Clinical performance of the HPV-Risk assay on cervical samples in SurePath medium using the VALGENT-4 panel

J Clin Virol. 2019 Dec;121:104201. doi: 10.1016/j.jcv.2019.104201. Epub 2019 Oct 12.

Abstract

Background: The VALidation of HPV GENoyping Tests (VALGENT) framework is designed for comparison and clinical validation of HPV assays.

Objectives: To evaluate the accuracy of the HPV-Risk assay within VALGENT-4, relative to clinically validated comparator HPV tests.

Study design: The VALGENT-4 panel comprises consecutive SurePath cervical samples from routine screening (n=998), of which 51 had abnormal cytology and 13 women had cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+), enriched with SurePath cervical samples from 297 women with abnormal cytology and 109 CIN2+. HPV-Risk assay was performed on DNA extracted panel samples (n=1,295), blinded to clinical data, cytology results, and results from other HPV assays evaluated in VALGENT-4. All assay results were reported to the central VALGENT coordination institute for data and statistical analysis. HPV prevalence was analysed and accuracy for detection of CIN grade 3 or worse (CIN3+) and CIN2+ were assessed relative to GP5+/6+-PCR-EIA and GP5+/6+-PCR-EIA-LMNX.

Results: The sensitivity of the HPV-Risk assay for detection of CIN3+ and CIN2+ was similar to that of GP5+/6+-PCR-EIA (relative sensitivity for CIN3+1.01; 95%CI: 0.97-1.06; pMcN=1.000, and for CIN2+1.01; 95%CI: 0.96-1.06; pMcN=1.000) at significantly higher specificity (relative specificity 1.04; 95%CI: 1.02-1.06; pMcN<0.001). The accuracy of the HPV-Risk assay for CIN3+ and CIN2+ was non-inferior compared to GP5+/6+-PCR- EIA and GP5+/6+-PCR-EIA-LMNX, with all p-values ≤0.002. HPV16/18 genotype agreement between HPV-Risk assay and GP5+/6+-PCR-LMNX was high.

Conclusions: The HPV-Risk assay demonstrated non-inferiority to clinically validated comparator assays on cervical samples in SurePath medium using the VALGENT-4 panel, and is therefore suitable for cervical cancer screening.

Keywords: Cervical cancer screening; Clinical validation; HPV-risk assay; Human papillomavirus; Liquid medium; Test accuracy.

MeSH terms

  • Adult
  • Cervical Intraepithelial Neoplasia / diagnosis
  • Cervical Intraepithelial Neoplasia / virology
  • Cervix Uteri / virology*
  • Culture Media / chemistry*
  • Early Detection of Cancer / instrumentation
  • Early Detection of Cancer / methods*
  • Female
  • Genotype
  • Human papillomavirus 16 / genetics
  • Human papillomavirus 18 / genetics
  • Humans
  • Middle Aged
  • Papillomaviridae / classification
  • Papillomaviridae / genetics*
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / virology
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / virology

Substances

  • Culture Media