宫颈人乳头瘤病毒感染的转归与阴道微生物菌群相关性研究进展

doi:10.12280/gjszjk.20200544

摘要/Abstract

摘要：

高危型人乳头瘤病毒（HPV）持续感染是宫颈癌前病变及宫颈癌发生的必要条件,其感染与清除受到多种因素影响。阴道微生物菌群在女性下生殖道健康中发挥着重要作用,正常女性阴道微生物多样性低,仅由少数几种乳杆菌（Lactobacillus）构成。随着对细菌16S rRNA基因高通量测序技术的应用,阴道微生物群落结构被深入研究。越来越多的研究证据表明阴道微生物菌群多样性增加、乳杆菌相对丰度减少等阴道菌群组成变化与HPV感染的发生和持续以及宫颈病变的发生发展密切相关。重建以乳杆菌为主的阴道微生物群落结构、恢复阴道微生态平衡能够促进HPV的清除,是未来HPV感染及宫颈病变治疗的新方向。本文讨论宫颈HPV感染的转归与阴道微生物菌群间的相关性。

关键词: 乳头状瘤病毒科, 癌前状态, 宫颈肿瘤, 阴道微生物菌群, 菌群失调

Abstract:

High-risk human papillomavirus (HPV) infection is a requirement of cervical precancerous lesions or cervical cancer. There are many factors that affect the infection and clearance of HPV. Vaginal microflora plays an important role in the health of female lower reproductive tract. A healthy female vaginal microbiome is defined as low diversity, which is dominated by the few species of Lactobacillus. With the application of high-throughput sequencing technology for bacterial 16S rRNA gene, the structure of vaginal microbial community has been further studied. More and more research evidences show that the changes in the composition of the vaginal microflora such as the increase in the diversity of the vaginal microflora and the decrease in the relative abundance of Lactobacillus are closely related to HPV infection and the occurrence and development of cervical lesions. Reconstruction of the vaginal microbial community dominated by Lactobacillus and restoration of the vaginal microecological balance can promote the clearance of HPV. This is a new direction for the treatment of HPV infection and cervical lesions in the future. This review summarizes the correlation between the outcome of cervical HPV infection and the changes in the composition of vaginal microbial flora.

Key words: Papillomaviridae, Precancerous conditions, Uterine cervical neoplasms, Vaginal microflora, Dysbacteriosis

韦莹婷, 邱丽华. 宫颈人乳头瘤病毒感染的转归与阴道微生物菌群相关性研究进展[J]. 国际生殖健康/计划生育, 2021, 40(3): 252-255.

WEI Ying-ting, QIU Li-hua. Research Progress on the Correlation between the Outcome of Cervical HPV Infection and Vaginal Microbiome[J]. Journal of International Reproductive Health/Family Planning, 2021, 40(3): 252-255.

参考文献 36

[1]	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018,68(6):394-424. doi: 10.3322/caac.21492. doi: 10.3322/caac.v68.6 URL
[2]	Roden R, Stern PL. Opportunities and challenges for human papillomavirus vaccination in cancer[J]. Nat Rev Cancer, 2018,18(4):240-254. doi: 10.1038/nrc.2018.13. doi: 10.1038/nrc.2018.13 URL
[3]	de Sanjosé S, Brotons M, Pavón MA. The natural history of human papillomavirus infection[J]. Best Pract Res Clin Obstet Gynaecol, 2018,47:2-13. doi: 10.1016/j.bpobgyn.2017.08.015. doi: S1521-6934(17)30133-5 URL pmid: 28964706
[4]	Cohen PA, Jhingran A, Oaknin A, et al. Cervical cancer[J]. Lancet, 2019,393(10167):169-182. doi: 10.1016/S0140-6736(18)32470-X. doi: S0140-6736(18)32470-X URL pmid: 30638582
[5]	Liang Y, Chen M, Qin L, et al. Correction to: A meta-analysis of the relationship between vaginal microecology, human papillomavirus infection and cervical intraepithelial neoplasia[J]. Infect Agent Cancer, 2019,14:47. doi: 10.1186/s13027-019-0258-1. doi: 10.1186/s13027-019-0258-1 URL
[6]	安瑞芳, 曾宪玲. 阴道微生态诊治的最新进展[J]. 中国实用妇科与产科杂志, 2017,33(8):787-791. doi: 10.19538/j.fk2017080105.
[7]	Chen Y, Qiu X, Wang W, et al. Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort[J]. BMC Infect Dis, 2020,20(1):629. doi: 10.1186/s12879-020-05324-9. doi: 10.1186/s12879-020-05324-9 URL
[8]	Tachedjian G, Aldunate M, Bradshaw CS, et al. The role of lactic acid production by probiotic Lactobacillus species in vaginal health[J]. Res Microbiol, 2017,168(9/10):782-792. doi: 10.1016/j.resmic.2017.04.001. doi: 10.1016/j.resmic.2017.04.001 URL
[9]	Witkin SS, Linhares IM. Why do lactobacilli dominate the human vaginal microbiota?[J]. BJOG, 2017,124(4):606-611. doi: 10.1111/1471-0528.14390. doi: 10.1111/bjo.2017.124.issue-4 URL
[10]	Smith SB, Ravel J. The vaginal microbiota, host defence and reproductive physiology[J]. J Physiol, 2017,595(2):451-463. doi: 10.1113/JP271694. doi: 10.1113/tjp.2017.595.issue-2 URL
[11]	Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women[J]. Proc Natl Acad Sci U S A, 2011,108(Suppl 1):4680-4687. doi: 10.1073/pnas.1002611107. doi: 10.1073/pnas.1002611107 URL
[12]	陈雨莲, 邱丽华, 高华, 等. 阴道微生物与人乳头瘤病毒感染及宫颈上皮内肿瘤相关性研究进展[J]. 国际妇产科学杂志, 2018,45(3):301-305. doi: 10.3969/j.issn.1674-1870.2018.03.016.
[13]	Greenbaum S, Greenbaum G, Moran-Gilad J, et al. Ecological dynamics of the vaginal microbiome in relation to health and disease[J]. Am J Obstet Gynecol, 2019,220(4):324-335. doi: 10.1016/j.ajog.2018.11.1089. doi: 10.1016/j.ajog.2018.11.1089 URL
[14]	Stout MJ, Zhou Y, Wylie KM, et al. Early pregnancy vaginal microbiome trends and preterm birth[J]. Am J Obstet Gynecol, 2017, 217(3): 356.e1-e18. doi: 10.1016/j.ajog.2017.05.030. doi: 10.1016/j.ajog.2017.05.030 URL
[15]	Brotman RM, Shardell MD, Gajer P, et al. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy[J]. Menopause, 2018,25(11):1321-1330. doi: 10.1097/GME.0000000000001236.
[16]	Bradshaw CS, Walker SM, Vodstrcil LA, et al. The influence of behaviors and relationships on the vaginal microbiota of women and their female partners: the WOW Health Study[J]. J Infect Dis, 2014,209(10):1562-1572. doi: 10.1093/infdis/jit664. doi: 10.1093/infdis/jit664 URL
[17]	van der Veer C, Bruisten SM, van Houdt R, et al. Effects of an over-the-counter lactic-acid containing intra-vaginal douching product on the vaginal microbiota[J]. BMC Microbiol, 2019,19(1):168. doi: 10.1186/s12866-019-1545-0. doi: 10.1186/s12866-019-1545-0 URL pmid: 31345159
[18]	贾绍月, 钟莉春, 杨红文, 等. 宫颈上皮内瘤变患者HPV感染情况及转阴率的相关因素分析[J]. 中国性科学, 2017,26(11):43-46. doi: 10.3969/j.issn.1672-1993.2017.11.013.
[19]	龙馨, 杨君, 周德平, 等. 2784例同步HPV分型及标准化定量检测预测高危型HPV感染转归的临床研究[J]. 第三军医大学学报, 2020,42(15):1555-1561. doi: 10.16016/j.1000-5404.202003322.
[20]	宋建东, 宋静慧, 于聪祥, 等. 影响宫颈病变患者HPV转归的多因素分析[J]. 中国实用妇科与产科杂志, 2018,34(8):892-897. doi: 10.19538/j.fk2018080116.
[21]	Brotman RM, Shardell MD, 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. doi: 10.1093/infdis/jiu330. doi: 10.1093/infdis/jiu330 URL
[22]	Mitra A, MacIntyre DA, Ntritsos G , et al. The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions[J]. Nat Commun, 2020,11(1):1999. doi: 10.1038/s41467-020-15856-y. doi: 10.1038/s41467-020-15856-y URL
[23]	Anahtar MN, Byrne EH, Doherty KE, et al. Cervicovaginal bacteria are a major modulator of host inflammatory responses in the female genital tract[J]. Immunity, 2015,42(5):965-976. doi: 10.1016/j.immuni.2015.04.019. doi: 10.1016/j.immuni.2015.04.019 URL pmid: 25992865
[24]	Curty G, de Carvalho PS, Soares MA. The Role of the Cervicovaginal Microbiome on the Genesis and as a Biomarker of Premalignant Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer[J]. Int J Mol Sci, 2019,21(1):222. doi: 10.3390/ijms21010222. doi: 10.3390/ijms21010222 URL
[25]	Lee JE, 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. doi: 10.1371/journal.pone.0063514. doi: 10.1371/journal.pone.0063514 URL
[26]	Di Paola M, Sani C, Clemente AM, et al. Characterization of cervico-vaginal microbiota in women developing persistent high-risk Human Papillomavirus infection[J]. Sci Rep, 2017,7(1):10200. doi: 10.1038/s41598-017-09842-6. doi: 10.1038/s41598-017-09842-6 URL
[27]	Zhang C, Liu Y, Gao W, et al. The direct and indirect association of cervical microbiota with the risk of cervical intraepithelial neoplasia[J]. Cancer Med, 2018,7(5):2172-2179. doi: 10.1002/cam4.1471. doi: 10.1002/cam4.2018.7.issue-5 URL
[28]	Godoy-Vitorino F, Romaguera J, Zhao C, et al. Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population[J]. Front Microbiol, 2018,9:2533. doi: 10.3389/fmicb.2018.02533. doi: 10.3389/fmicb.2018.02533 URL pmid: 30405584
[29]	Piyathilake CJ, Ollberding NJ, Kumar R, et al. Cervical Microbiota Associated with Higher Grade Cervical Intraepithelial Neoplasia in Women Infected with High-Risk Human Papillomaviruses[J]. Cancer Prev Res(Phila), 2016,9(5):357-366. doi: 10.1158/1940-6207.CAPR-15-0350.
[30]	Norenhag J, Du J, Olovsson M, et al. The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis[J]. BJOG, 2020,127(2):171-180. doi: 10.1111/1471-0528.15854. doi: 10.1111/bjo.v127.2 URL
[31]	Wang KD, Xu DJ, Wang BY, et al. Inhibitory Effect of Vaginal Lactobacillus Supernatants on Cervical Cancer Cells[J]. Probiotics Antimicrob Proteins, 2018,10(2):236-242. doi: 10.1007/s12602-017-9339-x. doi: 10.1007/s12602-017-9339-x URL
[32]	Palma E, Recine N, Domenici L, et al. Long-term Lactobacillus rhamnosus BMX 54 application to restore a balanced vaginal ecosystem: a promising solution against HPV-infection[J]. BMC Infect Dis, 2018,18(1):13. doi: 10.1186/s12879-017-2938-z. doi: 10.1186/s12879-017-2938-z URL
[33]	Collins SL, McMillan A, Seney S , et al. Promising Prebiotic Candidate Established by Evaluation of Lactitol, Lactulose, Raffinose, and Oligofructose for Maintenance of a Lactobacillus-Dominated Vaginal Microbiota[J]. Appl Environ Microbiol, 2018,84(5):e02200-17. doi: 10.1128/AEM.02200-17.
[34]	Zhang H, Lu J, Lu Y, et al. Cervical microbiome is altered in cervical intraepithelial neoplasia after loop electrosurgical excision procedure in china[J]. Sci Rep, 2018,8(1):4923. doi: 10.1038/s41598-018-23389-0. doi: 10.1038/s41598-018-23389-0 URL
[35]	康玲, 马啸, 蔡慧华, 等. 高级别宫颈鳞状上皮内瘤变锥切手术前后阴道菌群比较研究[J]. 中国实用妇科与产科杂志, 2017,33(9):949-954. doi: 10.19538/j.fk2017090117.
[36]	陈忆, 李柱南, 张峥嵘, 等. 阴道用乳杆菌活菌胶囊在宫颈癌前病变LEEP术后应用价值的临床研究[J]. 中国微生态学杂志, 2018,30(7):832-835. doi: 10.13381/j.cnki.cjm.201807020.