Lei Jiayao, Cuschieri Kate, Patel Hasit, Lawrence Alexandra, Deats Katie, Sasieni Peter, Lim Anita W W
Centre for Cancer Screening, Prevention, and Early Diagnosis, Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
PLoS Med. 2024 Dec 12;21(12):e1004494. doi: 10.1371/journal.pmed.1004494. eCollection 2024 Dec.
Human papillomavirus (HPV) testing of self-collected vaginal samples has potential to improve coverage of cervical screening programmes, but current guidelines mostly require those HPV positive on a self-sample to attend for routine screening.
A pragmatic modified stepped-wedge implementation feasibility trial was conducted at primary care practices in England. Individuals aged 25 to 64 years who were at least 6 months overdue for cervical screening could provide a self-collected sample. The primary outcomes included the monthly proportion of non-attenders screened, changes in coverage, and uptake within 90 days. Self-samples from 7,739 individuals were analysed using Roche Cobas 4800. Individuals with a positive self-sample were encouraged to attend clinical screening. In this post hoc study of the trial, we related the HPV type (HPV16, HPV18, or other high-risk type) and cycle threshold (Ct) value on the self-sample to the results of clinician-collected sample and cervical intraepithelial neoplasia grade 2 or worse (CIN2+). We wished to triage HPV-positive individuals to immediate colposcopy, clinician sampling, or 12-month recall depending on risk. A total of 1,001 women tested positive through self-samples, and 855 women who had both an HPV-positive self-sample and a subsequent clinician-sample were included in this study. Of these, 71 (8.3%) had CIN2+. Self-sample Ct values were highly predictive of HPV in the clinician sample. Combining HPV type and Ct value allowed stratification into 3 risk groups; 44/855 (5%) were high-risk of whom 43% (19/44, 95% confidence interval [29.7%, 57.8%]) had CIN2+. The majority (52.9%, 452/855) were low-risk, of whom 4% (18/452, 95% CI [2.5%, 6.2%]) had CIN2+. The main limitation of our study was the colposcopy assessment was restricted to individuals who had abnormal cytology after positive results of both self-sample and clinician-collected sample.
HPV type and Ct value on HPV-positive self-samples may be used for triage. The difference in the risk of CIN2+ in these groups appears sufficient to justify differential clinical management. A prospective study employing such triage to evaluate laboratory workflow, acceptability, and follow-up procedure and to optimise clinical performance seems warranted.
ISRCTN12759467.
对自行采集的阴道样本进行人乳头瘤病毒（HPV）检测有潜力提高宫颈癌筛查项目的覆盖率，但目前的指南大多要求自行采样HPV检测呈阳性者参加常规筛查。
在英格兰的基层医疗实践中进行了一项实用的改良阶梯式楔形实施可行性试验。年龄在25至64岁且宫颈癌筛查逾期至少6个月的个体可提供自行采集的样本。主要结局包括每月未参加筛查者的筛查比例、覆盖率变化以及90天内的接受率。使用罗氏Cobas 4800对7739名个体的自行采集样本进行分析。鼓励自行采样呈阳性的个体参加临床筛查。在该试验的这项事后研究中，我们将自行采集样本的HPV类型（HPV16、HPV18或其他高危型）和循环阈值（Ct）值与临床医生采集样本的结果以及宫颈上皮内瘤变2级或更严重病变（CIN2+）相关联。我们希望根据风险将HPV阳性个体分流至立即进行阴道镜检查、临床医生采样或12个月召回。共有1001名女性通过自行采集样本检测呈阳性，本研究纳入了855名自行采集样本HPV阳性且随后有临床医生采集样本的女性。其中，71名（8.3%）患有CIN2+。自行采集样本的Ct值对临床医生采集样本中的HPV具有高度预测性。结合HPV类型和Ct值可将其分为3个风险组；44/855（5%）为高危组，其中43%（19/44，95%置信区间[29.7%，57.8%]）患有CIN2+。大多数（52.9%，452/855）为低危组，其中4%（18/452，95%CI[2.5%，6.2%]）患有CIN2+。我们研究的主要局限性在于阴道镜检查评估仅限于自行采集样本和临床医生采集样本结果均为阳性后细胞学异常的个体。
HPV阳性自行采集样本的HPV类型和Ct值可用于分流。这些组中CIN2+风险的差异似乎足以证明进行差异化临床管理的合理性。开展一项前瞻性研究，采用这种分流方法来评估实验室工作流程、可接受性和随访程序，并优化临床表现似乎是有必要的。
ISRCTN12759467
