Osei Sekyere John, Trama Jason, Adelson Martin, Trikannad Charulata, DiBlasi Desiree, Schuster Rachel, Yang Jing Jing, Mordechai Eli
Institute of Biomarker Research, Department of Clinical Development, Medical Diagnostic Laboratories, Hamilton Township, NJ 08690, USA.
Department of Medical Microbiology, School of Medicine, University of Pretoria, Pretoria 0084, South Africa.
iScience. 2025 Sep 2;28(10):113473. doi: 10.1016/j.isci.2025.113473. eCollection 2025 Oct 17.
The cervicovaginal microbiome modulates susceptibility to bacterial vaginosis (BV), high-risk human papillomavirus (hrHPV) infection, and epithelial cell abnormalities that precede cervical cancer. We retrospectively analyzed 15 607 qPCR-profiled cervicovaginal specimens from U.S. women (ages 14-95; 32 states) and integrated microbiome abundances, hrHPV genotyping, Pap-cytology, and demographics. BV was present in 53% and hrHPV in 11% of samples. Lactobacillus crispatus, L. gasseri, and L. jensenii were enriched in BV-negative and cytologically normal (NILM) samples, whereas L. iners and BV-associated anaerobes co-occurred with hrHPV and abnormal cytology. Machine-learning models confirmed age, hrHPV status, and L. crispatus abundance as the strongest multivariate predictors of BV and cytological outcomes (BV AUROC ≈0.97). Interaction analyses revealed synergistic associations between specific hrHPV genotypes and Gardnerella/Fannyhessea that further increased cytological risk. These findings underscore the clinical value of microbiome profiling and support probiotic strategies that promote protective Lactobacillus communities to reduce BV and hrHPV-related cervical pathology.
宫颈阴道微生物群调节细菌性阴道病（BV）、高危型人乳头瘤病毒（hrHPV）感染以及宫颈癌前上皮细胞异常的易感性。我们回顾性分析了来自美国女性（年龄14 - 95岁；32个州）的15607份经qPCR分析的宫颈阴道样本，并整合了微生物群丰度、hrHPV基因分型、巴氏细胞学检查结果和人口统计学数据。53%的样本存在BV，11%的样本存在hrHPV。卷曲乳杆菌、加氏乳杆菌和詹氏乳杆菌在BV阴性且细胞学检查正常（未见上皮内病变或恶性病变，NILM）的样本中富集，而惰性乳杆菌和与BV相关的厌氧菌则与hrHPV及细胞学异常同时出现。机器学习模型证实年龄、hrHPV状态和卷曲乳杆菌丰度是BV和细胞学检查结果最强的多变量预测因素（BV的受试者工作特征曲线下面积约为0.97）。交互分析揭示了特定hrHPV基因型与加德纳菌属/芬尼希菌属之间的协同关联，进一步增加了细胞学风险。这些发现强调了微生物群分析的临床价值，并支持采用益生菌策略来促进具有保护作用的乳杆菌群落，以降低BV和hrHPV相关的宫颈病变。
