E6/E7 mRNA检测在宫颈癌高危人群HPV分流的应用
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摘要
目的探讨采用E6/E7 mRNA检测方法对于CIN1及以下病变的宫颈癌高危人群HPV阳性分流的可行性。方法选择2016年1—6月山西省古交市、北京市密云县和河北省曲周县在2014年政府免费宫颈癌筛查中发现的322例诊断为宫颈上皮内病变(CIN1)及以下病变作为研究对象,进行HPV PCR分型检测,其中高危HPV阳性者再进行宫颈细胞学检查和E6/E7 mRNA检测,任一阳性者进行阴道镜检查,并对阴道镜检查可疑或异常者进行定点活检和组织病理学检查。结果 322例患者中,高危型HPV阳性检出率为34.2%(110/322),其中80例(72.7%)为单一HPV高危亚型阳性,主要感染型别前三位分别为HPV52、HPV16和HPV58。宫颈细胞学分流检出CIN2及以上病变2例(1.8%,2/110)。E6/E7 mRNA分流检出CIN2及以上病变5例,检出率为4.6%。在E6/E7 mRNA阳性患者中CIN2及以上为5例(14.3%);E6/E7 mRNA阴性患者中,CIN2及以上患者为3例(4.0%),两组比较,差异无统计学意义(P=0.066)。结论对于HPV阳性者采用E6/E7 mRNA分流宫颈癌前病变的检出率高于细胞学分流,可应用于宫颈癌高危人群HPV阳性的分流。
Objective To explore the feasibility of E6/E7 mRNA test in the triage of HPV positive women with CIN1 and below. Methods From January to June 2016, 322 cases diagnosed with CIN1 and below in Qujiao county, Miyun county and Quzhou county during the free cervical cancer screening in 2014 were selected. HPV PCR typing was performed, among which cervical cytology and E6/E7 mRNA were performed for high-risk HPV positive patients, colposcopy was performed for any positive patients, site-specific biopsy and histopathological examination were performed for those with suspicious or abnormal colposcopy. Results Among the 322 patients, the positive detection rate of high-risk HPV was 34.2%(110/322),among which 80(72.7%) were single high-risk HPV subtype positive, and the first three major infection types were HPV52,16 and 58, respectively. Using cytology triage test detected 2 cases of CIN2 +(1.8%,2/110), Using E6/E7 mRNA triage test detected 5 cases of CIN2 +, the detective rate was 4.6%. CIN2 + were found in 5 cases of E6/E7 mRNA positive patients(14.3%); Among the patients with negative E6/E7 mRNA, 3 patients(4.0%) had CIN2 +, and the difference was not statistically significant(P=0.066). Conclusions For HPV positive patients, the detection rate of E6/E7 mRNA was higher than cytology triage, which can be applied in the triage of HPV positive high-risk cervical cancer population.
Objective To explore the feasibility of E6/E7 mRNA test in the triage of HPV positive women with CIN1 and below. Methods From January to June 2016, 322 cases diagnosed with CIN1 and below in Qujiao county, Miyun county and Quzhou county during the free cervical cancer screening in 2014 were selected. HPV PCR typing was performed, among which cervical cytology and E6/E7 mRNA were performed for high-risk HPV positive patients, colposcopy was performed for any positive patients, site-specific biopsy and histopathological examination were performed for those with suspicious or abnormal colposcopy. Results Among the 322 patients, the positive detection rate of high-risk HPV was 34.2%(110/322),among which 80(72.7%) were single high-risk HPV subtype positive, and the first three major infection types were HPV52,16 and 58, respectively. Using cytology triage test detected 2 cases of CIN2 +(1.8%,2/110), Using E6/E7 mRNA triage test detected 5 cases of CIN2 +, the detective rate was 4.6%. CIN2 + were found in 5 cases of E6/E7 mRNA positive patients(14.3%); Among the patients with negative E6/E7 mRNA, 3 patients(4.0%) had CIN2 +, and the difference was not statistically significant(P=0.066). Conclusions For HPV positive patients, the detection rate of E6/E7 mRNA was higher than cytology triage, which can be applied in the triage of HPV positive high-risk cervical cancer population.
引文
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[12]胡尚英,赵方辉,马俊飞,等.轻度宫颈上皮内瘤变预后及其与人乳头状瘤病毒关系的前瞻性队列研究[J].中华预防医学杂志,2014,48(5):361-365.
[2]Ndiaye C,Mena M,Alemany L,et a1.HPV DNA,E6/E7mRNA,and P16INK4a detection in head and neck cancers.a systematic review and meta-analysis[J].Lancet Oncol,2014,15(12):1319-1331.
[3]Rodrigues DA,Pereira R,Oliveira LS,et al.Prevalence of cytological atypia and high-risk human papillomavirus infection in Panaráindigenous women in Central Brazil[J].Cad Saude Publica,2014,30(12):2587-2593.
[4]Theodoros A,Kimon C,Theodoros M,et al.Human papillomavirus E7 protein detection as a method of triage to colposcopy of HPV positive women,in comparison to genotyping and cytology.Final results of the PIPAVIR study[J].Int J Cancer,2017,141(3):519-530
[5]曾冰微,黄种心,张东妹.高危型HPV E6/E7 mRNA在宫颈病变筛查中的价值探讨.中国妇产科临床杂志,2018,19(1):9-11.
[6]沈洁,高丽丽,张月,等.北京市宫颈癌筛查妇女中高危型HPV感染状况及在宫颈癌前病变中的分布[J].中华预防医学杂志,2018,52(5):493-497.
[7]张小松,毕蕙,周敏,等.农村地区不同宫颈癌筛查方法的比较研究[J].中国妇产科临床杂志,2016,17(6):498-500.
[8]Rhake R,Hu SY,Zhao S.Eight-type human papillomavirus E6/E7 oncoprotein detection as a novel and promising triage strategy for managing HPV positive women[J].Int J Cancer,2019,144(1):34-42.
[9]张小松,周敏,郝波,等.中东部3县7138例农村妇女宫颈癌筛查分析[J].中国妇幼健康研究,2016,27(5):574-576.
[10]Liu QL,Lin XX,Lin LY,et al.A comparative study of three different nucleic acid amplification techniques combined with microchip electrophoresis for HPVl6 E6/E7 mRNA detection[J].Analyst,2015,140(19):6736-6741.
[11]Ratnam S,Coutlee F,Fontaine D,et al.Clinical performance of the pretect HPV proofer E6/E7 mRNA assay in comparison with that of the Hybrid Capture 2 test for identification of women at risk of cervical cancer[J].J Clin Micrebiol,2010,48(8):2779.
[12]胡尚英,赵方辉,马俊飞,等.轻度宫颈上皮内瘤变预后及其与人乳头状瘤病毒关系的前瞻性队列研究[J].中华预防医学杂志,2014,48(5):361-365.