基因芯片法与杂交捕获法检测人乳头瘤病毒对比分析

Cross-Check Analysis between Detection of HPV by Gene Chip Test and Hybrid Capture 2

目的:评价杂交捕获法和基因芯片法检测宫颈人乳头瘤病毒(human papillomavirus,HPV)感染的方法学优势,探讨HPV的多重感染以及HPV病毒负荷量与不同级别宫颈病变的相关性。方法:分别采用基因芯片法和杂交捕获法对360例宫颈癌机会性筛查的患者进行HPV-DNA的检测以及液基细胞学检测,并以基因测序为金标准评价两种检测方法的灵敏度、特异度。结果:基因芯片法和杂交捕获法的灵敏度、特异度和约登指数分别为前者98.33%、93.40%和0.917,后者97.56%、98.17%和0.957。按宫颈液基细胞学检查结果分为NSIL组、ASC组、LSIL组及HSIL和SCC组,随宫颈细胞病变程度的增加,HPV感染率、高危型HPV感染率、多重感染率病毒逐渐增加,在宫颈上皮正常组与异常组间比较差异有统计学意义,低危型HPV感染率无规律性改变。结论:两种HPV检测方法相比,基因芯片法灵敏度较高,杂交捕获法特异度较高,基因芯片法可作为宫颈病变筛查方法;HPV的多重感染和病毒负荷量增加都与宫颈病变程度有一定的相关性。

Objective： To evaluate the methodological merits of the gene chip diagnostic test and Hybrid Capture 2 HPV DNA test in detecting the human cervical papillomavirus （HPV） infection and to investigate the association between multiple-infection, viral load of HPV and cervical lesions at various stages. Methods： During the period from January to December 2009, 360 female participants were screened for HPV using the gene chip diagnostic test and Hybrid Capture 2 test. They were also screened for cervical cancer using the Thin-prep cytology test （liquid-based cytology）. DNA sequencing was used as the gold standard to evaluate the sensitivity and specificity of the two detection tests. Results： The sensitivity, specificity and Youden＇s index were respectively 98.33%, 93.40% and 0.917 in the genotyping diagnostic test and 97.56%, 98.17% and 0.957 in the Hybrid Capture 2 method. Based on the result of the cervical liquid-based cytology test, the cases were divided into the NSIL, ASC and LSIL groups, as well as the HSIL and SCC groups. The HPV infection rate, high and low-risk HPV infection rates, multi-infection rate and viral load increased with the aggravation of cervical squamous intraepithelial lesions. There were statistical differences between the groups with normal cervical squamous epithelium and with diseased tissue. However, there was no regular pattern in the changes of the low-risk HPV infection rate. Conclusions： In a comparison of the two HPV detection tests, there is a higher sensitivity in the genotyping diagnostic test, and a higher specificity in the Hybrid Capture 2 test. The gene chip test or TCT can additionally be used in cervical cancer screening, potentially making them more useful than the Hybrid Capture 2 test. The multi-infection rate of HPV and increase of the viral load are both associated with the severity of the cervical lesion.