Rebolj M, Njor S, Lynge E, Preisler S, Ejegod D, Rygaard C, Bonde J
Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
Cytopathology. 2017 Oct;28(5):419-428. doi: 10.1111/cyt.12451.
We studied how representative cytologically abnormal women ("referral populations") are with respect to uncovering differences between human papillomavirus (HPV) assays in the primary screening where most women are cytologically normal.
A total of 4997 women were tested with SurePath® cytology, and Hybrid Capture 2 (HC2), cobas, CLART and APTIMA HPV assays. Women with positive test results were offered a follow-up. For all detected HPV infections and HPV-positive high-grade cervical intraepithelial neoplasia (≥CIN2), we studied the distributions of assay-specific signal strengths in the baseline samples as documented by the assays' automatically generated reports. We calculated the likelihood of test result discordance as the proportion of HPV-positive samples that were not confirmed by all four assays.
Median signal strengths for HPV infections were weaker in normal than abnormal cytology (P<.001, adjusted for women's age, multiple infections and the reason for taking the sample). For HC2, they were RLU/CO 11.0 (interquartile range, IQR: 3.3-52.8) vs 124.2 (IQR: 22.8-506.9), respectively; for cobas, Ct 33.5 (IQR: 29.6-37.5) vs 26.9 (IQR: 23.7-31.3), respectively; for APTIMA, S/CO 10.2 (IQR: 5.8-11.3) vs 11.1 (IQR: 9.4-15.5), respectively. Similar patterns were observed for HPV-positive ≥CIN2. The four HPV assays more frequently returned discordant test results in normal than in abnormal cytology. Relative frequency of discordance in detecting HPV infections was 0.39 (95% confidence interval: 0.33-0.48) for abnormal vs normal cytology.
These data suggest that referral population studies, by not including sufficient numbers of cytology normal women, underestimate the differences between HPV assays that would become apparent in primary screening.
我们研究了在大多数女性细胞学正常的初次筛查中，具有代表性的细胞学异常女性（“转诊人群”）在揭示人乳头瘤病毒（HPV）检测方法之间差异方面的情况。
对4997名女性进行了SurePath®细胞学检测、杂交捕获2代（HC2）、cobas、CLART和APTIMA HPV检测。检测结果呈阳性的女性接受了随访。对于所有检测到的HPV感染和HPV阳性的高级别宫颈上皮内瘤变（≥CIN2），我们研究了检测方法自动生成报告中记录的基线样本中各检测方法特异性信号强度的分布情况。我们将检测结果不一致的可能性计算为未被所有四种检测方法确认的HPV阳性样本的比例。
HPV感染的中位信号强度在细胞学正常的女性中比异常女性弱（P<0.001，根据女性年龄、多重感染和取样原因进行了调整）。对于HC2，分别为RLU/CO 11.0（四分位间距，IQR：3.3 - 52.8）和124.2（IQR：22.8 - 506.9）；对于cobas，Ct分别为33.5（IQR：29.6 - 37.5）和26.9（IQR：23.7 - 31.3）；对于APTIMA，S/CO分别为10.2（IQR：5.8 - 11.3）和11.1（IQR：9.4 - 15.5）。对于HPV阳性的≥CIN2也观察到了类似模式。这四种HPV检测方法在细胞学正常的女性中比在异常女性中更频繁地得出不一致的检测结果。异常与正常细胞学情况下检测HPV感染时不一致的相对频率为0.39（95%置信区间：0.33 - 0.48）。
这些数据表明，转诊人群研究由于未纳入足够数量的细胞学正常女性，低估了HPV检测方法在初次筛查中会显现出的差异。
