采用 VALGENT4 框架下的 SurePath 介质中的宫颈样本对 Cobas 4800 HPV 检测进行临床验证。

Clinical validation of the Cobas 4800 HPV assay using cervical samples in SurePath medium under the VALGENT4 framework.

机构信息

Molecular Pathology Laboratory, Department of Pathology, Copenhagen University Hospital, Hvidovre, Kettegård Alle 30, 2650 Hvidovre, Denmark.

National HPV Reference Laboratory, Department of Microbiology and Infection Control, Akershus University Hospital, 1478 Lørenskog, Norway.

出版信息

J Clin Virol. 2020 Jul;128:104336. doi: 10.1016/j.jcv.2020.104336. Epub 2020 May 11.

DOI:10.1016/j.jcv.2020.104336

PMID:32446166

Abstract

BACKGROUND

The VALidation of HPV Genotyping Tests (VALGENT) framework is an international cooperation designed for comparison and clinical validation of HPV assays with genotyping capabilities.

OBJECTIVES

Here we addressed the accuracy of the Roche cobas 4800 HPV test using SurePath samples from the Danish cervical cancer screening program under the VALGENT framework.

MATERIAL AND METHODS

The VALGENT4 panel comprises 998 consecutive SurePath cervical samples from routine screening and 297 SurePath samples enriched for disease (100 ASC-US, 100 LSIL, 97 HSIL). The cobas HPV test is a real-time PCR assay which detects HPV16 and 18 individually and 12 other high-risk (hr) HPV genotypes in one bulk.

RESULTS

The clinical performance of the cobas test was assessed relative to that of the comparator assay GP5+/6 + PCR Enzyme ImmunoAssay (GP-EIA) by a non-inferiority test. The relative sensitivity for ≥ CIN2 was 1.00 (95% CI: 0.97-1.04) and relative specificity for the control group was 1.02 (95% CI: 1.01-1.04). The cobas test was found non-inferior to that of GP-EIA for both sensitivity and specificity (p-0.0006 and p < 0.0001, respectively). The type specific performance of the cobas test was evaluated using the GP5+/6 + PCR with Luminex genotyping (GP-LMNX) as comparator. The cobas test showed excellent to good concordance (Kappa: 0.70 to 0.90) with GP-LMNX for all three genotype groups in the overall VALGENT population but good to moderate concordance in the Screening population (kappa from 0.56 to 0.80).

CONCLUSIONS

The cobas HPV test demonstrated non-inferiority to the comparator assay on cervical SurePath screening samples using the VALGENT4 panel.

摘要

背景

VALidation of HPV Genotyping Tests（VALGENT）框架是一项国际合作，旨在比较和验证具有基因分型能力的 HPV 检测方法。

目的

本研究在 VALGENT 框架下，使用丹麦宫颈癌筛查项目中的 SurePath 样本，评估罗氏 cobas 4800 HPV 检测的准确性。

材料和方法

VALGENT4 面板包括 998 例连续的来自常规筛查的 SurePath 宫颈样本和 297 例疾病富集的 SurePath 样本（100 例 ASC-US、100 例 LSIL、97 例 HSIL）。 cobas HPV 检测是一种实时 PCR 检测方法，可单独检测 HPV16 和 18，也可同时检测 12 种其他高危（hr）HPV 基因型。

结果

采用非劣效性试验，将 cobas 检测与比较检测 GP5+/6 + PCR 酶免疫分析（GP-EIA）的临床性能进行比较。≥CIN2 的相对敏感性为 1.00（95%CI：0.97-1.04），对照组的相对特异性为 1.02（95%CI：1.01-1.04）。 cobas 检测在敏感性和特异性方面均优于 GP-EIA（p<0.0006 和 p<0.0001）。使用 GP5+/6 + PCR 与 Luminex 基因分型（GP-LMNX）作为比较检测，评估 cobas 检测的型特异性性能。 cobas 检测在 VALGENT 总体人群的所有三个基因型组中与 GP-LMNX 具有极好到极好的一致性（Kappa：0.70 至 0.90），但在筛查人群中的一致性为好到中度（kappa 从 0.56 到 0.80）。