应技术（polymerase chain reaction，PCR）进行HPV 16型、18型核酸测定。采用χ²检验及Logistic 回归分析阴道微生物菌群构成类型（community state types，CSTs）与HPV-16型和18型感染的相关性， UniFrac加权矩阵及LEfSe线性分析特定微生物菌群与HPV-16型和18型感染的相关性。结果本研究中共发现3种阴道微生物菌群构成类型，分别是CST IV（low Lactobacillus spp.） 65.4%，CST Ⅲ（L. iners） 32.1%和CST V（L. jensenii） 2.6%，LEfSe分析显示HPV16感染者阴道微生物乳酸杆菌缺乏而厌氧菌属丰富，无乳链球菌（Streptococcus agalactiae）仅发现于HPV16感染者阴道微生物菌群中。HPV18感染者阴道微生物菌群以乳酸杆菌属（Lactobacillus）为主要丰度，而缺乏厌氧菌属。结论阴道微生物菌群的构成及丰度与HPV16感染相关，无乳链球菌可能作为HPV16感染的标志性阴道微生物菌群，但需要进一步研究证据支持。

关键词: 人乳头瘤病毒, 阴道微生物, 宫颈上皮内瘤变, 基因二代测序

Abstract: Objective To evaluate the association between human papillomavirus (HPV) 16, 18 and the vaginal microbiome. Methods Totally 78 women who underwent initial HPV screening in Beijing Chaoyang Hospital between January and June in 2016 were recruited into this study. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Shanghai ZJ Bio-tech Array © HPV genotyping test. The exact Logistic regression models were applied to evaluate the association between community state types (CSTs) of vaginal microbiota and HR-HPV infection, weighted UniFrac distances were used to compare the vaginal microbiota of individuals with prevalent HR-HPV to those without prevalent HR-HPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm was applied to characterize bacteria associated with prevalent HR-HPV infection. Results Three CSTs were observed:CST IV with a low relative abundance of low Lactobacillus spp. in 65.4% of participants; CST Ⅲ(dominated by L. iners) in 32.1%; CST V(dominated by L. jensenii) in 2.6%; LEfSe analysis suggested an association between the prevalent HPV-16 infection and the decreased abundance of Lactobacillus spp. with increased abundance of anaerobes particularly of the genera Streptococcus agalactiae which were only found in HPV-16 positive women (P<0.05). A predominance of Lactobacillus spp. was still present in HPV-18 positive women with depletion of strictly anaerobic species. ConclusionHPV-16 infection was associated with the composition and abundance of vaginal microflora and Streptococcus agalactiae can be the specific bacterial taxa of HPV-16 positive women, Further studies were needed to confirm these finding.

Key words: human papilloma virus, vaginal microbiota, cervical intraepithelial neoplasias, Illumina MiSeq

中图分类号:

R737.33

罗美, 何鑫, 刘军, 张雪芳, 张健欣, 王秋曦, 王淑珍, 刁小莉, 曲久鑫. 阴道微生物菌群与高危型人乳头瘤病毒16和18型感染的相关性研究[J]. 首都医科大学学报, 2018, 39(6): 849-857.

Luo Mei, He Xin, Liu Jun, Zhang Xuefang, Zhang Jianxin, Wang Qiuxi, Wang Shuzhen, Diao Xiaoli, Qu Jiuxin. Prevalent HPV 16 and 18 infection and vaginal microbiota in initial screening women[J]. Journal of Capital Medical University, 2018, 39(6): 849-857.

参考文献

[1] Bosch F X, Lorincz A, Munoz N,et al. The causal relation between human papillomavirus and cervical cancer[J]. J Clin Pathol, 2002, 55(4):244-265.
[2] Kjaer S K, van den Brule A J, Paull G, et al. Type specific persistence of high risk human papillomavirus(HPV) as indicator of high grade cervical squamous intraepithelial lesions in young women:population based prospective follow-up study[J]. BMJ, 2002, 325(7364):572-578.
[3] Lorincz A T, Reid R, Jensen A B, et al. Human papillomavirus infection of the cervix:relative risk associations of 15 common anogenital types[J]. Obstet Gynecol, 1992, 79(3):328-337.
[4] Shew M L, Ermel A C, Tong Y, et al. Episodic detection of human papillomavirus within a longitudinal cohort of young women[J].J Med Virol, 2015, 87(12):2122-2129.
[5] Woodman C B, Collins S, Winter H, et al. Natural history of cervical human papillomavirus infection in young women:a longitudinal cohort study[J]. Lancet, 2001, 357(9271):1831-1836.
[6] Münger K, Baldwin A, Edwards K M, et al. Mechanisms of human papillomavirus-induced oncogenesis[J]. J Virol, 2004, 78(21):11451-11460.
[7] McBride A A, Oliveira J G, McPhillips M G. Partitioning viral genomes in mitosis:same idea, different targets[J]. Cell Cycle, 2006, 5(14):1499-1502.
[8] Bouvard V, Baan R, Straif K, et al. A review of human carcinogens. Part B. Biological agents[J]. Lancet Oncol, 2009, 10(4):321-322.
[9] Lundberg D S, Yourstone S, Mieczkowski P, et al. Practical innovations for high-throughput amplicon sequencing[J]. Nat Methods, 2013, 10(10):999-1002.
[10] Caporaso J G, Lauber C L, Walters W A. Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample[J]. Proc Nat Acad Sci USA, 2011, 108 Suppl:4516-4522.
[11] Srinivasan S, Hoffman N G, Morgan M T, et al. Bacterial communities in women with bacterial vaginosis:high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria[J]. PLoS One, 2012, 7(6):e37818.
[12] Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women[J]. Proc Natl Acad Sci USA,2011, 108 Suppl:4680-4687.
[13] Rajamanoharan S, Low N, Jones S B, et al. Bacterial vaginosis, ethnicity, and the use of genital cleaning agents:a case control study[J]. Sex Transm Dis, 1999, 26(7):404-409.
[14] Gajer P, Brotman R M, Bai G, et al. Temporal dynamics of the human vaginal microbiota[J]. Sci Transl Med, 2012,4(132):132ra52.
[15] MacIntyre D A, Chandiramani M, Lee Y S, et al. The vaginal microbiome during pregnancy and the postpartum period in a European population[J]. Sci Rep, 2015, 5:289-296.
[16] Lee J E, Lee S, Lee H, et al. Association of the vaginal microbiota with human papillomavirus infection in a Korean twin cohort[J]. PLoS One, 2013, 8(5):e63514.
[17] Gao W, Weng J, Gao Y, et al. Comparison of the vaginal microbiota diversity of women with and without human papillomavirus infection:a cross-sectional study[J]. BMC Infect Dis, 2013, 13:271-285.
[18] Brotman R M, Shardell M D, Gajer P, et al. Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection[J]. J Infect Dis, 2014, 210(11):1723-1733.
[19] Dareng E O, Ma B, Famooto A O, et al. Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women[J]. Epidemiol Infect, 2016, 144(1):123-137.
[20] Ryan K J, Ray C G, eds. Sherris medical microbiology[M]. 4th ed. New York:McGraw Hill, 2004:293-294.
[21] Harwich M D Jr., Alves J M, Buck G A, et al. Drawing the line between commensal and pathogenic Gardnerella vaginalis through genome analysis and virulence studies[J]. BMC Genomics, 2010, 11:375.
[22] Gillet E, Meys J F, Verstraelen H, et al. Bacterial vaginosis is associated with uterine cervical human papillomavirus infection:a meta-analysis[J]. BMC Infect Dis, 2011, 11:10.
[23] 王丽丽,王莉.HPV基因分型与宫颈组织病变的相关性研究[J].中华肿瘤防治杂志,2016,23(S1):180-181.
[24] 宋晓玲,蔡红兵.HPV16-E6-DNA对宫颈癌预后预测价值分析[J].中华肿瘤防治杂志,2015,22(6):416-420.
[25] Liu S H, Cummings D A, Zenilman J M, et al. Characterizing the temporal dynamics of human papillomavirus DNA detectability using short-interval sampling[J]. Cancer Epidemiol Biomarkers Prev, 2014, 23(1):200-208.

阴道微生物菌群与高危型人乳头瘤病毒16和18型感染的相关性研究

Prevalent HPV 16 and 18 infection and vaginal microbiota in initial screening women

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王剑磊, 朱天, 韩玉, 王月, 汶春苗, 位嘉. 男性尖锐湿疣患者人乳头瘤病毒基因型分布特点及复发危险因素[J]. 首都医科大学学报, 2023, 44(1): 148-153.
[2]	王俊飞, 沈树娜, 祝平. 液基薄层细胞学检查联合人乳头瘤病毒E6/E7 mRNA检测在宫颈病变筛查中的价值分析[J]. 首都医科大学学报, 2019, 40(4): 578-581.
[3]	黄文阳, 何鑫, 李卫华, 张雪芳, 李湛, 谷丽, 路军丽, 王淑珍. 孕期高危型人乳头瘤病毒的流行病学特征及对妊娠结局的影响[J]. 首都医科大学学报, 2018, 39(6): 836-840.
[4]	张雪芳, 何鑫, 黄文阳, 李卫华, 罗美, 张阳, 王淑珍. 中国女性宫颈高危型HPV感染与阴道微生态关系的Meta分析[J]. 首都医科大学学报, 2018, 39(6): 841-848.
[5]	刘军, 张雪芳, 罗美, 张阳, 王秋曦, 张健欣, 王淑珍. 宫颈脱落细胞学阴性生殖道高危型人乳头瘤病毒阳性患者的临床病理特征[J]. 首都医科大学学报, 2018, 39(6): 858-863.
[6]	张阳, 罗美, 何鑫, 蒋英, 李卫华, 张雪芳, 王淑珍. 高级别宫颈上皮内瘤变及早期宫颈癌子宫切除术后患者高危型人乳头瘤病毒消退规律及相关因素分析[J]. 首都医科大学学报, 2018, 39(6): 864-870.
[7]	张俊俊, 王焱, 杜趁香, 晋熙梦. 脑特异性血管抑制因子-1在宫颈鳞癌中的表达及其与人乳头瘤病毒感染的关系[J]. 首都医科大学学报, 2018, 39(4): 569-574.
[8]	周丽红, 贺昕红, 龙燕, 蔺莉. HTERC基因在宫颈上皮内瘤样病变治疗后监测的相关性研究[J]. 首都医科大学学报, 2015, 36(6): 946-952.
[9]	吕虹, 康熙雄, 张国军. 人乳头瘤病毒基因分型检测在30岁以下年轻妇女宫颈病变中的应用价值[J]. 首都医科大学学报, 2015, 36(4): 588-591.
[10]	何鑫, 陶绘丞, 王淑珍, 朱志清, 王跃, 刁小莉, 曲久鑫. 高危型人乳头瘤病毒阴性/不典型鳞状细胞和低度鳞状上皮内病变患者的随访观察[J]. 首都医科大学学报, 2015, 36(2): 205-211.
[11]	何鑫, 陶绘丞, 刘晨, 王淑珍, 王跃, 刁小莉, 曲久鑫. 医院机会性筛查人群HR-HPV感染的流行病学特征及与宫颈癌前病变的关系[J]. 首都医科大学学报, 2015, 36(2): 219-225.
[12]	刘英俏, 何鑫, 刘军, 王淑珍, 胥莎莎, 王跃, 刁小莉. 宫颈脱落细胞CA-IX的表达与高危型人乳头瘤病毒感染状态的相关性研究[J]. 首都医科大学学报, 2015, 36(2): 226-231.
[13]	何玥;吴玉梅;赵群;王晓丽;陈硕;钱小红;张玉祥. 宫颈上皮内瘤变与正常宫颈组织差异表达蛋白分析[J]. 首都医科大学学报, 2012, 33(1): 36-44.
[14]	殷秀琴;王小菊;赵俊英;刘岩. 液基细胞学检测及阴道镜检查诊断宫颈病变的临床意义[J]. 首都医科大学学报, 2007, 28(5): 658-660.
[15]	赵桂君;蔺莉. 766例宫颈病变临床诊断方法的分析[J]. 首都医科大学学报, 2005, 26(5): 607-611.