Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial
Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial
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DOI：
10.1136/bmj.g130
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发表时间：
2014-01-16
影响因子：
105.7
通讯作者：
Dillner, Joakim
中科院分区：
文献类型：
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作者：
Elfstrom, K. Miriam;Smelov, Vitaly;Dillner, Joakim
目的评估人乳头瘤病毒（HPV）筛查敏感性的增加是否可能代表过度诊断，并比较HPV筛查和细胞学筛查对宫颈上皮内瘤变2级或更严重（CIN 2+）的长期保护作用。在Swedescreen进行的HPV初筛随机对照试验中，参与者12 527参加有组织的筛查的32-38岁的妇女被登记，并被随机分配到HPV和细胞学双重检测（干预组，n =6257）或仅进行细胞学检测，样品被冷冻用于将来的HPV检测（对照组，n=6270）。纵向测试的特点，计算细胞学，HPV检测，细胞学和HPV检测相结合，调整censoring.Results增加检测CIN 2+在干预臂随着时间的推移而下降。6年后，两组CIN 3+的累积发生率相似，11年后，两组CIN 2+的累积发生率相似。对照组3年时细胞学检查对CIN 2+的纵向敏感性与干预组5年随访时HPV检测的敏感性相似：85.94%（95%置信区间76.85%至91.84%）vs86.40%（79.21%至91.37%）。5年后HPV筛查CIN 3+的敏感性为89.34 3年后细胞学检查阳性率为92.02%结论在长期随访中，HPV筛查和细胞学检查的CIN 2+累积发生率相同，提示HPV筛查对CIN 2+的敏感性增加反映了早期检测而不是过度诊断。在HPV筛查中检测为阴性的妇女中CIN 3+的长期风险较低，支持这些妇女的筛查间隔为5年。
Objectives To assess whether the increased sensitivity of screening for human papillomavirus (HPV) may represent overdiagnosis and to compare the long term duration of protective effect against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV based and cytology based screening.Design 13 year follow-up of the Swedescreen randomised controlled trial of primary HPV screening.Setting Organised cervical screening programme in Sweden.Participants 12 527 women aged 32-38 attending organised screening were enrolled and randomised to HPV and cytology double testing (intervention arm, n=6257) or to cytology only, with samples frozen for future HPV testing (control arm, n=6270).Main outcome measures Cumulative incidence of CIN2+ and CIN3+ (Kaplan Meier curves). Longitudinal test characteristics were calculated for cytology only, HPV testing only, and cytology and HPV testing combined, adjusting for censoring.Results The increased detection of CIN2+ in the intervention arm decreased over time. After six years, the cumulative incidence of CIN3+ was similar in both trial arms, and after 11 years the cumulative incidence of CIN2+ became similar in both arms. The longitudinal sensitivity of cytology for CIN2+ in the control arm at three years was similar to the sensitivity of HPV testing in the intervention arm at five years of follow-up: 85.94% (95% confidence interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV screening for CIN3+ after five years was 89.34% (80.10% to 94.58%) and for cytology after three years was 92.02% (80.59% to 96.97%).Conclusions Over long term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening and for cytology, implying that the increased sensitivity of HPV screening for CIN2+ reflects earlier detection rather than overdiagnosis. The low long term risks of CIN3+ among women who tested negative in HPV screening, support screening intervals of five years for such women.