Cervicovaginal microbiome, high-risk HPV infection and cervical cancer: Mechanisms and therapeutic potential

IF 6.1 1区 生物学 Q1 MICROBIOLOGY
Roujie Huang , Zimo Liu , Tianshu Sun , Lan Zhu
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Abstract

The microbiota in the female genital tract is an intricate assembly of diverse aerobic, anaerobic, and microaerophilic microorganisms, which share the space within the reproductive tract and engage in complex interactions. Microbiome dysbiosis may disrupt the symbiotic relationship between the host and microorganisms and play a pivotal role in the pathogenesis of various diseases, including its involvement in the establishment of human papillomavirus (HPV)-associated cervical cancer (CC). Interventions to restore microbiota homeostasis (e.g., probiotics) and bacterial-vector HPV therapeutic vaccines have been reported to be potentially effective in clearing HPV infection and ameliorating cytological abnormalities. In this review, we place emphasis on elucidating the alterations within the cervical–vaginal microbiota as well as the intratumoral microbiota in the context of high-risk HPV (HR-HPV) infection and its subsequent progression to cervical intraepithelial neoplasia/CC. Furthermore, we explore the mechanisms by which these microbial communities exert potential pathogenic or protective effects, including modulating genital inflammation and immune responses, affecting HR-HPV oncogene expression and oncoprotein production, regulating oxidative stress and deoxyribonucleic acid (DNA) damage, and inducing metabolic rewiring. Lastly, we summarize the latest evidence in human trials regarding the efficacy of probiotics, prebiotics and probiotic-vector HPV therapeutic vaccines. This review aims to foster a deeper understanding of the role of the microbiota in HR-HPV infection-related cervix cancer development, and further provide a theoretical basis for the development of preventive and therapeutic strategies based on microbial modulation.

宫颈阴道微生物组、高危 HPV 感染与宫颈癌:机制与治疗潜力
女性生殖道中的微生物群是由多种需氧、厌氧和微嗜氧微生物组成的复杂集合体,它们共享生殖道内的空间并进行复杂的相互作用。微生物群失调可能会破坏宿主与微生物之间的共生关系,并在各种疾病的发病机制中发挥关键作用,包括参与人乳头状瘤病毒(HPV)相关宫颈癌(CC)的形成。据报道,恢复微生物群平衡的干预措施(如益生菌)和细菌载体 HPV 治疗疫苗可能会有效清除 HPV 感染并改善细胞学异常。在这篇综述中,我们将重点阐明在高危型 HPV(HR-HPV)感染及其随后发展为宫颈上皮内瘤变/CC 的过程中,宫颈阴道微生物群和瘤体内微生物群的改变。此外,我们还探讨了这些微生物群落发挥潜在致病或保护作用的机制,包括调节生殖器炎症和免疫反应、影响 HR-HPV 肿瘤基因的表达和肿瘤蛋白的产生、调节氧化应激和脱氧核糖核酸(DNA)损伤以及诱导代谢重构。最后,我们总结了益生菌、益生元和益生菌载体人乳头瘤病毒治疗疫苗疗效的最新人体试验证据。本综述旨在加深人们对微生物群在与HR-HPV感染相关的宫颈癌发展中的作用的理解,并进一步为开发基于微生物调节的预防和治疗策略提供理论依据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Microbiological research
Microbiological research 生物-微生物学
CiteScore
10.90
自引率
6.00%
发文量
249
审稿时长
29 days
期刊介绍: Microbiological Research is devoted to publishing reports on prokaryotic and eukaryotic microorganisms such as yeasts, fungi, bacteria, archaea, and protozoa. Research on interactions between pathogenic microorganisms and their environment or hosts are also covered.
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