Yang Qian, Wang Yaping, Wei Xinyi, Zhu Jiawei, Wang Xinyu, Xie Xing, Lu Weiguo
Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Gynecologic Oncology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Cell Infect Microbiol. 2020 Jun 23;10:286. doi: 10.3389/fcimb.2020.00286. eCollection 2020.
The association of microbiome imbalance with cancer development is being one of the research hotspots. Persistent HPV infection is a causal event in cervical cancer initiation, but, little is known about the microbiome composition and function in HPV infection. Here we identified the compositional and functional alterations on vaginal samples from 27 HPV16 positive women and 25 age-matched HPV negative controls using shotgun metagenomic sequencing, to provide a comprehensive investigation describing the microbial abundances and enriched metabolic functions in cervicovaginal metagenomes. We further employed qPCR assays to evaluate two selected gene markers of HPV16 infection in an independent validation cohort consisting of 88 HPV16 positive women and 81 controls, and six selected species markers in a subset of validation cohort of 45 HPV16 positive women and 53 controls. We found that the relative abundance of dominant Firmicutes was lower, Actinobacteria, Fusobacteria and viruses phyla were significantly higher in the HPV16-positive group; 77 genera including , and were higher, and 20 genera including and were lower in the HPV16-positive women. Abundance of 12 genes, 17 genera, and 7 species biomarkers showed an excellent predictive power for the HPV16-positive individuals, with 0.861, 0.819, and 0.918, respectively, of the area under the receiver-operating characteristic curve (AUC). We further characterized the microbial function, and revealed that HPV16-positive women were enriched in metabolism and membrane transport, and depleted by glycan biosynthesis and metabolism, and replication and repair. Quantitative PCR measurements validated that one gene marker and three species were significantly enriched in HPV16-positive women. These results highlight a fundamental fact that there are altered composition and function of the vaginal microbiome in HPV16-positive women, suggesting that vaginal dysbiosis may be associated with HPV infection in the female genital tract.
微生物群失衡与癌症发展之间的关联一直是研究热点之一。持续性人乳头瘤病毒（HPV）感染是宫颈癌发生的一个因果事件，但对于HPV感染中的微生物群组成和功能却知之甚少。在此，我们使用鸟枪法宏基因组测序鉴定了27名HPV16阳性女性和25名年龄匹配的HPV阴性对照者阴道样本中的组成和功能变化，以全面研究宫颈阴道宏基因组中的微生物丰度和富集的代谢功能。我们进一步采用定量聚合酶链反应（qPCR）分析，在一个由88名HPV16阳性女性和81名对照组成的独立验证队列中评估HPV16感染的两个选定基因标志物，并在一个由45名HPV16阳性女性和53名对照组成的验证队列子集中评估六个选定的物种标志物。我们发现，HPV16阳性组中优势厚壁菌门的相对丰度较低，放线菌门、梭杆菌门和病毒门显著较高；在HPV16阳性女性中，包括……等在内的77个属较高，包括……等在内的20个属较低。12个基因、17个属和7个物种生物标志物的丰度对HPV16阳性个体显示出优异的预测能力，受试者工作特征曲线（AUC）下面积分别为0.861、0. .819和0.918。我们进一步对微生物功能进行了表征，发现HPV16阳性女性在代谢和膜转运方面富集，而在聚糖生物合成与代谢以及复制和修复方面减少。定量PCR测量验证了一个基因标志物和三个物种在HPV16阳性女性中显著富集。这些结果突出了一个基本事实，即HPV16阳性女性的阴道微生物群组成和功能发生了改变，表明阴道生态失调可能与女性生殖道中的HPV感染有关。
