The Valgent4 protocol: Robust analytical and clinical validation of 11 HPV assays with genotyping on cervical samples collected in SurePath medium.
Open accessAbstract
BACKGROUND: The VALidation of HPV GENoyping Tests (VALGENT) is an international initiative designed to validate HPV assays with genotyping capability. The VALGENT4 protocol differs from previous VALGENT installments as the sample collection medium is SurePath, and exclusively includes samples from women ≥30 years of age which is concordant with the majority of HPV primary screening guidelines. Here we present the protocol for the fourth installment of the VALGENT framework. OBJECTIVES: In VALGENT4 11 HPV assays will be evaluated using two comparator assays based on PCR with the GP5+/6+ primers. STUDY DESIGN: Overall, the VALGENT4 panel consists of 1,297 routine samples comprised of 998 unselected, consecutive samples, of which 51 samples had abnormal cytology with 13 women diagnosed with ≥CIN2, and 299 consecutive samples enriched for ≥ASCUS cytology (100 ASCUS, 100 LSIL, 99 HSIL) with 106 ≥CIN2 upon follow up. Manipulated and DNA extracted panel samples were characterized with respect to human beta globin (HBB) and overall DNA content and composition to quality assess the panel prior to distribution to the collaborating sites. RESULT: The relative cellularity (mean CT value of HBB from the Onclarity assay) on the 1,297 LBC samples (CT=24.8) was compared with 293 un-manipulated routine cytology screening samples (CT=23.8). Furthermore, the DNA extracted panel samples was characterized using the Exome iPLEX pro assay, which reports amplifiable copies on individual samples as well as copies of five different base pair lengths. Here the data showed a slightly lower number of amplifiable DNA copies (ratio: 0.7, p=<0.01)) in the VALGENT4 panel samples compared to routine extracted cervical DNA samples CONCLUSION: The present manuscript details the manipulation, processing and quality assessment of samples used in VALGENT-4. This methodological document may be of value for future international projects of HPV test validation.
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Differences in detection technologies between the assays (Onclarity targeting E6/E7 versus Anyplex targeting L1, different amplicon lengths, and Onclarity's bulk grouping versus Anyplex's individual genotyping) might affect the concordance between the assays.
“Altogether, these differences in detection technologies might affect the concordance between the assays.”
From Comparison of Seegene Anyplex II HPV28 assay with BD Onclarity HPV assay for human papillomavirus genotyping (2022) · cites this paper as [36]
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredOnclarity has an amplification target range from 79 to 137 base pairs, whereas Anyplex has a target range of approximately 150 base pairs.
“Moreover, Onclarity has an amplification target range from 79 to 137 base pairs, whereas Anyplex has a target range of ~150 base pairs [36].”
From Comparison of Seegene Anyplex II HPV28 assay with BD Onclarity HPV assay for human papillomavirus genotyping (2022) · cites this paper as [36]
Onclarity targets the E6/E7 gene of HPV, whereas Anyplex targets the L1 gene.
“Although Onclarity targets the E6/E7 gene of HPV [14], Anyplex targets the L1 gene [36].”
From Comparison of Seegene Anyplex II HPV28 assay with BD Onclarity HPV assay for human papillomavirus genotyping (2022) · cites this paper as [36]
Table 1 lists both BD Onclarity and Seegene Anyplex assays and gives their amplicon lengths, but not the HPV genes they target. Sections 3.9.1 and 3.9.3 describe Onclarity testing without identifying an E6/E7 target. Searches for L1 and E6/E7 found no passage in our copy establishing the claimed targets. (LLM, conf=0.77)
Experimental — accuracy not yet measured
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Cites
Ronco, G., Dillner, J., Elfström, K. M., Tunesi, S., Snijders, P. J. F., Arbyn, M., Kitchener, H., Segnan, N., Gilham, C., Giorgi-Rossi, P., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(13)62218-7 · Cited by 1,810 · see citing works
Self-citationVALGENT: a protocol for clinical validation of human papillomavirus assays
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Self-citationArbyn, M., Xu, L., Verdoodt, F., Cuzick, J., Szarewski, A., Belinson, J. L., Wentzensen, N., Gage, J. C., & Khan, M. J. (2017) · Annals of Internal Medicine · doi:10.7326/m15-2735 · Cited by 68 · see citing works
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Self-citationCuschieri, K., Geraets, D., Cuzick, J., Cadman, L., Moore, C., Vanden Broeck, D., Padalko, E., Quint, W., & Arbyn, M. (2016) · Journal of Clinical Microbiology · doi:10.1128/jcm.00897-16 · Cited by 55 · see citing works
Self-citationAssessment of the Roche Linear Array HPV Genotyping Test within the VALGENT framework
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Kim, M., Kim, J., Park, N. J.-Y., & Park, J. Y. (2022) · PLOS ONE · doi:10.1371/journal.pone.0267836 · Cited by 5 · see citing works
“Moreover, Onclarity has an amplification target range from 79 to 137 base pairs, whereas Anyplex has a target range of ~150 base pairs [36].”
Background
- Authors
- Bonde, J., Ejegod, D. M., Cuschieri, K., Dillner, J., Heideman, D. A. M., Quint, W., Pavon Ribas, M. A., Padalko, E., Christiansen, I. K., Xu, L., & Arbyn, M.
- Affiliations
- Copenhagen University Hospital (DK)
- Edinburgh Royal Infirmary (GB)
- Karolinska University Hospital (SE)
- Cancer Center Amsterdam (NL)
- DDL Diagnostic Laboratory (NL)
- Ghent University Hospital (BE)
- Akershus University Hospital (NO)
- Sciensano (Belgium) (BE)
- Corresponding author
- Bonde, Jesper
- ORCID
- Venue
- Journal of Clinical Virology
- Publisher
- Elsevier BV
- Published
- 2018-11
- Volume
- 108
- Pages
- 64-71
- ISSN
- 1386-6532 (ISSN-L)
- OpenAlex
- W2890089733
- Cited by
- 44
- References
- 6
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 7
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Clinical Virology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- HPV vaccine manufacturer
- Hologic
- Cepheid
- Qiagen
- Becton-Dickinson
- Euroimmun
- SelfScreen
- LifeRiver
- Genomica
- Genefirst
- COHEAHR Network (603019)
- 7th Framework Programme of DG Research and Innovation, European Commission
- Becton
- Dickinson and Company
- Genomica SAU
- Agena Biotech Gmbh
- Zhanghai Biotech
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
- Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
- Keywords
- HPV genotyping, cervical samples, primary HPV testing, ASCUS, cervical intraepithelial neoplasia, sample quality assessment
- MeSH terms
- Adult, Aged, Uterine Cervical Dysplasia, Uterine Cervical Neoplasms, Cervix Uteri, DNA, Viral, Female, Genotype, Humans, Mass Screening, Middle Aged, Quality Control, Sensitivity and Specificity, Specimen Handling, Papillomaviridae, Papillomavirus Infections, Early Detection of Cancer, Young Adult, Genotyping Techniques
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