Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
Int J Cancer. 2012 Aug 15;131(4):E579-85. doi: 10.1002/ijc.26496. Epub 2011 Nov 17.
High-grade cervical intraepithelial neoplasia (CIN2/3) represents a heterogeneous disease both with respect to clinical behavior and chromosomal aberrations detected. We hypothesized that the extent of chromosomal aberrations reflects the duration of their existence. Chromosomal profiles were determined of CIN3 of women with a known 5-year history of high-risk human papillomavirus virus (hrHPV) infection, in which duration of prior hrHPV infection was considered a proxy for duration of CIN3 existence. Eleven women had a <5 year preceding hrHPV infection (CIN3<5yrPHI) and 24 had a PHI lasting ≥5 years (CIN3≥5yrPHI). For comparison, six CIN3 adjacent to squamous cell carcinomas (CIN3-SCC), the corresponding SCCs, and six CIN1 were included. Unsupervised hierarchical clustering analysis of the chromosomal profiles revealed two clusters. One was characterized by a low number of chromosomal aberrations and included all CIN1, 81.8% of CIN3<5yrPHI and 33.3% of CIN3≥5yrPHI. Samples in the second cluster, displaying multiple aberrations, included 18.2% of CIN3<5yrPHI, 66.7% CIN3≥5yrPHI, all except one CIN3-SCC and all SCCs. The number of genomic aberrations increased according to lesion grade and also with longer duration of PHI. The increase in aberrations in CIN3≥5yrPHI compared to <5yrPHI was highly significant (p = 0.001), suggesting that CIN3≥5yrPHI represent more severe lesions. In conclusion, longer duration of preceding hrHPV infection is associated with an increased number of chromosomal aberrations. Hence, CIN3 with a longer duration of existence are likely more prone to have an increased short-term risk of cervical cancer.
高级别宫颈上皮内瘤变（CIN2/3）在临床行为和染色体异常方面均表现出异质性。我们假设染色体异常的程度反映了它们存在的时间。我们对有明确 5 年高危型人乳头瘤病毒（hrHPV）感染史的 CIN3 女性的染色体图谱进行了测定，其中，hrHPV 感染的持续时间被认为是 CIN3 存在时间的替代指标。11 名女性的 hrHPV 感染时间<5 年（CIN3<5yrPHI），24 名女性的 PHI 持续时间≥5 年（CIN3≥5yrPHI）。为了比较，还纳入了 6 例 CIN3 紧邻鳞状细胞癌（CIN3-SCC）、相应的 SCC 和 6 例 CIN1。对染色体图谱的无监督层次聚类分析显示出两个聚类。一个聚类的特点是染色体异常数量较少，包括所有 CIN1、81.8%的 CIN3<5yrPHI 和 33.3%的 CIN3≥5yrPHI。另一个聚类显示出多个异常的样本，包括 18.2%的 CIN3<5yrPHI、66.7%的 CIN3≥5yrPHI、除一个 CIN3-SCC 外的所有 CIN3-SCC 和所有 SCC。根据病变程度和 PHI 持续时间的长短，基因组异常数量增加。与<5yrPHI 相比，CIN3≥5yrPHI 中的异常增加非常显著（p = 0.001），这表明 CIN3≥5yrPHI 代表更严重的病变。总之，更长时间的先前 hrHPV 感染与更多的染色体异常有关。因此，存在时间较长的 CIN3 更有可能在短期内增加宫颈癌的风险。
