Department of Public Health, University of Copenhagen, Øster Farimagsgade 5, DK-1014 København K, Denmark.
BMJ. 2011 May 23;342:d2757. doi: 10.1136/bmj.d2757.
To determine the trade-off between the sensitivity and the specificity for high grade cervical intraepithelial neoplasia at hybrid capture 2 cut-off values above the standard ≥ 1 relative light units/cut-off level (rlu/co).
Systematic review.
PubMed.
Randomised controlled trials in primary cervical screening using hybrid capture 2 testing in the intervention arms. Articles published until August 2010 were included if the numbers of women with positive test results and with cervical intraepithelial neoplasia were stratified by hybrid capture 2 cut-off levels.
Women in the baseline screening rounds of the trials.
Hybrid capture 2 screening in the baseline round including the diagnostic follow-up as practised in the randomised controlled trials and as reported by hybrid capture 2 cut-off values.
Owing to heterogeneity in the trials, meta-analysis was not possible. Including cut-off values up to ≥ 10 rlu/co, 25 observation points were available for analysis. The relative sensitivity for cervical intraepithelial neoplasia grade III or higher at cut-off levels of ≥ 2, ≥ 4 or ≥ 5, and ≥ 10 rlu/co compared with a cut-off level of ≥ 1 rlu/co varied by trial, but at their lowest they were 0.97, 0.92, and 0.91, respectively. A similar pattern was observed for cervical intraepithelial neoplasia grade II or higher. The specificity would increase by at least 1%, 2%, and 3%, respectively, so that up to 24%, 39%, and 53%, of positive hybrid capture 2 test results not associated with high grade neoplasia could be avoided. Only two outliers existed to this general pattern.
Although the data were derived from the baseline screening rounds only, the decrease in the sensitivity for high grade cervical intraepithelial neoplasia using a hybrid capture 2 cut-off level between ≥ 2 rlu/co and ≥ 10 rlu/co seemed acceptable given the international recommendations for testing for human papillomavirus DNA in cervical screening, which require 90% or more sensitivity for cervical intraepithelial neoplasia grade II or higher compared with hybrid capture 2 at ≥ 1 rlu/co. The data suggest that the hybrid capture 2 cut-off level could be increased in primary screening; this seems reasonably safe and is significantly less burdensome for women.
确定杂交捕获 2 检测在标准≥1 相对光单位/临界值（rlu/co）以上的高等级宫颈上皮内瘤变的灵敏度和特异性之间的权衡。
系统评价。
PubMed。
使用杂交捕获 2 检测在干预臂中进行原发性宫颈筛查的随机对照试验。如果在杂交捕获 2 临界值分层的情况下，有阳性检测结果和宫颈上皮内瘤变的女性数量分层，则纳入直至 2010 年 8 月发表的文章。
试验基线筛查轮次的女性。
在基线筛查轮次中进行杂交捕获 2 筛查，包括随机对照试验中所采用的诊断随访以及杂交捕获 2 临界值报告的随访。
由于试验的异质性，无法进行荟萃分析。包括临界值高达≥10 rlu/co，有 25 个观察点可供分析。在临界值≥2、≥4 或≥5 和≥10 rlu/co 时，与临界值≥1 rlu/co 相比，宫颈上皮内瘤变≥III 级的相对灵敏度因试验而异，但最低值分别为 0.97、0.92 和 0.91。对于宫颈上皮内瘤变≥II 级也观察到类似的模式。特异性将至少提高 1%、2%和 3%，从而可以避免高达 24%、39%和 53%的与高级别肿瘤无关的阳性杂交捕获 2 检测结果。只有两个异常值与这一普遍模式不符。
尽管数据仅来自基线筛查轮次，但考虑到国际上对 HPV DNA 检测用于宫颈癌筛查的建议，即需要比杂交捕获 2 在≥1 rlu/co 时高 90%或更高的灵敏度来检测宫颈上皮内瘤变≥II 级，使用杂交捕获 2 在临界值≥2 rlu/co 与≥10 rlu/co 之间检测高级别宫颈上皮内瘤变时，灵敏度的降低似乎是可以接受的。数据表明，在初级筛查中可以增加杂交捕获 2 的临界值；这似乎是合理安全的，并且对女性的负担显著减轻。
