HPV E6/E7 mRNA检测在LBC-/HPV+女性临床管理中的应用价值

Application value of HPV E6/E7 mRNA in the clinical management of HPV positive women with negative cervical cytology

目的:探讨HPV E6/E7 mRNA检测在LBC-/HPV+女性临床管理中的应用价值。方法:收集2017年12月至2019年9月在临沂市人民医院自愿接受液基细胞学(LBC)联合HR-HPV DNA(包含HPV16/18分型)或HPV E6/E7 mRNA检测进行宫颈癌筛查,结果为LBC-/HPV+且后续转诊阴道镜及组织病理学检查患者628例,以病理诊断结果为金标准,分析比较两种HPV检测方法对LBC-/HPV+患者人群发生高级别及以上宫颈病变(≥HSIL)的风险预测能力。结果:628例LBC-/HPV+患者中,共检出≥HSIL患者80例(12.74%),其中以30~39岁组检出率最高(17.89%)。490例HR-HPV DNA阳性患者≥HSIL总检出率为10.00%(49/490),双+组检出率最高(14.89%,14/94);138例HPV E6/E7 mRNA阳性患者≥HSIL总检出率为22.46%(31/138),16/18/45+组检出率最高(37.78%,17/45)。HPV E6/E7 mRNA阳性组发生≥HSIL的相对危险度(RR值)是HR-HPV DNA阳性组的2.246倍(95%CI为1.493~3.379);16/18/45+组发生≥HSIL的RR值是16/18+组患者的3.169倍(95%CI为1.786~5.622);HPV E6/E7 mRNA其余11型+组发生≥HSIL的RR值是HR-HPV DNA其余12型+组的2.170倍(95%CI为1.115~4.222),差异均有统计学意义(P<0.05)。结论:HPV E6/E7 mRNA检测尤其是16/18/45分型检测是LBC-/HPV+患者人群发生≥HSIL的有效风险预测指标,其评价效能优于包含HPV16/18分型的HR-HPV DNA检测;HPV E6/E7 mRNA有望作为HR-HPV DNA阳性但16/18分型阴性患者的进一步分流指标。

Objective:To investigate the application value of HPV E6/E7 mRNA in the clinical management of women with HPV positive and negative cervical cytology.Methods:628 cases of female patients with LBC-/HPV+(negative liquid-based cytology/HPV positive)undergone subsequent referral colposcopy and histopathological examination were collected from December 2017 to September 2019 in Linyi People's Hospital,who had voluntarily accepted cervical cancer screening of LBC combined with high-risk human papillomavirus(HR-HPV)DNA including HPV16/18 genotyping or HPV E6/E7 mRNA.Taking pathological diagnosis as gold standards,the ability of two methods for HPV detection to predict the incidence risk of high-grade squamous intraepithelial lesion(HSIL)or worse(≥HSIL)in LBC-/HPV+patients was analyzed and compared.Results:In 628 cases of patients with LBC-/HPV+,80 cases(12.74%)of≥HSIL were detected,and the detection rate of≥HSIL in 30~39 years was the highest(17.89%).The total detection rate of≥HSIL in 490 patients with HR-HPV DNA positive and in 138 patients with HPV E6/E7 mRNA positive was 10.00%(49/490)and 22.46%(31/138),respectively.In the above two groups,the highest detection rate of≥HSIL was in HPV16/18 and 12 other HR-HPV positive group(14.89%,14/94)and in HPV16/18/45 positive group(37.78%,17/45),respectively.The relative risk(RR)of≥HSIL incidence of HPV E6/E7 mRNA positive group was 2.246 times(95%CI:1.493~3.379)of HR-HPV DNA positive group,which of HPV 16/18/45 positive group was 3.169 times(95%CI:1.786~5.622)of HPV 16/18 positive group and 11 other HR-HPV E6/E7 mRNA positive group was 2.170 times(95%CI:1.115~4.222)of 12 other HR-HPV DNA positive group.The difference was statistically significant(P<0.05).Conclusion:HPV E6/E7 mRNA,especially the 16/18/45 genotyping,is an effective risk prediction index of≥HSIL in the patients with LBC-/HPV+.The evaluation efficiency is superior to that of HR-HPV DNA including HPV16/18 genotyping.Hopefully,HPV E6/E7 mRNA could be used as a further triage index for LBC-/HPV+patients with HPV16/18 negative.