文章：

（epi）基因改变在hpv诱导的宫颈癌前病变中的临床意义

Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions

原文发布日期：2014-05-23

DOI: 10.1038/nrc3728

类型: Review Article

开放获取: 否

要点：

1. Cervical intraepithelial neoplasia (CIN) lesions can be divided into productive (CIN1 and CIN2) and transforming (CIN2 and CIN3) lesions. Morphologically, productive CIN2 cannot be distinguished from transforming CIN2.
2. Transforming CIN reflects a heterogeneous disease. Early and advanced transforming CIN lesions, displaying a low and high short-term progression risk for cancer, respectively, can be distinguished on the basis of molecular host cell alterations.
3. When applied to cervical scrapings, specific methylation markers, such as cell adhesion molecule 1 (CADM1), myelin and lymphocyte (MAL) and mir-124-2, detect advanced transforming CIN and cancer with a high sensitivity.
4. CIN2/CIN3 lesions detected by specific methylation markers are in need of immediate treatment, given their high short-term progression risk for cancer.
5. Cytology detects morphological cellular abnormalities associated with CIN2, CIN3 and cancer with a moderate sensitivity, but may miss cancer and advanced transforming CIN with a high short-term progression risk for cancer.
6. Human papilloma virus (HPV) testing will replace cytology as the primary screening tool for cervical cancer.
7. Clinically validated panels of methylation markers, such as CADM1, MAL and mir-124-2, can be used as triage markers for HPV-positive women. Methylation marker panels with a high sensitivity for cancer have the potential to function as a primary screening tool.
8. DNA methylation marker panels may also be used for the management of women with CIN lesions to prevent overtreatment of CIN2/CIN3 lesions.
9. The compatibility of methylation markers with HPV testing and self-sampling has the potential for full molecular cervical screening in the near future.

要点翻译：

1. 宫颈上皮内瘤变（CIN）可分为增殖性病变（CIN1和CIN2）与转化性病变（CIN2和CIN3）。在形态学上，增殖性CIN2与转化性CIN2无法区分。
2. 转化性CIN反映的是一种异质性疾病。根据分子宿主细胞改变，可区分早期和晚期转化性CIN病变，二者分别表现为短期进展为癌症的低风险和高风险。
3. 当应用于宫颈刮片时，特定甲基化标志物（如细胞粘附分子1（CADM1）、髓鞘和淋巴细胞（MAL）以及mir-124-2）能以高灵敏度检测晚期转化性CIN和癌症。
4. 经特定甲基化标志物检测出的CIN2/CIN3病变需立即治疗，因其短期进展为癌症的风险较高。
5. 细胞学检测以中等灵敏度识别与CIN2、CIN3及癌症相关的形态学细胞异常，但可能漏检具有高短期癌症进展风险的癌症和晚期转化性CIN。
6. 人乳头瘤病毒（HPV）检测将取代细胞学作为宫颈癌的主要筛查工具。
7. 经过临床验证的甲基化标志物组合（如CADM1、MAL和mir-124-2）可作为HPV阳性女性的分流标志物。对癌症具有高灵敏度的甲基化标志物组合有潜力成为主要筛查工具。
8. DNA甲基化标志物组合也可用于管理CIN病变女性，以防止对CIN2/CIN3病变的过度治疗。
9. 甲基化标志物与HPV检测及自我采样的兼容性，有望在不久的将来实现全分子宫颈筛查。

英文摘要：

Infection of cervical epithelium with high-risk human papilloma virus (hrHPV) might result in productive or transforming cervical intraepithelial neoplasia (CIN) lesions, the morphology of which can overlap. In transforming CIN lesions, aberrations in host cell genes accumulate over time, which is necessary for the ultimate progression to cancer. On the basis of (epi)genetic changes, early and advanced transforming CIN lesions can be distinguished. This paves the way for new molecular tools for cervical screening, diagnosis and management of cervical cancer precursor lesions.

摘要翻译： 

宫颈上皮感染高危型人乳头瘤病毒（hrHPV）可能导致增殖性或转化性宫颈上皮内瘤变（CIN）病变，两者的形态可能重叠。在转化性CIN病变中，宿主细胞基因异常会随时间累积，这是最终进展为癌症所必需的。基于（表观）遗传变化，可以区分早期和晚期转化性CIN病变。这为开发用于宫颈癌筛查、诊断和管理宫颈癌前病变的新型分子工具铺平了道路。

原文链接：

Clinical implications of (epi)genetic changes in HPV-induced cervical precancerous lesions