Zhang Wei, Ge Yan, Yao Lihe, Yan Qingchun, Wei Jiuju, Yin Yanfei, Liu Bin
The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.
The School of Stomatology, Lanzhou University, Lanzhou, China.
Cancer Rep (Hoboken). 2025 Jun;8(6):e70246. doi: 10.1002/cnr2.70246.
We aimed to conduct a systematic review and meta-analysis of high-throughput sequencing studies to assess changes in microbiome alpha, beta diversity, and composition differences in patients with human papillomavirus (HPV) infection and cervical cancer.
The PubMed, Embase, Web of Science, and Cochrane Library databases were systematically searched to include original studies. The effect size estimates with a 95% confidence interval were combined using a random effects model. The meta-analysis was performed using the Stata MP16 software.
A total of 64 studies were included, with a meta-analysis of the diversity index performed on a subset of seven studies. Microbial diversity of patients infected with HPV was observed to be significantly different from that of healthy controls (CHAO index: 95% CI 0.42, 5.03, I = 99.18%, p < 0.05). Subgroup analysis based on the sample collection region showed a significant difference between vaginal microbiota of the treatment group and control group, as measured by the Shannon index (95% CI 0.12, 0.97, I = 67.09%, p < 0.05). Further, subgroup analysis of samples sequenced with the primer pair for the V3-V4 region showed a statistically significant difference in alpha diversity (Shannon index: 95% CI 0.28, 0.72, I = 0.00%, p < 0.05) between treatment and control groups. The microbial diversity varied between patients with inferior cervical lesions (low-grade squamous intraepithelial lesion) and healthy controls (Shannon index: 95% CI 0.02, 0.58, I = 0.00%, p < 0.05). The bacterial marker genera differed at each cervical lesion stage. Gardnerella was prevalent during the HPV infection stage, but its proportion decreased after the occurrence of cervical lesions. In contrast, the proportions of Prevotella, Porphyromonas, and Dialister increased during the cervical cancer stages.
Patients with simple HPV infections frequently exhibit unstable microbial diversity and are influenced by various factors. The microbial environment continues to change after the occurrence of cervical lesions and is correlated with the severity of cervical lesions.
我们旨在对高通量测序研究进行系统评价和荟萃分析，以评估人乳头瘤病毒（HPV）感染和宫颈癌患者微生物组的α多样性、β多样性及组成差异的变化。
系统检索PubMed、Embase、Web of Science和Cochrane图书馆数据库以纳入原始研究。采用随机效应模型合并95%置信区间的效应量估计值。使用Stata MP16软件进行荟萃分析。
共纳入64项研究，对其中7项研究的子集进行了多样性指数的荟萃分析。观察到HPV感染患者的微生物多样性与健康对照者显著不同（CHAO指数：95%置信区间0.42，5.03，I=99.18%，p<0.05）。基于样本采集区域的亚组分析显示，治疗组和对照组的阴道微生物群存在显著差异，以香农指数衡量（95%置信区间0.12，0.97，I=67.09%，p<0.05）。此外，对用V3-V4区域引物对测序的样本进行亚组分析显示，治疗组和对照组之间的α多样性存在统计学显著差异（香农指数：95%置信区间0.28，0.72，I=0.00%，p<0.05）。宫颈低度病变（低级别鳞状上皮内病变）患者与健康对照者的微生物多样性有所不同（香农指数：95%置信区间0.02，0.58，I=0.00%，p<0.05）。在每个宫颈病变阶段，细菌标记属均有所不同。加德纳菌在HPV感染阶段普遍存在，但在宫颈病变发生后其比例下降。相反，普雷沃菌属、卟啉单胞菌属和戴阿利斯特菌属在宫颈癌阶段的比例增加。
单纯HPV感染患者经常表现出不稳定的微生物多样性，并受多种因素影响。宫颈病变发生后，微生物环境持续变化，且与宫颈病变的严重程度相关。
