Unit of Cancer Epidemiology, Belgian Cancer Centre, Scientific Institute of Public Health, Brussels, Belgium; Department of Human Structure and Repair, Faculty of Medicine and Health Sciences, University Ghent, Ghent, Belgium.
Haute Autorité de Santé, Saint Denis, France.
Clin Microbiol Infect. 2021 Aug;27(8):1083-1095. doi: 10.1016/j.cmi.2021.04.031. Epub 2021 May 8.
Only clinically validated HPV assays can be accepted in cervical cancer screening.
To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009).
PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014 to August 2020.
HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer; CIN2+).
Women participating in cervical cancer screening.
Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome (<CIN2, CIN2+). Comparator HPV assays were HC2, GP5+/6+ PCR-EIA, recommended in validation guidelines, or tests with consistent previous validations.
Assessment of relative clinical accuracy (including non-inferiority statistics index vs comparator assay) and test reproducibility in individual studies; random effects meta-analyses of the relative clinical sensitivity and specificity of index vs comparator tests.
Seven hrHPV DNA tests consistently fulfilled all validation criteria in multiple studies using predefined test positivity cut-offs (Abbott RealTime High Risk HPV, Anyplex II HPV HR Detection, BD Onclarity HPV Assay, Cobas 4800 HPV Test, HPV-Risk Assay, PapilloCheck HPV-Screening Test and Xpert HPV). Another assay (Alinity m HR HPV Assay) was fully validated in one validation study. The newer Cobas 6800 HPV Test, was validated in two studies against Cobas 4800. Other tests partially fulfilled the international validation criteria (Cervista HPV HR Test, EUROArray HPV, Hybribio's 14 High-Risk HPV, LMNX Genotyping Kit GP HPV, MALDI-TOF, RIATOL qPCR and a number of other in-house developed assays) since the non-inferior accuracy was reached after a posteriori cut-off optimization, inconsistent accuracy findings in different studies, and/or insufficient reproducibility assessment. The APTIMA HPV Assay targeting E6/E7 mRNA of hrHPV was fully validated in one formal validation study and showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies. However, the current international validation criteria relate to DNA assays. The additional requirement for longitudinal performance data required for non-DNA based HPV assays was not assessed in this review.
Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens.
只有经过临床验证的 HPV 检测方法才能用于宫颈癌筛查。
更新符合 2009 年国际验证标准（Meijer-2009）的高危型 HPV 检测方法列表。
PubMed/Medline、Embase、Scopus，以及选定研究的参考文献；发表于 2014 年 1 月至 2020 年 8 月。
HPV 检测验证研究和初级筛查研究，涉及使用索引 HPV 检测和比较 HPV 检测，并报告疾病结局（组织学证实的宫颈前癌；CIN2+）。
参与宫颈癌筛查的女性。
对临床医生采集的宫颈标本进行索引和比较 HPV 检测，并评估疾病结局（<CIN2、CIN2+）。比较 HPV 检测方法为 HC2、GP5+/6+PCR-EIA，为验证指南推荐方法，或与之前验证一致的检测方法。
评估个体研究中相对临床准确性（包括非劣效性统计指数与比较检测方法）和检测可重复性；使用索引与比较检测方法的相对临床敏感性和特异性的随机效应荟萃分析。
七种 hrHPV DNA 检测方法在使用预设检测阳性界限的多项研究中一致满足所有验证标准（Abbott RealTime High Risk HPV、Anyplex II HPV HR Detection、BD Onclarity HPV Assay、Cobas 4800 HPV Test、HPV-Risk Assay、PapilloCheck HPV-Screening Test 和 Xpert HPV）。另一种检测方法（Alinity m HR HPV Assay）在一项验证研究中得到充分验证。更新的 Cobas 6800 HPV 检测在两项研究中与 Cobas 4800 进行了验证。其他检测方法（Cervista HPV HR Test、EUROArray HPV、Hybribio's 14 High-Risk HPV、LMNX Genotyping Kit GP HPV、MALDI-TOF、RIATOL qPCR 和许多其他内部开发的检测方法）部分满足国际验证标准，因为在使用后验优化的截止值后，其非劣效性准确性得到了验证，在不同研究中出现了不一致的准确性结果，和/或缺乏充分的可重复性评估。针对高危型 HPV 的 E6/E7 mRNA 的 APTIMA HPV 检测方法在一项正式验证研究中得到充分验证，在七项筛查研究中，该方法的总体敏感性略低于标准比较检测方法，但特异性更高。然而，目前的国际验证标准与 DNA 检测方法相关。本综述未评估基于非 DNA 的 HPV 检测方法所需的纵向性能数据的额外要求。
十一种 hrHPV DNA 检测方法符合使用临床医生采集的标本进行宫颈癌筛查的所有要求。
