Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, non-inferiority trial
Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, non-inferiority trial
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人乳头瘤病毒检测对自我收集与临床医生收集的样本进行检测，以检测2级或更严重的宫颈上皮内瘤变：一项随机、配对筛查阳性、非劣效性试验
DOI：
10.1016/s1470-2045(18)30763-0
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发表时间：
2019-02-01
期刊：
影响因子：
51.1
通讯作者：
Berkhof, Johannes
中科院分区：
文献类型：
--
作者：
Polman, Nicole J.;Ebisch, Renee M. F.;Berkhof, Johannes
背景：人乳头瘤病毒（HPV）检测是对临床采集样本进行HPV检测的潜在替代方法，但其临床准确性在常规筛查人群中的非劣效性仍有待评估。改进研究是为了评估在有组织的筛查环境中自行收集样本的原发性HPV检测的临床准确性。在这项随机、非劣效性试验中，29-61岁的女性被邀请参加这项研究，作为荷兰定期筛查邀请的一部分。提供知情同意的妇女被随机分配（1:1，按年龄分层，块大小为10）到两组中的一组：自我抽样组，其中妇女被要求使用Evalyn刷子收集自己的宫颈阴道样本（Rovers医疗设备BV，奥斯，荷兰）；或以临床医生为基础的抽样组，其中样本由全科医生用Cervex-Brush （Rovers Medical Devices BV）收集。所有样本均采用经临床验证的GP5+/6+ PCR酶免疫分析法（Labo Biomedical Products BV, Rijswijk, Netherlands）检测HPV。两组hpv阳性妇女用另一种收集方法进行重新检测，并根据现行荷兰筛查指南通过细胞学和重复细胞学进行分类。主要终点是宫颈上皮内瘤变（CIN） 2级及以上（CIN2+）和3级及以上（CIN3+）的检测。对自行采集的HPV检测与临床采集的HPV检测的非劣效性进行了评估，相对敏感性为90%，相对特异性为98%。本研究已在荷兰试验登记册（NTR5078）登记并已完成。在被邀请参加的187473名妇女中，8212名被随机分配到自我抽样组，8198名被分配到临床医生抽样组。在排除了符合排除标准或未归还样本的妇女后，7643名妇女被纳入自抽样组，6282名妇女被纳入临床抽样组。569例（7.4%）自行采集的样本和451例（7.2%）临床采集的样本HPV检测呈阳性（相对危险度1.04 [95% CI 0.92-1.17]）。hpv阳性妇女的中位随访时间为20个月（IQR 17-22）。HPV检测的CIN2+敏感性和特异性在自取样和临床取样之间没有差异（相对敏感性0.96[0.90-1.03]；相对特异性1.00[0.99-1.01]）。CIN3+终点的相对敏感性为0.99(0.91-1.08)，相对特异性为1.00（0.99-1.01）。在检测CIN2+或CIN3+病变方面，用临床验证的基于pcr的检测方法进行的HPV检测在自我收集和临床收集的样本中具有相似的准确性。这些结果表明，HPV自采样可作为常规筛查的主要筛查方法。Elsevier Ltd.版权所有版权所有。
Background Human papillomavirus (HPV) testing on self-collected samples is a potential alternative to HPV testing on clinician-collected samples, but non-inferiority of its clinical accuracy remains to be assessed in the regular screening population. The IMPROVE study was done to evaluate the clinical accuracy of primary HPV testing on self-collected samples within an organised screening setting.Methods In this randomised, non-inferiority trial, women aged 29-61 years were invited to participate in the study as part of their regular screening invitation in the Netherlands. Women who provided informed consent were randomly allocated (1: 1, with a block size of ten stratified by age) to one of two groups: a self-sampling group, in which women were requested to collect their own cervicovaginal sample using an Evalyn Brush (Rovers Medical Devices BV, Oss, Netherlands); or a clinician-based sampling group, in which samples were collected by a general practitioner with a Cervex-Brush (Rovers Medical Devices BV). All samples were tested for HPV using the clinically validated GP5+/6+ PCR enzyme immunoassay (Labo Biomedical Products BV, Rijswijk, Netherlands). HPV-positive women in both groups were retested with the other collection method and triaged by cytology and repeat cytology in accordance with current Dutch screening guidelines. Primary endpoints were detection of cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) and grade 3 or worse (CIN3+). Non-inferiority of HPV testing on self-collected versus clinician-collected samples was evaluated against a margin of 90% for the relative sensitivity and 98% for the relative specificity. This study is registered at the Dutch Trial register (NTR5078) and has been completed.Findings Of the 187 473 women invited to participate, 8212 were randomly allocated to the self-sampling group and 8198 to the clinician-based sampling group. After exclusion of women who met the exclusion criteria or who did not return their sample, 7643 women were included in the self-sampling group and 6282 in the clinician-based sampling group. 569 (7.4%) self-collected samples and 451 (7.2%) clinician-collected samples tested positive for HPV (relative risk 1.04 [95% CI 0.92-1.17]). Median follow-up duration for HPV-positive women was 20 months (IQR 17-22). The CIN2+ sensitivity and specificity of HPV testing did not differ between self-sampling and clinician-based sampling (relative sensitivity 0.96 [0.90-1.03]; relative specificity 1.00 [0.99-1.01]). For the CIN3+ endpoint, relative sensitivity was 0.99 (0.91-1.08) and relative specificity was 1.00 (0.99-1.01).Interpretation HPV testing done with a clinically validated PCR-based assay had similar accuracy on self-collected and clinician-collected samples in terms of the detection of CIN2+ or CIN3+ lesions. These findings suggest that HPV self-sampling could be used as a primary screening method in routine screening. Copyright (C) 2019 Elsevier Ltd. All rights reserved.