HPV L1壳蛋白与hTERC基因检测及联合分析对宫颈癌筛查的意义

Screening of Cervical Cancer by Combined Detection of Papillomavirus L1 Capsid Protein and Human Telomerase RNA Component

目的探讨人乳头状瘤病毒(HPV)L1壳蛋白和人端粒酶RNA(hTERC)基因在宫颈脱落细胞中的表达及联合分析对宫颈癌筛查的意义。方法收集2008年1月至2009年5月北京大学深圳医院宫颈门诊就诊患者的宫颈脱落细胞标本309例,用免疫细胞化学法检测HPV L1壳蛋白的表达,荧光原位杂交(FISH)方法检测hTERC基因的表达。结果①随着组织学诊断级别的升高,HPV L1壳蛋白阳性表达率呈下降趋势,与宫颈病变的严重程度呈负相关(rs=-0.272,P<0.01);而hTERC阳性表达率呈增加趋势,与宫颈病变的严重程度呈正相关(rs=0.605,P<0.01)。②4种HPV L1/hTERC表达类型的构成与宫颈病变的级别有关。L1(-)/hTERC(+)表达类型在CIN2以上病变中的比例明显高于在CIN1中(P<0.01);L1(+)/hTERC(-)及L1(-)/hTERC(-)与宫颈病变的级别呈负相关(P<0.01),L1(-)/hTERC(+)与宫颈病变的级别呈正相关(P<0.01);从L1(-)/hTERC(-)、L1(+)/hTERC(-)、L1(+)/hTERC(+)到L1(-)/hTERC(+)在各级病变中的构成比有随宫颈病变级别增高而增加的趋势(P<0.01)。③HPVL1和hTERC联合检测的阴性预测值高于单用HPV L1或hTERC(P<0.05),但三者对宫颈癌筛查效率的差异无统计学意义(P>0.05)。结论 HPV L1壳蛋白和hTERC基因可作为早期诊断及预测宫颈病变的标志物。从L1(-)/hTERC(-)、L1(+)/hTERC(-)、L1(+)/hTERC(+)到L1(-)/hTERC(+),这种表达时序可能反映了宫颈病变的发展过程。

Objective To evaluate the expression of human papillomavirus（HPV） L1 capsid protein and human telomerase RNA component（hTERC）in cytologic specimens of cervix and their combined analysis for cervical cancer screening. Methods The HPV L1 caspid protein in cytologic specimens of cervix was detected by using immunochemistry and hTERC by using fluorescence in situ hybridization（FISH）in 309 women treated in Shenzhen Hospital of Peking University from Jan. 2008 to May 2009. Results （DThe positive expression rate of HPV L1 was decreased and negatively correlated with the severity of cervical lesions（rs = -0. 272, P〈0. 01 ）, whereas the positive expression rate of hTERC was increased and positively correlated with the severity of cervical lesions（rs =0. 605, P〈0. 01 ）. ②The percentage of HPV L1 （-）/hTERC（ 4-）expression type in cervical intraepithelial neoplasia（CIN）grade 2 or worse was statistically higher than that in CIN1 grade（P〈0.01）, HPV L1 （＋）/hTERC （ - ）and HPV LI（ - ）/hTERC（ - ）were negatively correlated with the severity of cervical lesions（P〈0.01） ,whereas HPV L1 （-）/hTERC（ ＋ ）were positively correlated with the severity of cervical lesions（P〈0.01 ）. The expression from HPV L1 （-）/ hTERC（ - ）, HPV L1 （ ＋ ）/hTERC（ - ）, HPV L1 （＋）/hTERC（ ＋ ）, to HPV L1 （ - ）/hTERC（ ＋ ） had an increased tendency with the severity of cervical lesions（P〈0.01）. ③The negative predictive values of combining HPV L1 with hTERC were statistically higher than those of HPV L1 or hTERC alone（P〈0. 05）, but there was no significant difference in diagnostic efficien- cy for cervical cancer among combined detection of HPV L1 with hTERC, HPV L1 or hTERC alone（P〉0.05）. Conclusion HPV 1.1 and hTERC are useful markers for the early diagnosis of cervical lesion and prognostic prediction. The sequence of expression from HPV LI（-）/hTERC（-）, HPV L1 （＋）/hTERC（-）, HPV LI（＋）/hTERC（＋）,to HPV LI（-）/hTERC （＋）may reflect the progress process of cervical lesion.