Evaluation of human papillomavirus testing in primary screening for cervical abnormalities - Comparison of sensitivity, specificity, and frequency of referral
Evaluation of human papillomavirus testing in primary screening for cervical abnormalities - Comparison of sensitivity, specificity, and frequency of referral
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DOI：
10.1001/jama.288.14.1749
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发表时间：
2002-10-09
影响因子：
120.7
通讯作者：
Koutsky, LA
中科院分区：
文献类型：
--
作者：
Kulasingam, SL;Hughes, JP;Koutsky, LA
背景 对接受巴氏涂片 (Pap) 涂片显示意义未明的非典型鳞状细胞 (ASCUS) 的女性进行人乳头瘤病毒 (HPV) DNA 检测具有临床用途。单独进行 HPV DNA 检测是否有助于初级筛查仍有待确定。 目的 确定 HPV DNA 检测检测宫颈上皮内瘤变 (CIN) 3 级或癌症（标准）的准确性。 设计、设置和参与者 1997 年 12 月至 2000 年 10 月期间，使用薄层巴氏涂片和宫颈抹片对 4075 名在华盛顿州计划生育诊所就诊的妇女进行了同时筛查。 通过基于聚合酶链式反应 (PCR) 的方法以及基于液体的 RNA-DNA 杂交捕获和信号放大测定（信号放大）进行 HPV DNA 检测。高危 HPV 类型呈阳性或巴氏涂片检查结果为 ASCUS 或更高的女性被视为筛查测试结果呈阳性，并被转诊进行阴道镜检查和活检。此外，筛查测试结果为阴性的女性随机样本被转介进行阴道镜检查。根据筛查和阴道镜检查的单独和组合薄层巴氏涂片、HPV PCR 和 HPV 信号放大测试结果，定义和评估了 7 种阴道镜检查分诊策略。主要结果测量 7 种分诊策略中每种策略检测 CIN 3 级或更高级别宫颈病变的敏感性和特异性。结果 CIN 3 或更高级别的估计患病率为 3.2%。薄层巴氏涂片（ASCUS 结果）识别 CIN 3 或更高级别女性的敏感性（95% 置信区间）仅为 61.3% (48.5%-70.9%)，而 PCR HPV 检测的敏感性为 88.2% (78.9%-93.8%)，信号放大的敏感性为 90.8% (83.1%-95.8%)。还观察到特异性差异：薄层巴氏涂片（结果大于或等于 ASCUS）为 82.4%（81.8%-83.1%），PCR 为 78.8%（77.9%-79.7%），信号放大为 72.6%（69.4%75.0%）。与所有患有 ASCUS 或更高级别的女性转诊进行阴道镜检查相比，对患有 ASCUS 的女性进行信号放大测试以及转诊结果呈阳性的女性的敏感性（分别为 61.3% 和 60.3%）大致相同，并且特异性更高（分别为 82.4% 和 88.9%）。需要两次就诊重复阳性 PCR 检测的策略的敏感性为 84.2% (75.3%-91.0%)，特异性为 86.2% (85.1%-87.3%)。与年轻女性相比，老年（大于或等于 30 岁）女性的所有检测都具有更高的特异性，但敏感性较低。结论 HPV 检测比薄层巴氏筛查具有更高的敏感性，但特异性较低。在某些情况下，特别是在筛查间隔较长或随意的情况下，HPV DNA 筛查可能是育龄妇女基于细胞学筛查的合理替代方案。
Context Human papillomavirus (HPV) DNA testing of women having Papanicolaou (Pap) smears showing atypical squamous cells of undetermined significance (ASCUS) has clinical usefulness. Whether HPV DNA testing alone is useful in primary screening remains to be determined.Objective To determine the accuracy of HPV DNA testing for detecting cervical intraepithelial neoplasia (CIN) grade 3 or cancer (the criterion standard).Design, Setting, and Participants Between December 1997 and October 2000, 4075 women who attended Planned Parenthood clinics in Washington State were screened simultaneously using thin-layer Pap and HPV DNA testing by a polymerase chain reaction (PCR)-based method and by a liquid-based RNA-DNA hybridization capture with signal amplification assay (signal amplification). Women who were positive for high-risk HPV types, or had Pap results of ASCUS or higher, were considered to have positive screening test results and were referred for colposcopy and biopsy. Additionally, a random sample of women with negative screening test results was referred for colposcopy. Based on individual and combined thin-layer Pap, HPV PCR, and HPV signal amplification test results from the screening and the colposcopy visits, 7 colposcopy triage strategies were defined and evaluated.Main Outcome Measure Sensitivity and specificity for detecting cervical lesions graded CIN 3 or higher for each of the 7 triage strategies.Results The estimated prevalence of CIN 3 or higher was 3.2%. The sensitivity (95% confidence interval) of thin-layer Pap (with a result of ASCUS) for identifying women with CIN 3 or higher was only 61.3% (48.5%-70.9%) compared with 88.2% (78.9%-93.8%) for HPV testing by PCR and 90.8% (83.1%-95.8%) by signal amplification. Differences in specificities were also observed: 82.4% (81.8%-83.1%) for thin-layer Pap (with a result of greater than or equal to ASCUS), 78.8% (77.9%-79.7%) for PCR, and 72.6% (69.4%75.0%) for signal amplification. Compared with referral for colposcopy of all women with ASCUS or higher, signal amplification testing of women with ASCUS and referral of those with a positive result was about as sensitive (61.3% vs 60.3%, respectively) and significantly more specific (82.4% vs 88.9%, respectively). The strategy requiring repeat positive PCR tests on 2 visits had a sensitivity of 84.2% (75.3%-91.0%) and a specificity of 86.2% (85.1%-87.3%). All tests were more specific and less sensitive in older (greater than or equal to30 years) vs younger women.Conclusions Testing for HPV has higher sensitivity but lower specificity than thin-layer Pap screening. In some settings, particularly where screening intervals are long or haphazard, screening for HPV DNA may be a reasonable alternative to cytology-based screening of reproductive-age women.