人乳头瘤病毒载量和人端粒酶RNA组分基因与子宫颈病变的关系

目的研究子宫颈脱落细胞中人乳头瘤病毒（HPV）载量和人端粒酶RNA组分（hTERC）基因的表达与子宫颈上皮内瘤样病变（CIN）之间的关系。方法北京大学深圳医院子宫颈癌早诊早治中心诊断CINⅠ、CINⅡ/Ⅲ及浸润癌的患者分别为105例、59例、10例,并以51例非CIN（病理正常或炎症）者为对照。所有研究对象均取宫颈脱落细胞行HC-Ⅱ法高危型HPV（HR-HPV）和检测荧光原位杂交（FISH）法hTERC基因检测。结果 （1）根据组织学结果分为非CIN、CINⅠ、CINⅡ/Ⅲ和浸润癌组,各组HPV的阳性率分别为58.82%、67.62%、98.31%和100.00%,组间差异有统计学意义（P〈0.01）;非CIN、CINⅠ、CINⅡ/Ⅲ和浸润癌组病毒载量均值分别为135.67、345.04、535.08和612.62,CINⅡ/Ⅲ和浸润癌组的HPV病毒载量均值高于非CIN组（P〈0.05）。随着病变程度加重,HPV阳性率和病毒载量均增加。（2）非CIN、CINⅠ、CINⅡ/Ⅲ和浸润癌组hTERC扩增率分别为3.92%、5.71%、57.63%和90.00%,各组间hTERC差异存在统计学意义（P〈0.01）;在CINⅡ/Ⅲ及浸润癌组hTERC扩增率显著增高,为非CIN和CINⅠ的10～15倍。各组hTERC扩增均数分别为6.50、9.00、17.81、36.50,扩增均数随病变加重明显升高,CINⅠ与非CIN组之间差异无统计学意义（P〉0.05）,其余各组间差异均有统计学意义（P〈0.01）。CINⅡ/Ⅲ及浸润癌组hTERC扩增均数为非CIN和CINⅠ的2～4倍。（3）hTERC扩增在HPV阳性与阴性组分别为28.99%与3.57%,两组比较差异有统计学意义（P〈0.01）;非CIN组51例中,不伴有HPV感染的21例无hTERC扩增;CINⅠ与CINⅡ/Ⅲ组不伴HPV感染者各仅有1例hTERC扩增。结论 HPV载量和hTERC扩增均与CIN病变程度密切相关;hTERC扩增主要发生在HPV阳性病例,且与高度宫颈上皮内瘤变的关系更为密切,有望作为早期子宫颈癌及癌前病变的生物学标记物。

The relationship between the HPV load,hTERC gene and cervical lesions

Objective To study the relationship between the HPV load,hTERC gene and cervical intraepithelial neoplasia （CIN） in cervical exfoliated cells.Methods There were diagnosed as CINⅠ105,CINⅡ/Ⅲ 59 and cervical cancer 10 in the center for early diagnosis and treatment of cervical cancer of Peking university Shenzhen hospital,and 51 cases of non-CIN （normal or inflammation） as control.All subjects’ cervical exfoliated cells were examined with high-risk human papillomavirus （HR-HPV） testing using hybrid capture Ⅱ （HC-Ⅱ） and hTERC gene detection using fluorescence in situ hybridization （FISH）.Results （1） The positive rates of HPV infection were non-CIN 58.82%,CINⅠ67.62%,CIN Ⅱ/Ⅲ 98.31% and cervical cancer 100.00%,compared results were significantly different （P 〈0.01） ;the mean of HPV load were non-CIN 135.67,CINⅠ345.04,CINⅡ/Ⅲ 535.08 and cervical cancer 612.62,HPV load of CINⅡ/Ⅲ and cervical cancer are higher than non-CIN ’s （P 〈 0.05）.The positive rate of HPV infection and the mean of HPV load increased progressively along with the severity of histological grade.（2） The rates of hTERC gene amplification were non-CIN 3.92%,CINⅠ5.71%,CINⅡ/Ⅲ 57.63% and cervical cancer 90.00%,compared results were significantly different （P 〈 0.01） ;There was a marked increase of hTERC amplification in patients with CINⅡand above lesion （P 〈 0.01）,their rates were 10-15 times non-CIN and CINⅠ’s.The mean of hTERC gene amplification were non-CIN 6.50,CINⅠ9.00,CIN Ⅱ/Ⅲ 17.81 and cervical cancer 36.50,it increased progressively along with the severity of histological grade,there was no difference between CINⅠand non-CIN,but other compared results were significantly different （P 〈 0.01）.The mean of hTERC gene amplification in CINⅡ/Ⅲ and cervical cancer was 2-4 times non-CIN and CINⅠ’s.（3） The positive rates of hTERC gene amplification were 28.99% in HPV positive and 3.57% in HPV negative,compared results were significantly different （P 〈 0.01） ;51 cases in non-CIN,there was no one with hTERC gene amplification in 21 cases without HPV infection;there was only one case with hTERC gene amplification respectively in CIN Ⅰ and CIN Ⅱ/Ⅲ without HPV infection.Conclusions There was a tight correlation between HPV load,amplification of hTERC and CIN;amplification of hTERC were mainly found in the cases with HPV infection,and had a tight correlation with high grade CIN,it might be as a prognostic biomarker to judge whether there was high grade CIN or not.