The significance of human papillomavirus integration in carcinogenesis and the development of specific diagnostics and countermeasures

Jiaxu Ying, Gary Wong, N. Berthet
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Abstract

Human papillomavirus (HPV) infection is associated with various tumors, notably in the cervix, oropharyngeal region, and anus. As the disease progresses, integration of the viral genome into the host genome is often observed, yet the means of integration and its intrinsic relationship to carcinogenesis remain unclear. To address this gap, novel sequencing technologies have been developed to enhance the accuracy, intuitiveness, and cost-effectiveness of identifying integration breakpoints. HPV genome integration is thought to induce imbalances or dysfunctions in gene expression, epigenetic changes, chromosomal translocation, and genetic instability. The precise mechanisms underlying the changes in gene expression caused by genome integration offer avenues for tumor risk prediction and prognosis assessment. Personalized precision medicine, grounded in the integration patterns unique to each patient, holds promise for cancer treatment. This review summarizes and discusses the current state of knowledge regarding the mechanisms, carcinogenesis, detection and analysis, and clinical significance of HPV integration. It synthesizes existing information to offer a comprehensive overview, potentially enhancing our understanding of HPV-related tumorigenesis and aiding in the development of more effective diagnostic and therapeutic strategies.
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人类乳头状瘤病毒整合在致癌过程中的意义以及特异性诊断和对策的开发
人类乳头瘤病毒(HPV)感染与多种肿瘤有关,尤其是子宫颈、口咽区和肛门。随着病情的发展,经常可以观察到病毒基因组与宿主基因组的整合,但整合的方式及其与癌变的内在关系仍不清楚。为了弥补这一缺陷,人们开发了新型测序技术,以提高识别整合断点的准确性、直观性和成本效益。据认为,HPV 基因组整合会诱发基因表达失衡或功能障碍、表观遗传学变化、染色体易位和遗传不稳定性。基因组整合引起基因表达变化的精确机制为肿瘤风险预测和预后评估提供了途径。以每个患者特有的整合模式为基础的个性化精准医疗为癌症治疗带来了希望。本综述总结并讨论了目前有关 HPV 整合的机制、致癌、检测和分析以及临床意义的知识现状。它综合了现有信息,提供了一个全面的概述,有可能加深我们对 HPV 相关肿瘤发生的了解,并有助于开发更有效的诊断和治疗策略。
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