--- title: "The Meijer Criteria Explained: Why They Matter for Your HPV Assay" description: "Explore the Meijer criteria for HPV assay validation, including clinical sensitivity, specificity, reproducibility and their role in IVDR and WHO PQ." url: https://qbdgroup.com/en/blog/meijer-criteria-hpv-assay-validation-ivdr-who-pq type: "Blog post" language: en published: 2026-10-14 author: "Sara Peeters & Davy Vanden Broeck" category: "Clinical" publisher: "QbD Group" citation: "QbD Group, \"The Meijer Criteria Explained: Why They Matter for Your HPV Assay\", https://qbdgroup.com/en/blog/meijer-criteria-hpv-assay-validation-ivdr-who-pq" --- # The Meijer Criteria Explained: Why They Matter for Your HPV Assay > Explore the Meijer criteria for HPV assay validation, including clinical sensitivity, specificity, reproducibility and their role in IVDR and WHO PQ. If you are validating an HPV test for cervical cancer screening, one name is likely to come up: Meijer. The Meijer criteria provide a recognised scientific benchmark for comparing new HPV assays with clinically validated tests. But understanding what they measure, and what they do not, is essential when planning clinical performance evidence for the EU IVDR and WHO Prequalification (PQ).

In This Blog Post:

## Why HPV Tests Needed Their Own Clinical Benchmark As HPV testing began to replace cytology in cervical cancer screening, a central challenge emerged. PCR-based assays can detect HPV DNA with high analytical sensitivity, but many HPV infections are transient and do not progress to cervical disease. Detecting more infections is therefore not automatically the same as improving screening. An assay that identifies infections with little clinical relevance can lead to unnecessary follow-up, patient anxiety and additional pressure on healthcare systems.

The question for screening programmes is not simply whether a test detects HPV DNA. It is whether its performance is clinically appropriate for identifying women at risk of cervical precancer.

Long-term trials with disease endpoints can provide that evidence, but they are demanding. The Dutch POBASCAM trial, for example, included approximately 44,000 women followed over two screening rounds, five years apart. Repeating trials on that scale for every new assay would be highly impractical. A comparator-based framework offered a more feasible way to assess whether a new assay performs sufficiently well for cervical screening. ## How the Meijer Criteria Shaped HPV Assay Validation Meijer and colleagues proposed evaluating new HPV assays against a clinically validated comparator, rather than requiring every manufacturer to reproduce a large, long-term screening trial. The approach addresses three central dimensions of performance: **relative clinical sensitivity, relative clinical specificity and reproducibility**. ### Relative Clinical Sensitivity and Specificity For the detection of cervical intraepithelial neoplasia grade 2 or worse (CIN2+), the criteria specify that a new assay should demonstrate:

Meijer Criteria for CIN2+ Detection:

The relevant lower confidence bounds must also meet the specified thresholds. This matters because a point estimate alone does not describe the uncertainty surrounding the observed result. The criteria are relative to a validated comparator. They should not be mistaken for a general statement that every HPV test must show 90% absolute sensitivity or 98% absolute specificity. ### Reproducibility Within and Between Laboratories A screening assay also needs to deliver dependable results when testing is repeated or performed in different laboratories. The commonly cited reproducibility criterion is an **agreement lower confidence bound above 87%**, assessed using a defined sample set. This addresses both intra-laboratory and inter-laboratory reproducibility. Clinical performance and reproducibility answer different questions. An assay may compare favourably with a reference method in one study, but its routine use also depends on whether results can be reproduced reliably. ## Do the Meijer Criteria Specify a Fixed Study Sample Size? Study design and sample-size expectations in contemporary HPV assay evaluations may build on the original Meijer publication, but they should not all be attributed directly to the 2009 criteria. For example, some current protocols include at least 90 CIN2+ cases, of which at least 30 are CIN3+ cases. Those figures should be described as requirements of the specific evaluation protocol or applicable guidance, not as universal numbers laid down by Meijer in 2009. For manufacturers, the practical lesson is to identify the applicable protocol early and document why the selected population, comparator, endpoints and sample size are appropriate for the intended claim. ## Why the Meijer Criteria Still Matter for WHO Prequalification The Meijer criteria remain an important scientific benchmark for HPV nucleic acid tests intended for cervical cancer screening. WHO uses fulfilment of the Meijer 2009 criteria in an independent evaluation as the independent performance-evaluation component for HPV nucleic acid tests. That is an important component of the evidence strategy, but it is not the entire WHO PQ evidence package. Additional evidence may be needed to demonstrate that the assay is suitable for its intended users and settings, including the conditions in which screening programmes operate. A Meijer-based evaluation can therefore support WHO PQ without replacing the broader assessment of intended use and programme suitability. ## How Meijer-Based Evidence Fits Into IVDR Clinical Performance Under the EU In Vitro Diagnostic Medical Devices Regulation (IVDR), the Meijer criteria are not a standalone legal requirement. They can nevertheless provide a recognised scientific benchmark to support the state-of-the-art justification and clinical performance evaluation of an HPV screening assay. The manufacturer must still demonstrate that the device meets the applicable IVDR requirements for its intended purpose. That assessment extends beyond the comparator study alone and needs to address the relevant evidence and documentation for the particular device.

In other words, meeting a scientific benchmark is valuable evidence, but it does not automatically establish compliance with every regulatory requirement.

## One Scientific Foundation, Two Regulatory Pathways For manufacturers considering both the European market and WHO PQ, the Meijer criteria can provide a useful common starting point. An integrated strategy begins by mapping what both pathways expect before the study protocol is finalised. That makes it easier to identify evidence that can serve both purposes and gaps that require additional work.

Questions worth resolving early include:

The objective is not to assume that one study automatically satisfies both pathways. It is to build an evidence strategy that avoids unnecessary duplication while recognising the distinct requirements of each. ## The Takeaway: Use Meijer as a Benchmark, Not a Shortcut The Meijer criteria helped establish a practical scientific approach to HPV assay validation at a time when repeating large screening trials for every new test was unrealistic. They remain relevant today because they offer a recognised way to evaluate clinical performance and reproducibility against a validated comparator. For IVDR and WHO PQ, however, they are a foundation rather than a complete regulatory pathway. The evidence strategy must still account for the device's intended purpose, users, settings and the additional requirements of each framework. The strongest approach is to **map those requirements before drafting the protocol, not after the study has been completed.** ## Plan an HPV Clinical Performance Study for IVDR and WHO PQ QbD Group supports IVD manufacturers in translating scientific benchmarks and regulatory requirements into practical clinical performance strategies, including integrated approaches for IVDR and WHO Prequalification. Want to learn how to build a Meijer-based study for both pathways? [Watch our on-demand webinar](/en/webinars/ivdr-who-requirements-hpv-studies-on-demand) with Sara Peeters and Prof. Davy Vanden Broeck. --- Source: https://qbdgroup.com/en/blog/meijer-criteria-hpv-assay-validation-ivdr-who-pq — © QbD Group. Quote freely with attribution and a link back.