Wilting Saskia M, Steenbergen Renske D M
Department of Pathology, VU University Medical Center Amsterdam, The Netherlands.
Department of Pathology, VU University Medical Center Amsterdam, The Netherlands.
Papillomavirus Res. 2016 Dec;2:85-88. doi: 10.1016/j.pvr.2016.04.003. Epub 2016 Apr 12.
Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV) and develops via precursor stages, called cervical intraepithelial neoplasia (CIN). High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1) increase our understanding of cervical carcinogenesis, 2) yield biomarkers for early diagnosis, and 3) identify therapeutic targets for HPV-induced (pre) cancerous lesions. This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.
宫颈癌由高危型人乳头瘤病毒（hrHPV）引发，并通过称为宫颈上皮内瘤变（CIN）的前驱阶段发展而来。当病毒癌基因E6和E7在分裂细胞中异常表达时，高级别CIN病变被认为是真正的癌前病变。这会通过p53和pRb降解导致正常细胞周期控制被破坏。然而，已经明确这些病毒癌基因具有额外的致癌特性，包括干扰DNA甲基化机制和有丝分裂检查点。识别导致高级别瘤变的分子事件将：1）增进我们对宫颈癌发生机制的理解；2）产生早期诊断的生物标志物；3）识别HPV诱导的（癌前）病变的治疗靶点。本综述将简要总结我们目前对HPV诱导的致癌过程中宿主细胞基因组分子改变的理解进展。
