人端粒酶RNA基因扩增和高危型HPV感染检测对宫颈癌及宫颈上皮内瘤变的预测意义

Prediction of Cervical Cancer and Cervical Intraepithelial Neoplasia by Amplification of Human Telomerase RNA Gene(hTERC) and Detection of High-risk Human Papillomavirus Infection

目的:研究人端粒酶RNA基因(hTERC)扩增及高危型人乳头瘤病毒(HR-HPV)在宫颈癌和宫颈上皮内瘤变(CIN)脱落细胞的表达,以探讨其在早期宫颈病变和疾病发展的作用和临床意义。方法:分别采用荧光原位杂交技术(FISH)和第2代杂交捕获法(HCⅡ),检测26例宫颈良性病变/湿疣、27例CIN、41例浸润性宫颈癌(ICC)共94例患者的hTERC基因扩增杂交信号数及HR-HPV阳性感染,上述两种检测方法与宫颈病理组织学结果对照。结果:hTERC基因在ICC组阳性表达为85.37%,高于CINⅡ～Ⅲ组(15.83%)、CINⅠ组(7.14%)与良性病变组(6.67%,1/15),差异有高度统计学意义(P<0.01);HR-HPV阳性感染率在良性病变/湿疣、CINⅠ、CINⅡ～Ⅲ、ICC分别为46.15%,71.43%,38.46%和19.51%;hTERC基因FISH检测对宫颈上皮病变的阳性预测值(PPV)和特异度(Sp)分别为92.68%、88.46%,明显高于HR-HPV-HCⅡ检测(65.71%、53.85%),P<0.01;敏感度(Se)55.88%,阴性预测值(NPV)43.40%,亦高于后者(33.82%、23.73%),P<0.05。结论:hTERC基因FISH检测与HR-HPV-HCⅡ检测比较能更可靠地辨别宫颈病变的程度;检测hTERC基因扩增对判断早期宫颈病变进展风险可能有一定的预测意义,有望作为宫颈癌早期筛查、病情判断和评估预后的辅助指标之一。

Objective：To explore the amplification of Human Telomerase RNA gene（ hTERC） and the expression of high-risk Human Papilomavirus （HR-HPV） in cervical shed cells from invasive cervical cancer（ICC） and cervical intraepithelial neoplasia（CIN）,and to evaluate their effect and clinical significance in the early stage of cervical lesion and development of disease. Methods：Fluorescence in situ hybridization （FISH） and hybrid captureⅡ（HCⅡ） were used to detect the expression of hTERC gene and HR-HPV infection in 41 cases of ICC,27 cases of CIN and 26 cases of benign cervical lesion/condyloma,meanwhile,the results of these two methods were compared with the results of cervical histopathology. Results：There was significant difference in positive expression rate of hTERC gene in ICC （85.37%） compared with CINⅡ-Ⅲ （15.83%）,CINⅠ（7.14%） and benign cervical lesion（6.67%） （P〈0.01）. Positive infection rate of HR-HPV in benign cervical lesion/ condyloma,CINⅠ,CINⅡ-Ⅲ and ICC was 46.15%,71.43%,38.46% and 19.51% respectively. The positive predictive value（ PPV） and specificities（ Sp） of hTERC gene in cervical epithelial lesions by FISH was 92.68% and 88.46%,which was significantly higher than that by HR-HPV HCⅡ test （65.71% and 53.85%,P0.01）. The Sensitivity （ Se ） and negative predictive value（NPV） of hTERC gene in cervical epithelial lesion by FISH was 55.88% and 43.40%,which was higher than that by HR-HPV HCⅡ test （Se 33.82%,,NPV 23.73%,P0.05）.Conclusions：Detection of hTERC gene by FISH is more reliable to different the degree of cervical lesion than HR-HPV HCII. Detection of hTERC gene amplification may has some predictive significance in the judgment of the progressive risk of early cervical lesion,which may be used as a forecast index for early screening of cervical cancer,judging disease severity and evaluating prognosis.