Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique
Integrated human papillomavirus type 16 is frequently found in cervical cancer precursors as demonstrated by a novel quantitative real-time PCR technique
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DOI：
10.1128/jcm.40.3.886-891.2002
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发表时间：
2002-03-01
影响因子：
9.4
通讯作者：
Syrjänen, S
中科院分区：
文献类型：
--
作者：
Peitsaro, P;Johansson, B;Syrjänen, S
与宫颈癌不同，人乳头瘤病毒（HPV）DNA整合到宿主基因组中被认为是癌症前体病变（宫颈上皮内瘤变\CIN\）中的罕见事件。通过我们新的实时PCR方法，我们证明了整合的HPV 16型（HPV16）已经存在于CIN病变中。同时检测HPV16的物理状态和病毒载量。在HPV 16整合期间最常缺失的E2开放阅读框（ORF）的独特区域被一组PCR引物和探针靶向，另一组靶向E6 ORF。在附加型形式中，两个靶标应该是等同的，而在整合型形式中，E2的拷贝数将小于E6的拷贝数。该方法进行了测试与DNA从31宫颈病变（非CIN CINIII）从24名妇女前瞻性随访10年。本报告介绍了迄今为止描述的最大系列或CIN病变的病毒载量和整合结果。只有一个样本含有唯一的附加型HPV 16 DNA，这种病变消退自发。来自另一名患者的样本，仅整合了HPV16，在2年内从CINI迅速进展为CINIII。在所有其他患者中，发现游离型和整合型HPV 16 DNA共存。CIN病变的快速进展与整合的HPV16的高负荷密切相关。因此，这里描述的方法是一种非常敏感的工具，可以用来评估HPV的物理状态，这在预测疾病进展方面是有用的。
In contrast to cervical cancer, integration of human papillomavirus (HPV) DNA into the host genome has been considered a rare event in cancer precursor lesions (cervical intraepithelial neoplasia \CIN\). With our new real-time PCR method, we demonstrated that integrated HPV type 16 (HPV16) is already present in CIN lesions. The physical state of HPV16 and the viral load were simultaneously detected. A unique region of the E2 open reading frame (ORF) that is most often deleted during HPV16 integration is targeted by one set of PCR primers and a probe, and another set targets the E6 ORF. In episomal form, both targets should be equivalent, while in integrated form, the copy numbers of E2 would be less than those of E6. The method was tested with DNAs from 31 cervical lesions (non-CIN to CINIII) from 24 women prospectively followed up for 10 years. This report presents viral load and integration results from the largest series or CIN lesions described to date. Only one sample contained exclusively episomal HPV16 DNA, and this lesion regressed spontaneously. Samples from another patient, with only integrated HPV16, rapidly progressed from CINI to CINIII in 2 years. In all other patients, episomal and integrated forms of HPV16 DNA were found to coexist. Rapid progression of the CIN lesions was closely associated with a heavy load of integrated HPV16. Thus, the method described here is a very sensitive tool with which to assess the physical state of HPV, which is useful in predicting disease progression.