Comparison of hybrid capture 2 High-Risk HPV results in the low positive range with cobas® HPV Test results from the ATHENA study

Abstract

Background: The increasing importance of high-risk human papillomavirus (hrHPV) testing in cervical cancer screening warrants evaluation of HPV DNA tests with an equivocal zone requiring retesting of samples in the low positive range.

Objectives: To compare the results of the digene hc2 High Risk HPV DNA Test (hc2), which has a manufacturer's recommended retesting zone with the cobas HPV Test, a real-time polymerase chain reaction amplification test without an equivocal range.

Study design: A retrospective subanalysis of the ATHENA study comparing results for hc2 High Risk HPV DNA Test and the cobas HPV Test using the LINEAR ARRAY HPV Genotyping Test (LA) and Sanger sequencing as comparators was performed. The ability of each test to detect high-grade cervical disease in the equivocal range was also evaluated.

Results: 5.2% of samples fell within the equivocal zone (RLU/CO 1.0-2.5) and required retesting with the hc2 High Risk HPV DNA Test. In this low-positive range the cobas HPV Test showed better positive percent agreement (PPA) than hc2 High Risk HPV DNA Test for LA and sequencing (84.2% vs.70.9% and 92.1% vs.82.5%, respectively). hc2 High Risk HPV DNA Test and the cobas HPV Test demonstrated comparable sensitivity for detection of high-grade disease in the equivocal range. In the low cobas HPV Test range (cycle threshold [Ct] 40-35), the cobas HPV test again demonstrated a better PPA than hc2 High Risk HPV DNA Test with LA and sequencing as comparators and more high-grade disease was detected by the cobas HPV Test than hc2 High Risk HPV DNA Test.

Conclusion: The cobas HPV Test demonstrates reliable performance in the hc2 High Risk HPV DNA Test equivocal zone, thus supporting it as an option for HPV testing that avoids the need for retesting.

Keywords: ASCCP; ASCUS; ATHENA; American Society for Colposcopy and Cervical Pathology; CIN; Cut off; HC2; HPV; HPV DNA tests; LA; Linear Array HPV Genotyping Test; Low positive range; NILM; NPA; OPA; PCR; PPA; Qiagen Hybrid Capture 2 HPV test; RLU; atypical squamous cells of undetermined significance; cervical intraepithelial neoplasia; cutoff; high-risk human papillomavirus; hrHPV; negative for intraepithelial lesions or malignancies; negative percent agreement; overall percent agreement; polymerase chain reaction; positive percent agreement; relative light unit.