Cancer Centre Amsterdam, Department of Pathology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.
Department of Obstetrics and Gynaecology, Radboud University Medical Centre, Nijmegen, Netherlands.
Lancet Oncol. 2019 Feb;20(2):229-238. doi: 10.1016/S1470-2045(18)30763-0. Epub 2019 Jan 15.
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.
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.
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).
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.
Ministry of Health, Welfare, and Sport (Netherlands), and the European Commission.
人乳头瘤病毒（HPV）自我采集样本检测可能是临床医生采集样本检测的替代方法，但在常规筛查人群中，其临床准确性的非劣效性仍有待评估。IMPROVE 研究旨在评估在有组织的筛查环境中，自我采集样本进行原发性 HPV 检测的临床准确性。
在这项随机、非劣效性试验中，邀请 29-61 岁的女性参加该研究，作为其在荷兰常规筛查邀请的一部分。提供知情同意的女性被随机分配（1:1，按年龄分层的 10 个区组大小）到两组之一：自我采样组，要求女性使用 Evalyn 刷子（Rovers Medical Devices BV，荷兰 Oss）自行采集宫颈阴道样本；或临床医生采样组，由全科医生使用 Cervex-Brush（Rovers Medical Devices BV）采集样本。所有样本均采用经过临床验证的 GP5+/6+PCR 酶免疫测定法（Labo Biomedical Products BV，荷兰 Rijswijk）进行 HPV 检测。两组中 HPV 阳性的女性均使用另一种采集方法进行重复检测，并根据当前荷兰筛查指南进行细胞学和重复细胞学分类。主要终点是检测到宫颈上皮内瘤变（CIN）2 级或更高级别（CIN2+）和 3 级或更高级别（CIN3+）。HPV 自我采集样本与临床医生采集样本的检测相对敏感性的 90%和相对特异性的 98%的差值评估为非劣效性。该研究在荷兰试验注册处（NTR5078）注册，并已完成。
在 187473 名受邀参加的女性中，8212 名被随机分配到自我采样组，8198 名被分配到临床医生采样组。排除符合排除标准或未返回样本的女性后，7643 名女性被纳入自我采样组，6282 名女性被纳入临床医生采样组。569 份（7.4%）自我采集样本和 451 份（7.2%）临床医生采集样本 HPV 检测阳性（相对风险 1.04[95%CI 0.92-1.17]）。HPV 阳性女性的中位随访时间为 20 个月（IQR 17-22）。HPV 检测在自我采样和临床医生采样组中 CIN2+的敏感性和特异性没有差异（相对敏感性 0.96[0.90-1.03]；相对特异性 1.00[0.99-1.01]）。对于 CIN3+终点，相对敏感性为 0.99（0.91-1.08），相对特异性为 1.00（0.99-1.01）。
使用经过临床验证的基于 PCR 的 HPV 检测方法，在检测 CIN2+或 CIN3+病变方面，自我采集样本和临床医生采集样本的准确性相似。这些发现表明，HPV 自我采样可作为常规筛查中的一种主要筛查方法。
荷兰卫生、福利和体育部和欧盟委员会。
