Rashwan Hannah H, Ali Mohammed H, Mostafa Mazen M, Ramadan Raghda, Mysara Mohamed
Bioinformatics Group, Centre for Informatics Science (CIS), School of Information Technology and Computer Science (ITCS), Nile University, Giza, 12677, Egypt.
School of Biotechnology, Nile University, Giza, 12677, Egypt.
Hum Genomics. 2025 Aug 12;19(1):89. doi: 10.1186/s40246-025-00795-w.
Cervical cancer (CC) is the fourth most prevalent malignancy among women worldwide, where 99.7% of the cases are linked to persistent human papillomavirus (HPV) infections. While emerging evidence suggests a role for vaginal microbiome dysbiosis in HPV-driven CC, the specific microbial alterations and their functional implications remain unclear. However, inconsistencies in identifying specific microbial signatures-largely due to heterogeneous study designs, targeted 16S rRNA regions, and data processing methods-have limited the generalizability of existing findings. To address these challenges, we conducted a standardized mega-analysis using a compositionality-aware approach to ensure consistency and minimize technical bias across studies.
Our mega-analysis consolidates findings from five case-control 16S rRNA ampilicon sequencing studies, encompassing 215 samples. Compared to healthy controls, CC patients exhibited significantly higher alpha diversity (Shannon index, p <0.005) and a shift from a Lactobacillus-dominant to a polymicrobial vaginal microbiome. This microbial dysbiosis was characterized by an increased abundance of Porphyromonadaceae, particularly Porphyromonas asaccharolytica, and other anaerobic bacterial species such as Campylobacter ureolyticus, Peptococcus niger, and Anaerococcus obesiensis (FDR <0.05). Functional profiling of the altered microbiome revealed enrichment in pathways associated with chronic inflammation, fatty acid biosynthesis, amino acid metabolism, cellular proliferation, invasion, and metastasis.
This mega-analysis presents the most methodologically homogeneous study to date of CC-associated vaginal microbiome using publicly available 16S datasets. Our findings not only deepen our understanding of microbial influences on CC but also pave the way for novel diagnostic and therapeutic approaches potentially enhancing patient outcomes in CC care. These insights open new avenues for clinical interventions that extend beyond conventional HPV-centric strategies.
宫颈癌（CC）是全球女性中第四大常见恶性肿瘤，其中99.7%的病例与持续性人乳头瘤病毒（HPV）感染有关。虽然新出现的证据表明阴道微生物群失调在HPV驱动的宫颈癌中起作用，但具体的微生物改变及其功能影响仍不清楚。然而，在识别特定微生物特征方面存在不一致性——主要是由于研究设计、靶向16S rRNA区域和数据处理方法的异质性——限制了现有研究结果的普遍性。为了应对这些挑战，我们采用了一种考虑组成性的方法进行标准化的荟萃分析，以确保研究之间的一致性并最大限度地减少技术偏差。
我们的荟萃分析整合了五项病例对照16S rRNA扩增子测序研究的结果，涵盖215个样本。与健康对照相比，宫颈癌患者表现出显著更高的α多样性（香农指数，p<0.005），并且阴道微生物群从以乳酸杆菌为主转变为多种微生物群落。这种微生物失调的特征是卟啉单胞菌科，特别是解糖卟啉单胞菌，以及其他厌氧细菌种类如解脲弯曲菌、黑色消化球菌和肥胖厌氧球菌的丰度增加（FDR<0.05）。对改变的微生物群进行功能分析发现，与慢性炎症、脂肪酸生物合成、氨基酸代谢、细胞增殖、侵袭和转移相关的途径富集。
这项荟萃分析是迄今为止使用公开可用的16S数据集对与宫颈癌相关的阴道微生物群进行的方法学上最一致的研究。我们的研究结果不仅加深了我们对微生物对宫颈癌影响的理解，也为可能改善宫颈癌护理患者结局的新诊断和治疗方法铺平了道路。这些见解为超越传统以HPV为中心策略的临床干预开辟了新途径。
