人乳头瘤病毒E6/E7 mRNA检测在宫颈非典型腺细胞中的应用及临床意义

Application and clinical significance of human papilloma virus E6/E7 mRNA detection in cervical atypical glandular cells

目的探讨人乳头瘤病毒(HPV)E6/E7mRNA检测在宫颈非典型腺细胞(AGC)中的应用及临床意义。方法收集大连医科大学附属大连市妇产医院2014年1月至2018年3月液基细胞学检查诊断为宫颈AGC患者445例,分析其组织学结果及HPVE6/E7mRNA检测结果,并比较HPVE6/E7mRNA阴性与阳性患者的组织学差异。结果445例宫颈AGC患者组织学结果显示,阴性306例(68.76%),有临床意义病变129例(28.99%)。445例宫颈AGC患者中,HPVE6/E7mRNA阳性121例(27.19%),其中HPV16和18/45型占HPVE6/E7mRNA阳性的54.55%(66/121);阴性324例(72.81%),其中组织学结果为子宫内膜病变及附件转移癌的13例宫颈AGC患者HPVE6/E7mRNA均为阴性。HPVE6/E7mRNA阴性宫颈AGC患者组织学结果阴性率明显高于HPVE6/E7mRNA阳性患者[91.05%(295/324)比9.09%(11/121)],差异有统计学意义(P<0.01);HPVE6/E7mRNA阳性患者组织学结果为原位腺癌(AIS)、高级别鳞状上皮内病变(HSIL)、宫颈腺癌的发生率明显高于HPVE6/E7mRNA阴性患者[40.50%(49/121)比1.23%(4/324)、44.63%(54/121)比1.23%(4/324)、3.31%(4/121)比0.31%(1/324)],差异有统计学意义(P<0.01)。HPVE6/E7mRNA检测诊断宫颈AGC患者有临床意义病变的敏感度为82.95%(107/129),特异度为95.57%(302/316),阳性预测值为88.43%(107/121),阴性预测值为93.21%(302/324)。结论宫颈AGC患者组织学结果阴性患者明显多于临床有意义病变。对于HPVE6/E7mRNA阴性的宫颈AGC患者,在除外宫颈外来源病变和充分评估宫颈病变的风险后,可适当采取保守方式随诊,而HPVE6/E7mRNA阳性宫颈AGC患者需要积极检查,及早发现病变并治疗。

Objective To investigate the application and clinical significance of human papilloma virus (HPV) E6/E7 mRNA detection in cervical atypical glandular cells (AGC). Methods Four hundred and forty-five cervical AGC patients diagnosed by thin-layer liquid-based cytology in the Maternity Affiliated Hospital of Dalian Medical University from January 2014 to March 2018 were collected. Histological follow-up data and HPV E6/E7 mRNA detection results were analyzed, and histological differences in HPV E6/E7 mRNA positive and negative patients were compared. Results The histological result of 445 patients with cervical AGC showed that negative was in 306 cases (68.76%), and clinical significant lesion was in 129 cases (28.99%). In 445 patients with cervical AGC, HPV E6/E7 mRNA result was positive in 121 cases (27.19%), among whom the positive rate of HPV 16 and 18/45 type was 54.55%(66/121);HPV E6/E7 mRNA result was negative in 324 cases (72.81%), including 13 non-cervical lesions. The negative rate of histological results in HPV E6/E7 mRNA negative patients was significantly higher than that in HPV E6/E7 mRNA positive patients: 91.05%(295/324) vs. 9.09%(11/121), and there was statistical difference (P<0.01);the rates of adenocarcinoma in situ (AIS), high-grade squamous intraepithelial lesion (HSIL) and cervical adenocarcinoma of histological result in HPV E6/E7 mRNA positive patients were significantly higher than those in HPV E6/E7 mRNA negative patients: 40.50%(49/121) vs. 1.23%(4/324), 44.63%(54/121) vs. 1.23%(4/324), 3.31%(4/121) vs. 0.31%(1/324), and there were statistical differences (P<0.01). The sensitivity of HPV E6/E7 mRNA in detecting clinical significant lesion of cervical AGC patients was 82.95%(107/129), the specificity was 95.57%(302/316), positive predictive value was 88.43%(107/121), and negative predictive value was 93.21%(302/324). Conclusions The histological result of cervical AGC shows that the amount of negative patients is significantly higher than clinical significant lesion. For cervical AGC patients with HPV E6/E7 mRNA negative results, conservative follow-up can be adopted after excluding extracervical lesions and fully assessing the risk of cervical lesions. However, the cervical AGC patients with HPV E6/E7 mRNA positive results need further examination to detect lesion and choose treatment earlier.