Tranberg Mette, Van Keer Severien, Jensen Jørgen Skov, Nørgaard Pia, Gustafson Line Winther, Hammer Anne, Bor Pinar, Binderup Karen Omann, Blach Christina, Vorsters Alex
University Research Clinic for Cancer Screening, Dept. of Public Health Programmes, Randers Regional Hospital, Central Denmark Region, Skovlyvej 15, Randers, NO, 8930, Denmark.
Dept. of Pathology, Randers Regional Hospital, Central Denmark Region, Randers, Denmark.
BMC Med. 2025 Jun 2;23(1):327. doi: 10.1186/s12916-025-04149-0.
First-void urine (FVU) collection for high-risk human papillomavirus (hrHPV) testing has game-changing potential to improve cervical cancer prevention among under-screened women who remain unreached by clinician-based cervical cancer screening and vaginal self-sampling. Yet, the wide variation in the clinical accuracy of hrHPV testing in urine for detecting high-grade cervical intraepithelial neoplasia (CIN2 + /CIN3 +) across studies and clinical settings highlights the importance of local piloting and validation. This study determined the relative clinical accuracy of hrHPV testing in FVU versus clinician-collected cervical samples to detect CIN2 + /CIN3 + in a Danish referral population.
In a diagnostic test accuracy study, paired FVU (10 mL Colli-Pee device; index test) and cervical samples (Cervex Combi brush; comparator test) were obtained from 325 women aged 23-64 years (median age 36.0 years (IQR 29-46) who were either referred for colposcopy and biopsy taking or a cervical excision (reference test; available for all participants). Samples were tested using Allplex HR HPV DNA extended genotyping assay. Same absolute cut-off for hrHPV positivity applied for cervical samples was used for FVU. Of the 325 women, 145 (44.6%), 180 (55.4%), and 138 (42.5%) were diagnosed with < CIN2, CIN2 + , and CIN3 + , respectively.
Sensitivity to detect CIN2 + (ratio 0.97, 95% CI 0.92-1.02, p = 0.33) and CIN3 + (ratio 0.95, 95% CI 0.90-1.00, p = 0.09) using hrHPV testing in FVU samples was not significantly different to hrHPV testing in cervical samples, whereas specificity for < CIN2 (ratio 0.67, 95% CI 0.46-0.96, p = 0.04) was significantly lower in FVU than on cervical samples. Moderate to excellent hrHPV test agreements between paired samples were demonstrated (Cohen's kappa = 0.44 to 0.88).
This is the first study proving similar CIN2 + /CIN3 + sensitivity for FVU-hrHPV testing using the 10-mL Colli-Pee device and Allplex HR HPV assay compared to testing in cervical samples. From an implementation perspective, further research is needed to gather additional clinical accuracy and acceptability data on hrHPV testing of FVU-device collection in under-screened populations to support its broader integration into screening programmes.
Clinicaltrials.gov: NCT05065853.
用于高危型人乳头瘤病毒（hrHPV）检测的首次晨尿（FVU）采集，对于改善宫颈癌预防具有变革性潜力，尤其适用于那些未接受基于临床医生的宫颈癌筛查和阴道自我采样的筛查不足的女性。然而，在不同研究和临床环境中，尿液中hrHPV检测用于检测高级别宫颈上皮内瘤变（CIN2 + / CIN3 +）的临床准确性差异很大，这凸显了在当地进行试点和验证的重要性。本研究确定了在丹麦转诊人群中，FVU中hrHPV检测与临床医生采集的宫颈样本检测CIN2 + / CIN3 +的相对临床准确性。
在一项诊断试验准确性研究中，从325名年龄在23 - 64岁（中位年龄36.0岁（IQR 29 - 46））的女性中获取配对的FVU（10 mL Colli - Pee装置；指标试验）和宫颈样本（Cervex Combi刷；对照试验），这些女性要么被转诊进行阴道镜检查和活检，要么进行宫颈切除术（参考试验；所有参与者均可进行）。使用Allplex HR HPV DNA扩展基因分型检测对样本进行检测。宫颈样本中用于hrHPV阳性的相同绝对临界值用于FVU。在这325名女性中，分别有１４５名（44.6%）、180名（55.4%）和138名（42.5%）被诊断为＜CIN2、CIN2 +和CIN3 +。
使用FVU样本中的hrHPV检测来检测CIN2 +（比值0.97，95% CI 0.92 - 1.02，p = 0.33）和CIN3 +（比值0.95，95% CI 0.90 - 1.00，p = 0.09）的敏感性与宫颈样本中的hrHPV检测无显著差异，而FVU中＜CIN2的特异性（比值0.67，95% CI 0.46 - 0.96，p = 0.04）显著低于宫颈样本。配对样本之间显示出中度至高度的hrHPV检测一致性（Cohen's kappa = 0.44至0.88）。
这是第一项研究，证明使用10 mL Colli - Pee装置和Allplex HR HPV检测法进行FVU - hrHPV检测与宫颈样本检测相比，对CIN2 + / CIN3 +具有相似的敏感性。从实施角度来看，需要进一步研究以收集更多关于筛查不足人群中FVU装置采集的hrHPV检测的临床准确性和可接受性数据，以支持其更广泛地纳入筛查计划。
Clinicaltrials.gov：NCT05065853。
