HPV分型定量检测对宫颈病变的预测价值

The value of HPV genotyping and quantitative PCR testing in the prediction of cervical lesions

目的:探讨人乳头瘤病毒(HPV)分型定量检测对宫颈病变的预测价值。方法:2045例宫颈病变患者组织病理学检查诊断为宫颈炎695例、宫颈上皮内瘤变(CIN)I 247例、CINII 294例、CINIII 407例、宫颈癌(CC)402例。实时定量荧光PCR法(硕世21 HPV分型定量检测系统)检测高危型(HR)-HPV分型及病毒载量。采用ANOVA检验分析病毒载量与宫颈病变之间的关系。应用ROC曲线的方法确定预测CINII+的cut off值。结果:CIN人群中最常见的HPV感染亚型依次为HPV16、58、33、52、31、18。CIN及CC中最常见的HPV感染亚型依次为HPV16、58、33、52、18、31。随着宫颈病变级别的增加,HPV16、18亚型病毒载量的中位值随之增加,差异有统计学意义(P<0.001)。HPV16/18型临床cut off值分别为1.59×104拷贝数/104细胞和1.56×104拷贝数/104细胞时,可预测HPV16、18型感染患者患有CINII+的敏感性分别为77.93%和79.26%,特异性分别为53.51%和67.82%。结论:在中国除了HPV16、18亚型外,HPV33、52、58型感染也应受到重视。HPV病毒载量作为宫颈癌风险标记物具有型别依赖性,通过获取HPV16、18基因型载量的合适阈值,可对CINII+做出风险提示和最佳预测。

Objective： To explore the value of human papillomavirus（ HPV） genotyping and quantitative PCR testing for cervical lesions.Methods： 2045 patients with cervical lesions were diagnosed by pathological examination,695 cases of cervicitis,247 cases of cervical intraepithelial neoplasia（ CIN） I,294 cases of CIN II,407 cases of CIN III,402 cases of cervical cancer（ CC）.The genotyping and viral load of high-risk HPV were detected by using real-time quantitative fluorescence PCR analysis（ Bio Perfectus Multiplex Real Time,BMRT）.The relationship between viral load and cervical lesions was analyzed by ANOVA test,and the cut off value of CINII＋ was determined by using ROC curve.Results： The most common HPV genotypes in cervical lesions were HPV16、58、33、52、31、18.The most common HPV genotypes in CIN and CC patients were HPV16、58、33、52、31、18.The median values of viral load of HPV16/18 genotype increased with the degree of cervical lesions,which had significant difference（ P〈0.001）.Moreover,it could predict that sensitivity and specificity value for CINII＋ infected by HPV16/18 genotype were 77.93% and 79.26%,53.51% and 67.82% when cut off values achieved 1.59×10~4 copies/104 cells for HPV16 and 1.56×10~4 copies/10~4 cells for HPV18. Conclusions： In addition to HPV16、18,HPV33、52、58 infections should also be taken seriously in China.The viral load as cervical cancer risk markers is type-dependent.Obtaining of suitable threshold of HPV16/18 genotypes load,accompanied by HPV genotyping and quantitative PCR testing,could apply to risk warning of CINII＋.