HR-HPV载量和HR-HPV E6/E7 mRNA在宫颈癌和癌前病变的表达和意义

目的比较和分析高危型人乳头瘤病毒(HR-HPV)载量和HR-HPV E6/E7 mRNA在宫颈癌和宫颈上皮内瘤变(CIN)的表达和差异,探讨二者的关联及其在宫颈癌变进程中的临床意义。方法以339例HR-HPV持续感染者为研究对象,依病理组织学诊断分为宫颈癌和CINⅠ、CINⅡ、CINⅢ共4组,分别采用PCR荧光法、支链DNA技术定量检测宫颈刷检物中的HPV-DNA和HPV E6/E7 mRNA,对数据资料进行统计学分析。结果(1)随宫颈病变严重程度的增加,HR-HPV DNA和HR-HPV E6/E7 mRNA的表达水平和阳性表达率均明显上升;(2)不同等级的宫颈病变中,HR-HPV DNA和HR-HPV E6/E7 mRNA的阳性表达率总体分布差异无统计学意义(P>0.05),两两比较显示,除CINⅡ组两指标检测阳性率差异无统计学意义(P>0.05),其余各组间差异有统计学意义(P<0.05);(3)4组患者HPV E6/E7 mRNA和HR-HPV DNA的总体表达水平差异均有统计学意义(P<0.05),两两比较显示:HPV E6/E7 mRNA在CINⅢ和宫颈癌之间差异无统计学意义(Z=-1.013,P=0.311),其余组别间差异有统计学意义(P<0.05)。HR-HPV DNA在CINⅠ和CINⅡ之间差异无统计学意义(Z=-1.376,P=0.169),CINⅢ和宫颈癌之间差异无统计学意义(Z=-0.991,P=0.322),其余组别间差异有统计学意义(P<0.05);(4)HPV E6/E7 mRNA和HR-HPV DNA间存在相关性(r=0.533,P<0.05),不同级别病变表现为在CINⅠ、CINⅡ呈明显正相关(r=0.412,0.804,均P<0.05),在CINⅢ和宫颈癌无相关性(P>0.05);(5)随着病毒载量的提高,高级别CIN和宫颈癌在宫颈病变整体构成的占比上升。结论 HR-HPV E6/E7 mRNA在CINⅠ阶段即开始表达,随着表达量激增,加速宫颈癌的发生,HR-HPV载量和HR-HPV E6/E7 mRNA存在显著相关性,病毒与宿主基因整合,干扰了HPV载量与病变严重程度的一致性。

Expression and significance of HR-HPV load and HR-HPV E6/E7 mRNA in cervical cancer and precancerous lesions

Objective To compare and analyze the expression and difference of high risk human papillomavirus (HR-HPV) load and HR-HPV E6/E7 mRNA in cervical carcinoma and cervical intraepithelial neoplasia (CIN). Methods Totally 339 patients with persistent HR-HPV infection were divided into 4 groups according to histopathological diagnosiscervical cancer, CINⅠ,CINⅡ and CINⅢ HPV-DNA and HPV E6/E7 mRNA from cervical swab were detected by PCR fluorescence assay and branched-chain DNA technique,respectively. The data were analyzed statistically. Results (a) As the severity of cervical lesions increased,the expression level and positive rate of HR-HPV DNA and HR-HPV E6/E7 mRNA increased significantly;(b) There was no significant difference in the positive expression rate of HR-HPV DNA and HR-HPV E6/E7 mRNA between different grades of cervical lesions (P>0.05),and comparing with each other,the positive rate of the two indexes in the CINⅡ group was the same,the difference between the other groups was significant (P <0.05);(c) The expression levels of HPV E6/E7 mRNA and HR-HPV DNA in the four groups were significantly different (P<0.05). There was no significant difference in HPV E6/E7 mRNA between CINⅢ and cervical cancer (Z=-1.013,P=0.311),but there was significant difference among other groups (P<0.05). There was no significant difference in HR-HPV DNA between CINⅠand CINⅡ(Z= -1.376,P=0.169),CINⅢ and cervical cancer (Z=-0.991,P=0.322),but there was significant difference between other groups (P<0.05);(d) There was a significant grade correlation between HPV E6/E7 mRNA and HR-HPV DNA (r=0.533,P<0.05). There was a significant positive correlation between CINI and CINⅡ (r=0.412,0.804,all P >0 05). There was no correlation between CINⅢ and cervical cancer (all P>0.05). (e) With the increase of viral load,the proportion of high-grade CIN and cervical cancer in the over all composition of cervical lesions increased. Conclusion HR-HPV E6/E7 mRNA began to express in the CINⅠ phase,which accelerated the occurrence of cervical cancer with the increase of the expression level. There was a significant correlation between HR-HPV load and HR-HPV E6/E7 mRNA. The integration of virus and host gene interfered with the consistency between HPV load and severity of lesion.