背景:本研究的目的是评估人乳头瘤病毒(HPV)和宫颈癌(CC)患者阴道和口腔环境中的微生物变异和生物标志物,并开发新的预测模型。
方法:本研究包括从82名妇女的阴道和口腔龈下菌斑收集的164个样本。参与者根据其阴道和口腔样本分为四个不同的组:对照组(Z/KZ,n=22),流产组(AB/KAB,n=17),HPV感染组(HP/KHP,n=21),和宫颈癌组(CC/KCC,n=22)。使用PacBio平台的全长16SrDNA基因测序进行微生物区系分析。
结果:Z和AB组的阴道细菌群落表现出相对简单的结构,主要由乳杆菌主导。然而,CC组显示出较高的厌氧菌丰度和α多样性。生物标志物,如拟杆菌,支原体,芽孢杆菌,Dialister,卟啉单胞菌,缺氧球菌,和Prevotella被确定为CC的指标。血液C反应蛋白(CRP)水平升高与局部/全身炎症之间建立了相关性,怀孕,分娩,堕胎,这导致了阴道微环境的不均匀性。氨基酸代谢证实了CC组中微生物多样性的改变。口腔微生物多样性表现出与阴道微生物组相反的模式,表明一种独特的关系。KCC组的微生物多样性显著低于KZ组,表明口腔健康和癌症发展之间的联系。几种微生物,包括梭杆菌,弯曲杆菌,Capnocytophaga,Veillonella,链球菌,Lachnoanaerobactrum,丙酸杆菌,普雷沃氏菌,乳酸菌,还有奈瑟氏菌,被鉴定为CC生物标志物。此外,牙周病原菌与血CRP水平和口腔卫生状况相关。CC组口腔微生物氨基酸代谢升高与病原体的存在密切相关。正相关表明阴道和口腔细菌之间存在协同关系。
结论:HPV感染和CC影响阴道和口腔微环境,影响全身代谢和细菌之间的协同作用。这表明使用口腔菌群标记是诊断CC的潜在筛选工具。
BACKGROUND: The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models.
METHODS: This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform.
RESULTS: The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria.
CONCLUSIONS: HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC.