Arbyn Marc, Buntinx Frank, Van Ranst Marc, Paraskevaidis Evangelos, Martin-Hirsch Pierre, Dillner Joakim
European Network for Cervical Cancer Screening and Unit for Evaluation of Cancer Screening Programmes, Scientific Institute of Public Health, Brussels, Belgium.
J Natl Cancer Inst. 2004 Feb 18;96(4):280-93. doi: 10.1093/jnci/djh037.
The appropriate management of women with minor cytologic lesions in their cervix is unclear. We performed a meta-analysis to assess the accuracy of human papillomavirus (HPV) DNA testing as an alternative to repeat cytology in women who had equivocal results on a previous Pap smear.
Data were extracted from articles published between 1992 and 2002 that contained results of virologic and cytologic testing followed by colposcopically directed biopsy in women with an index smear showing atypical cells of undetermined significance (ASCUS). Fifteen studies were identified in which HPV triage and the histologic outcome (presence or absence of a cervical intraepithelial neoplasia of grade II or worse [CIN2+]) was documented. Nine, seven, and two studies also documented the accuracy of repeat cytology when the cutoff for abnormal cytology was set at a threshold of ASCUS or worse, low-grade squamous intraepithelial lesion (LSIL) or worse, or high-grade squamous intraepithelial lesion (HSIL) or worse, respectively. Random-effects models were used for pooling of accuracy parameters in case of interstudy heterogeneity. Differences in accuracy were assessed by pooling the ratio of the sensitivity (or specificity) of HPV testing to that of repeat cytology.
The sensitivity and specificity were 84.4% (95% confidence interval [CI] = 77.6% to 91.1%) and 72.9% (95% CI = 62.5% to 83.3%), respectively, for HPV testing overall and 94.8% (95% CI = 92.7% to 96.9%) and 67.3% (95% CI = 58.2% to 76.4%), respectively, for HPV testing in the eight studies that used the Hybrid Capture II assay. Sensitivity and specificity of repeat cytology at a threshold for abnormal cytology of ASCUS or worse was 81.8% (95% CI = 73.5% to 84.3%) and 57.6% (95% CI = 49.5% to 65.7%), respectively. Repeat cytology that used higher cytologic thresholds yielded substantially lower sensitivity but higher specificity than triage with the Hybrid Capture II assay. The ratio of the sensitivity of the Hybrid Capture II assay to that of repeat cytology at a threshold of ASCUS or worse pooled from the four studies that used both triage tests was 1.16 (95% CI = 1.04 to 1.29). The specificity ratio was not statistically different from unity.
The published literature indicates that the Hybrid Capture II assay has improved accuracy (higher sensitivity, similar specificity) than the repeat Pap smear using the threshold of ASCUS for an outcome of CIN2+ among women with equivocal cytologic results. The sensitivity of triage at higher cytologic cutoffs is poor.
对于宫颈存在轻微细胞学病变的女性，恰当的管理方式尚不清楚。我们进行了一项荟萃分析，以评估人乳头瘤病毒（HPV）DNA检测作为对既往巴氏涂片结果不明确的女性重复进行细胞学检查的替代方法的准确性。
从1992年至2002年发表的文章中提取数据，这些文章包含了对索引涂片显示意义不明确的非典型细胞（ASCUS）的女性进行病毒学和细胞学检测，随后进行阴道镜引导下活检的结果。共确定了15项研究，其中记录了HPV分流情况以及组织学结果（是否存在二级或更高级别的宫颈上皮内瘤变 [CIN2+]）。另外9项、7项和2项研究还分别记录了将异常细胞学的临界值设定为ASCUS或更差、低级别鳞状上皮内病变（LSIL）或更差、或高级别鳞状上皮内病变（HSIL）或更差时重复细胞学检查的准确性。在研究间存在异质性的情况下，使用随机效应模型汇总准确性参数。通过汇总HPV检测与重复细胞学检查的敏感性（或特异性）之比来评估准确性差异。
总体HPV检测的敏感性和特异性分别为84.4%（95%置信区间 [CI]=77.6%至91.1%）和72.9%（95%CI = 62.5%至83.3%），在使用杂交捕获II检测法的8项研究中，HPV检测的敏感性和特异性分别为94.8%（95%CI = 92.7%至96.9%）和67.3%（95%CI = 58.2%至76.4%）。以ASCUS或更差为异常细胞学临界值时，重复细胞学检查的敏感性和特异性分别为81.8%（95%CI = 73.5%至84.3%）和57.6%（95%CI = 49.5%至65.7%）。使用更高细胞学临界值的重复细胞学检查产生的敏感性显著低于杂交捕获II检测法进行的分流，但特异性更高。在使用两种分流检测法的4项研究中汇总得出，杂交捕获II检测法在ASCUS或更差临界值时的敏感性与重复细胞学检查的敏感性之比为1.16（95%CI = 1.04至1.29）。特异性之比与1无统计学差异。
已发表的文献表明，对于细胞学结果不明确的女性，在CIN2+的结局方面，杂交捕获II检测法比使用ASCUS临界值的重复巴氏涂片具有更高的准确性（更高的敏感性，相似的特异性）。在更高的细胞学临界值下进行分流的敏感性较差。
