E6/E7 mRNA检测筛查妊娠期高危型人乳头瘤病毒感染的价值研究

背景妊娠期高危型人乳头瘤病毒（HR-HPV）感染及宫颈病变需要更为有效的诊断与分流管理措施，从而指导个性化诊疗，减少妊娠期非必要有创检查。目的将妊娠期HR-HPV感染E6/E7 mRNA检测与HR-HPV DNA检测进行比较，评估E6/E7 mRNA检测应用于妊娠期HR-HPV感染及宫颈病变的诊断价值。方法选取2016年1月至2019年1月在首都医科大学宣武医院妇产科建档定期产检的符合纳入标准的20~45岁育龄妊娠期女性为研究对象，分别进行薄层液基细胞学检测（TCT）及HR-HPV DNA检测，结果异常者进一步行阴道镜检查并取活组织送病理检查（以病理检查结果为金标准），同时留取宫颈脱落细胞检测HR-HPV E6/E7 mRNA片段。病理检查结果为宫颈上皮内瘤变（CIN）Ⅱ级、CINⅢ级定义为宫颈高级别病变。结果本研究共调查20~45岁健康单胎妊娠女性1 058名，其中TCT结果异常和/或HPV 16、18亚型者118名，同意行阴道镜检测并成功获得病理检查结果者84名。在病理检查结果为CINⅠ及正常或炎症的女性中，HR-HPV E6/E7 mRNA检测阳性率均低于HR-HPV DNA检测（P<0.05）；在病理检查结果为CINⅡ级及CINⅢ级的女性中，HR-HPV E6/E7 mRNA、HR-HPV DNA检测阳性率比较，差异无统计学意义（P>0.05）。HR-HPV DNA预测宫颈高级别病变的灵敏度为89.7%（26/29），特异度为21.8%（12/55），阳性预测值为37.1%（26/69），阴性预测值为75.0%（12/15）；HR-HPV E6/E7 mRNA预测宫颈高级别病变的灵敏度为65.5% （19/29），特异度为54.5%（25/55），阳性预测值为43.0%（19/44），阴性预测值为75.0%（25/40）。McNemar配对χ2检验结果显示：HR-HPV E6/E7 mRNA预测宫颈高级别病变的灵敏度低于HR-HPV DNA，特异度高于HR-HPV DNA（P<0.05）。结论HR-HPV E6/E7 mRNA检测可以在一定程度上提高CINⅡ级及以上宫颈高级别病变的诊断特异度，因而可以考虑将HR-HPV E6/E7 mRNA检测应用于HR-HPV阳性病例的筛查分流管理，避免妊娠期非必要有创检查。

Clinical Evaluation of High-risk HR-HPV E6/E7 mRNA Detection during Pregnancy

Background It is necessary to differentiate high-risk human papillomavirus(HR-HPV)infection and cervical lesions during pregnancy using an effective measure,so as to guide personalized diagnosis and treatment and to reduce unnecessary invasive examinations during pregnancy.Objective To assess the value of HR-HPV E6/E7 mRNA detection in differentiating HR-HPV infection and cervical lesions during pregnancy by comparing efficacy between it and HR-HPV DNA testing.Methods Participants were healthy women with singleton pregnancy(20-45-years old)selected from Department of Obstetrics and Gynecology of Capital Medical University Xuanwu Hospital during January 2016 to January 2019.All had file creation and underwent regular prenatal examination,and those with abnormal liquid-based cytology and HR-HPV DNA testing results further underwent colposcopy with biopsy taken for pathological examination(serving as a gold standard),and performed HR-HPV E6/E7 mRNA detection in cervical exfoliated cells collected as samples.Pathologically detected CINⅡandⅢwere defined as high-grade cervical lesions.Results Of the 1058 participants,118 had cytological abnormalities and/or HPV 16 and 18 infections,and 84 of them consented to perform colposcopy with biopsy pathological results successfully obtained.The prevalence of HR-HPV E6/E7 mRNA positivity was lower than that of HR-HPV DNA positivity in women with CINⅠ,normal cervical epithelium or cervicitis detected by pathological examination(P<0.05).In contrast,the prevalence of HR-HPV E6/E7 mRNA positivity was similar to that of HR-HPV DNA positivity in those with CINⅡandⅢdetected by pathological examination without statistical difference(P>0.05).In predicting CINⅡandⅢ,the HR-HPV DNA testing had a sensitivity of 89.7%(26/29),a specificity of 21.8%(12/55),a positive predictive value of 37.1%(26/69),and a negative predictive value of 75.0%(12/29),and the HR-HPV E6/E7 mRNA detection had a sensitivity of 65.5%(19/29),a specificity of 54.5%(25/55),a positive predictive value of 43.0%(19/44),and a negative predictive value 75.0%(25/40).McNemar's test revealed that HR-HPV E6/E7 mRNA detection had a lower sensitivity but a higher specificity than HR-HPV DNA testing in diagnosing CINⅡandⅢ(P<0.05).Conclusion HR-HPV E6/E7 mRNA detection may have an increased specificity in diagnosing CINⅡandⅢthan HR-HPV DNA testing,so it may be used in HR-HPV positive cases for differentiating HR-HPV infections and cervical lesions to avoid unnecessary invasive examinations during pregnancy.