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[人乳头瘤病毒:起源、致癌因素及宫颈癌筛查标志物]

[Human papillomaviruses : origin, oncogenic factors and markers for cervical cancer screening].

作者信息

Grange Aurélie, Mouton Victor, Roojee Mael, Rosec Sylvain, Tran Adissa, Payan Christopher

出版信息

Virologie (Montrouge). 2024 Dec 30;28(6):357-368. doi: 10.1684/vir.2024.1069.

Abstract

The Human papillomaviruses (HPV) have existed in the human population since the archaic hominids. Over the course of human migration and evolution, HPVs have co-evolved with humans on all continents to become today the leading cause of cervical cancer. HPVs are classified by genera, species, genotype, lineage, sub-lineage and variants. Among more than 200 HPV genotypes, HPV16 is the most common and the most oncogenic at high-risk (HPV-HR). If viral oncogenesis is governed by numerous factors and mechanisms involving the virus and its host, the E6/E7 oncogenic proteins of HR-HPV play a central role and are always expressed in cervical cancers. Those of HPV16 have the greatest affinity for cellular proteins involved in cellular control, p53/E6 and pRb/E7. Some E6/E7 HPV16 mutants are associated with persistent infection, correlating with viral lineages and their ethnic and geographical origin. If the splicing of viral mRNAs encoding E6/E7 allows the overexpression of the E7 protein, which is an essential condition for the establishment of HR-HPV oncogenesis, other mechanisms contribute to strengthening it. On the one hand, the accidental integration of the viral genome, in particular the E1/E2 coding region, participates in the transformation of the infected cell. On the other hand, hypermethylation of the viral L1/L2 genomic regions is observed in the advanced stages of infection. Different methods for analyzing mutations, splice sites, integrations and methylations of the viral genome have been described. These virological markers could complete the detection of HR-HPV in the context of cervical cancer screening, currently recommended in France.

摘要

自古代原始人类以来,人乳头瘤病毒(HPV)就已存在于人类群体中。在人类迁徙和进化过程中,HPV在各大洲与人类共同进化,如今已成为宫颈癌的主要病因。HPV按属、种、基因型、谱系、亚谱系和变体进行分类。在200多种HPV基因型中,HPV16最为常见,也是高危型(HPV-HR)中最具致癌性的。如果病毒致癌作用受涉及病毒及其宿主的众多因素和机制支配,那么高危型HPV的E6/E7致癌蛋白起着核心作用,且在宫颈癌中总是表达。HPV16的E6/E7蛋白对参与细胞调控的细胞蛋白p53/E6和pRb/E7具有最大亲和力。一些HPV16 E6/E7突变体与持续感染有关,这与病毒谱系及其种族和地理起源相关。如果编码E6/E7的病毒mRNA的剪接允许E7蛋白过度表达,这是高危型HPV致癌作用确立的必要条件,那么其他机制也有助于强化这一过程。一方面,病毒基因组的意外整合,特别是E1/E2编码区,参与了受感染细胞的转化。另一方面,在感染后期观察到病毒L1/L2基因组区域的高甲基化。已经描述了分析病毒基因组突变、剪接位点、整合和甲基化的不同方法。这些病毒学标志物可以在法国目前推荐的宫颈癌筛查背景下完善高危型HPV的检测。

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