高危型人乳头瘤病毒E6/E7 mRNA检测在宫颈病变筛查中的应用

Application of high risk-human papillomavirus E6/E7 mRNA detection in cervical lesions screening

目的探讨高危型人乳头瘤病毒(HR-HPV)E6/E7mRNA检测法,在宫颈病变筛查中的临床价值。方法选择2013年1月至2015年12月,在青岛市市立医院及青岛市城阳人民医院妇科门诊进行宫颈癌联合筛查,并进行阴道镜宫颈活组织检查的1 659例女性受试者为研究对象。统计学比较不同病理学检查结果中,第二代杂交捕获技术(HC2)法、HPV基因分型法及HPV E6/E7mRNA检测法3种HPV检测方法检测的HPV阳性率变化及其差异,并对HPV E6/E7mRNA检测法与HPV检测的金标准HC2法,在宫颈上皮内瘤变(CIN)2+(对宫颈病变病理学诊断结果≥CIN2者,则记为CIN2+)患者中HPV阳性率的诊断一致性进行分析。本研究与所有受试者签署知情同意书,研究方案及试验设计经过青岛市市立医院及青岛市城阳区人民医院院伦理委员会批准。结果 (1)3种HPV检测方法在不同宫颈活组织检查结果中的HPV阳性率两两比较结果均显示,HPV阳性率在正常或CIN1中,均低于CIN2或3,并且差异均有统计学意义(P<0.05);而在CIN2与3之间比较,差异无统计学意义(P>0.05)。HPV E6/E7mRNA检测法的HPV阳性率在CIN1中显著高于正常宫颈组织,并且差异有统计学意义(P<0.05)。(2)仅在病理学结果为正常宫颈组织中,HPV E6/E7mRNA检测法的HPV阳性率(61.4%)低于HC2法(73.7%)或HPV基因分型法(77.3%),并且差异有统计学意义(P<0.05)。(3)HC2法和HPV E6/E7 mRNA检测法在CIN2+患者中HPV阳性率的粗符合率为82.6%(100/121),Kappa值为0.69。结论 HPV E6/E7mRNA检测法较HC2法,能更好反映宫颈病变的程度。这2种检测方法在宫颈病变CIN2+中HPV阳性率的诊断一致性较好。

ObjectiveTo explore the clinical value of high risk-human papillomavirus（HR-HPV） E6/E7 mRNA detection in cervical lesion screening.MethodsFrom January 2013 to December 2015, a total of 1 659 women for cervical co-testing screening and cervical biopsy through colposcopy referral in gynecology clinic service of Qingdao Municipal Hospital Affiliated to Qingdao University and Qingdao Chengyang People′s Hospital, were chosen as study subjects. The changes and differences of HPV positive rates among 3 HPV detection methods including hybrid capture （HC）2, genotyping of HPV and HPV E6/E7 mRNA detection were compared statistically in different pathologic results. Analyzed the diagnostic consistency of HPV positive rates in cervical intraepithelial neoplasia （CIN）2＋ （if levels of cervical lesions by pathological diagnosis≥CIN2, showed as CIN2＋ ） between HPV E6/E7 mRNA detection and HC2 which is the gold standard of HPV detection method. All women signed informed consents, research program and experimental design were approved by Ethics Committee of Qingdao Municipal Hospital Affiliated the Qingdao University and Qingdao Chengyang People′s Hospital.Results①The multiple comparison of HPV positive rates of the 3 HPV detection methods in different cervical biopsies showed that, HPV positive rates in normal cervical tissue or CIN1 were all lower than those of CIN2 or CIN3, and the differences were statistically significant （P〈0.05）, but there was no significant difference between CIN2 and CIN3 （P〉0.05）. The HPV positive rate of HPV E6/E7 mRNA detection in CIN1 was higher than that of normal cervical tissue, and the difference was statistically significant （P〈0.05）. ②Only in normal cervical tissue, the HPV positive rate of HPV E6/E7 mRNA detection （61.4%） was lower than that of HC2 （73.7%） or HPV genotype （77.3%）, and the differences were statistically significant（P〈0.05）. ③In CIN2＋ patients, the crude coincidence rate of HPV positive rates between HC2 and HPV E6/E7 mRNA detection was 82.6% （100/121） and Kappa value was 0.69.ConclusionsHPV E6/E7 mRNA detection can reflect the degree of cervical lesions better than HC2. The consistency of HPV positive rates between HPV E6/E7 mRNA detection and HC2 detection in cervical lesions of CIN2＋ is good.