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中国宫颈鳞状上皮内瘤变患者阴道微生物组特征。

Characterization of vaginal microbiota in Chinese women with cervical squamous intra-epithelial neoplasia.

机构信息

Clinical Laboratory, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.

出版信息

Int J Gynecol Cancer. 2020 Oct;30(10):1500-1504. doi: 10.1136/ijgc-2020-001341. Epub 2020 Jun 3.

DOI:10.1136/ijgc-2020-001341
PMID:32499394
Abstract

OBJECTIVES

Although persistent human papillomavirus (HPV) infection is a major cause of cervical squamous intra-epithelial neoplasia, the relationship between vaginal microbiota and different grades of squamous intra-epithelial neoplasia is not well established. We explored the possible relationship between the vaginal microbiota and the progression of cervical squamous intra-epithelial neoplasia.

METHODS

We evaluated 69 women who attended the Obstetrics and Gynecology Hospital of Fudan University. The vaginal bacterial composition of three groups of women was characterized by deep sequencing of bar-coded 16S rRNA gene fragments (V3-4) using Illumina MiSeq. Exclusion criteria were any previous hysterectomy, history of cervical or other lower genital cancer, and/or destructive therapy of the cervix. Women who had autoimmune disorders, who were HIV positive, who received antibiotics within 15 days of sampling, or who had engaged in sexual intercourse or douching within 48 hours prior to sampling were also excluded. P values for age and proportions of organisms were calculated using one-way ANOVA and p values for HPV status and community state types (CSTs) were calculated using a χ test.

RESULTS

The vaginal bacterial composition of three groups of women, those without an intra-epithelial lesion or malignancy (n=31), those with a low-grade squamous intra-epithelial lesion (LSIL) (n=22), and those with a high-grade squamous intra-epithelial lesion (HSIL) (n=16) were analyzed. was the most dominant genus overall. and were increased in the HSIL group. Cervical disease progression was associated with the prevalence of high-risk HPV infection. Squamous intra-epithelial neoplasia converted the vaginal bacterial community structure from CSTs IV to II. Microbiota diversity was more pronounced in CST types II and IV (p<0.001), especially in type II. We found a significant enrichment in the Peptostreptococcaceae family, Pseudomonadales order, and other types of bacteria in the group of women without intra-epithelial lesions or malignancy compared with women with squamous intra-epithelial neoplasia. We found enrichment in in the LSIL and HSIL groups compared with the group without an intra-epithelial lesion or malignancy.

CONCLUSIONS

Our results show that the vaginal microbiota is directly or indirectly related to the progression of squamous intra-epithelial neoplasia, and might be a microbiological hallmark of cervical pre-cancerous lesions.

摘要

目的

尽管持续性人乳头瘤病毒(HPV)感染是宫颈鳞状上皮内瘤变的主要原因,但阴道微生物群与不同级别鳞状上皮内瘤变之间的关系尚未得到很好的确定。我们探讨了阴道微生物群与宫颈鳞状上皮内瘤变进展之间的可能关系。

方法

我们评估了 69 名就诊于复旦大学妇产科医院的女性。通过 Illumina MiSeq 对三组女性的阴道细菌组成进行了 16S rRNA 基因片段(V3-4)的条形码深度测序。排除标准为任何先前的子宫切除术、宫颈或其他下生殖道癌症病史和/或宫颈破坏性治疗。排除自身免疫性疾病、HIV 阳性、采样前 15 天内使用抗生素或采样前 48 小时内有性行为或阴道冲洗的女性。使用单向方差分析计算年龄和生物体比例的 P 值,使用 χ 检验计算 HPV 状态和社区状态类型(CSTs)的 P 值。

结果

分析了三组女性的阴道细菌组成,即无上皮内病变或恶性肿瘤的女性(n=31)、低级别鳞状上皮内病变(LSIL)的女性(n=22)和高级别鳞状上皮内病变(HSIL)的女性(n=16)。 总体上是最主要的属。HSIL 组中 和 的含量增加。宫颈疾病的进展与高危 HPV 感染的流行有关。鳞状上皮内瘤变将阴道细菌群落结构从 CSTs IV 转变为 CSTs II。CST 类型 II 和 IV 的微生物多样性更为明显(p<0.001),尤其是在 CST 类型 II 中。与无上皮内病变或恶性肿瘤的女性相比,我们发现无上皮内病变或恶性肿瘤的女性组中 Peptostreptococcaceae 科、假单胞菌目和其他类型的细菌显著富集。与无上皮内病变或恶性肿瘤的女性相比,我们发现 LSIL 和 HSIL 组中 富集。

结论

我们的结果表明,阴道微生物群与鳞状上皮内瘤变的进展直接或间接相关, 可能是宫颈癌前病变的微生物学标志。

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