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 Gardnerella, Peptostreptococcus, and Prevotella were higher, and 20 genera including Lactobacillus and Aerococcus 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.

微生物组失衡与癌症发展的关系是研究热点之一。持续性HPV感染是宫颈癌发病的起因，但​​对于HPV感染中的微生物组组成和功能知之甚少。在这里，我们使用shot弹枪宏基因组测序确定了来自27位HPV16阳性女性和25位年龄相匹配的HPV阴性对照的阴道样本的成分和功能改变，以提供全面的研究，描述宫颈阴道基因组中的微生物丰度和丰富的代谢功能。我们进一步在独立的验证队列中使用qPCR测定法评估了HPV16感染的两个选定基因标记，该队列由88名HPV16阳性女性和81名对照组成，在45名HPV16阳性女性和53名对照的验证队列中，选择了6种选定的物种标记。我们发现，HPV16阳性组显性优势纤毛虫的相对丰度较低，放线菌，融合细菌和病毒门明显较高；77属包括加德纳氏菌，消化链球菌和 小球藻 更高，包括20个属 乳杆菌 和 气球菌在HPV16阳性女性中较低。12个基因，17个属和7个物种的生物标记物的丰富性显示了对HPV16阳性个体的极好的预测能力，其接收者工作特征曲线（AUC）下的面积分别为0.861、0.819和0.918。我们进一步表征了微生物的功能，并揭示了HPV16阳性的女性富含新陈代谢和膜运输，并且由于聚糖的生物合成和代谢以及复制和修复而枯竭。定量PCR测量验证了HPV16阳性女性中一种基因标记和三种物种显着富集。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组的组成和功能发生了变化，