BACKGROUND Clinical trials in the research setting have demonstrated that primary human papillomavirus (HPV)-based screening results in greater protection against cervical cancer compared with cytology, but evidence from real-life implementation was missing. To evaluate the effectiveness of HPV-based cervical screening within a real-life screening program, the organized, population-based cervical screening program in the capital region of Sweden offered either HPV- or cytology-based screening in a randomized manner through a randomized healthcare policy (RHP). METHODS AND FINDINGS A total of 395,725 women aged 30 to 64 years that were invited for their routine cervical screening visit were randomized without blinding to either cytology-based screening with HPV triage (n = 183,309) or HPV-based screening, with cytology triage (n = 212,416 women) between September 1, 2014 and September 30, 2016 and follow-up through June 30, 2017. The main outcome was non-inferior detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+). Secondary outcomes included superiority in CIN2+ detection, screening attendance, and referral to histology. In total, 120,240 had a cervical screening sample on record in the study period in the HPV arm and 99,340 in the cytology arm and were followed for the outcomes of interest. In per-protocol (PP) analyses, the detection rate of CIN2+ was 1.03% (95% confidence interval (CI) 0.98 to 1.10) in the HPV arm and 0.93% (0.87 to 0.99) in the cytology arm (p for non-inferiority <0.0001; odds ratio (OR) 1.11 (95% CI 1.02 to 1.22)). There were 46 cervical cancers detected in the HPV arm (0.04% (0.03 to 0.06)) and 48 cancers detected in the cytology arm (0.05% (0.04 to 0.07)) (p for non-inferiority <0.0001; OR 0.79 (0.53 to 1.18)). Intention-to-screen (ITS) analyses found few differences. In the HPV arm, there was a modestly increased attendance after new invitations (68.56% (68.31 to 68.80) vs. 67.71% (67.43 to 67.98); OR 1.02 (1.00 to 1.03)) and increased rate of referral with completed biopsy (3.89% (3.79 to 4.00) vs. 3.53% (3.42 to 3.65); OR 1.10 (1.05 to 1.15)). The main limitations of this analysis are that only the baseline results are presented, and there was an imbalance in invitations between the study arms. CONCLUSIONS In this study, we observed that a real-life RHP of primary HPV-based screening was acceptable and effective when evaluated against cytology-based screening, as indicated by comparable participation, referral, and detection rates. TRIAL REGISTRATION ClinicalTrials.gov NCT01511328.

中文翻译：

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有组织的基于原发性人乳头瘤病毒的宫颈筛查：一项随机医疗政策试验。

背景 研究环境中的临床试验表明，与细胞学相比，基于原发性人乳头瘤病毒 (HPV) 的筛查可以更好地预防宫颈癌，但缺少来自现实生活中的实施证据。为了在现实生活中的筛查计划中评估基于 HPV 的宫颈筛查的有效性，瑞典首都地区有组织的基于人群的宫颈筛查计划通过随机医疗保健以随机方式提供基于 HPV 或细胞学的筛查政策 (RHP)。方法和结果 共有 395,725 名年龄在 30 至 64 岁的受邀进行常规宫颈筛查的女性随机随机分组进行基于细胞学筛查的 HPV 分诊（n = 183,309）或基于 HPV 的筛查和细胞学分诊（ n = 212, 416 名女性）在 2014 年 9 月 1 日至 2016 年 9 月 30 日期间以及随访至 2017 年 6 月 30 日。主要结果是宫颈上皮内瘤变 2 级或更差（CIN2+）的非劣检出率。次要结果包括在 CIN2+ 检测、筛查出勤率和转诊到组织学方面的优势。在研究期间，HPV 组共有 120,240 人记录了宫颈筛查样本，细胞学组中有 99,340 人记录了宫颈筛查样本，并对感兴趣的结果进行了随访。在符合方案 (PP) 分析中，HPV 组的 CIN2+ 检出率为 1.03%（95% 置信区间 (CI) 0.98 至 1.10），细胞学组的 CIN2+ 检出率为 0.93%（0.87 至 0.99）（非 p自卑 <0.0001；优势比 (OR) 1.11（95% CI 1.02 至 1.22））。在 HPV 组中检测到 46 例宫颈癌（0.04%（0.03 至 0. 06)) 和在细胞学组中检测到的 48 种癌症（0.05%（0.04 至 0.07））（非劣效性 p <0.0001；OR 0.79（0.53 至 1.18））。意向筛选 (ITS) 分析发现差异很小。在 HPV 组中，新邀请后的出席率略有增加（68.56%（68.31 至 68.80）与 67.71%（67.43 至 67.98）；OR 1.02（1.00 至 1.03））和完成活检的转诊率增加（3.89） %（3.79 至 4.00）与 3.53%（3.42 至 3.65）；或 1.10（1.05 至 1.15））。该分析的主要局限性在于仅提供了基线结果，并且研究组之间的邀请不平衡。结论 在本研究中，我们观察到，与基于细胞学的筛查相比，基于 HPV 的初级筛查的真实 RHP 是可接受和有效的，如可比参与、转诊、和检出率。试验注册 ClinicalTrials.gov NCT01511328。