Objectives To provide updated evidence about the risk of cervical intraepithelial neoplasia grade 3 or higher (CIN3+) and cervical cancer after a negative human papillomavirus (HPV) test in primary cervical screening, by age group and test assay. Design Observational study. Setting Real world data from the English HPV screening pilot’s first and second rounds (2013-16, follow-up to end of 2019). Participants 1 341 584 women. Interventions Cervical screening with HPV testing or liquid based cytological testing (cytology or smear tests). Women screened with cytology were referred to colposcopy after high grade cytological abnormalities or after borderline or low grade abnormalities combined with a positive HPV triage test. Women screened with HPV testing who were positive were referred at baseline if their cytology triage test showed at least borderline abnormalities or after a retest (early recall) at 12 and 24 months if they had persistent abnormalities. Main outcome measures Detection of CIN3+ and cervical cancer after a negative HPV test. Results For women younger than 50 years, second round detection of CIN3+ in this study was significantly lower after a negative HPV screen in the first round than after cytology testing (1.21/1000 v 4.52/1000 women screened, adjusted odds ratio 0.26, 95% confidence interval 0.23 to 0.30), as was the risk of interval cervical cancer (1.31/100 000 v 2.90/100 000 woman years, adjusted hazard ratio 0.44, 0.23 to 0.84). Risk of an incident CIN3+ detected at the second screening round in the pilot five years after a negative HPV test was even lower in women older than 50 years, than in three years in women younger than 50 years (0.57/1000 v 1.21/1000 women screened, adjusted odds ratio 0.46, 0.27 to 0.79). Women with negative HPV tests at early recall after a positive HPV screening test without cytological abnormalities had a higher detection rate of CIN3+ at the second routine recall than women who initially tested HPV negative (5.39/1000 v 1.21/1000 women screened, adjusted odds ratio 3.27, 95% confidence interval 2.21 to 4.84). Detection after a negative result on a clinically validated APTIMA mRNA HPV test was similar to that after clinically validated cobas and RealTime DNA tests (for CIN3+ at the second round 1.32/1000 v 1.14/1000 women screened, adjusted odds ratio 1.05, 0.73 to 1.50). Conclusions These data support an extension of the screening intervals, regardless of the test assay used: to five years after a negative HPV test in women aged 25-49 years, and even longer for women aged 50 years and older. The screening interval for HPV positive women who have negative HPV tests at early recall should be kept at three years. The data belong to the former Public Health England and the authors cannot provide access to the relevant datasets to third parties. Requests for data and pre-application advice should instead be made to Office for Data Release (ODR@phe.gov.uk).

中文翻译：

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通过初次人乳头瘤病毒检测延长宫颈筛查间隔：英国筛查试点数据的观察性研究


目的 提供关于初次宫颈筛查中人乳头瘤病毒 (HPV) 检测阴性后，按年龄组和检测分析划分的 3 级或以上宫颈上皮内瘤变 (CIN3+) 和宫颈癌风险的最新证据。设计观察性研究。设置英国 HPV 筛查试点第一轮和第二轮（2013-16 年，后续至 2019 年底）的真实世界数据。参与者 1 341 584 名女性。干预措施 通过 HPV 检测或液基细胞学检测（细胞学或涂片检测）进行宫颈筛查。经过细胞学筛查的女性在出现高度细胞学异常或边缘或低度异常并伴有 HPV 分类检测阳性后，被转诊至阴道镜检查。如果女性的细胞学分类测试显示至少有临界异常，则在基线时进行 HPV 检测筛查，结果呈阳性的女性将被转诊；如果她们持续存在异常，则在 12 个月和 24 个月时进行重新测试（早期召回）后转诊。主要结果指标 HPV 检测阴性后 CIN3+ 和宫颈癌的检测。结果 对于 50 岁以下的女性，本研究中第一轮 HPV 筛查阴性后第二轮 CIN3+ 检出率显着低于细胞学检测后（1.21/1000 例 vs 4.52/1000 例筛查女性，调整优势比 0.26，95%）置信区间 0.23 至 0.30），区间宫颈癌的风险也是如此（1.31/100 000 比 2.90/100 000 女性年，调整后的风险比 0.44、0.23 至 0.84）。 50 岁以上女性 HPV 检测呈阴性五年后，试点第二轮筛查中检测到 CIN3+ 事件的风险甚至低于 50 岁以下女性三年内的风险（0.57/1000 vs 1.21/1000）筛选，调整优势比 0.46、0.27 至 0.79）。 在没有细胞学异常的 HPV 筛查测试呈阳性后，在早期回忆中 HPV 测试呈阴性的女性在第二次常规回忆时的 CIN3+ 检出率高于最初测试 HPV 阴性的女性（5.39/1000 vs 1.21/1000 名筛查女性，调整优势比） 3.27，95% 置信区间 2.21 至 4.84）。经临床验证的 APTIMA mRNA HPV 检测呈阴性结果后的检测与经临床验证的 cobas 和 RealTime DNA 检测后的检测结果相似（第二轮 CIN3+ 1.32/1000 vs 1.14/1000 名接受筛查的女性，调整后的优势比为 1.05、0.73 至 1.50 ）。结论 这些数据支持延长筛查间隔，无论使用何种检测方法：25-49 岁女性 HPV 检测呈阴性后筛查间隔可延长至 5 年，50 岁及以上女性则更长。对于早期召回时 HPV 检测呈阴性的 HPV 阳性女性，筛查间隔应保持在三年。这些数据属于前英格兰公共卫生部门，作者无法向第三方提供相关数据集的访问权限。如需数据和预申请建议，应向数据发布办公室 (ODR@phe.gov.uk) 提出。