Am J Obstet Gynecol. 2023 Oct 6:S0002-9378(23)00730-5. doi: 10.1016/j.ajog.2023.09.100. Online ahead of print.
ABSTRACT
BACKGROUND: The US Food and Drug Administration (FDA) supports innovations to facilitate new indications for high-risk human papillomavirus (HPV) testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity HPV assay (Becton, Dickinson and Company; BD Life Sciences Integrated Diagnostic Solutions; Sparks, MD, USA). The performance of this index test was compared to a predicate test, the cobas HPV assay (Roche Diagnostics; Indianapolis, IN, USA). Both HPV assays are based on real-time polymerase chain reaction (PCR) platforms that detect the presence of 14 high-risk HPV genotypes. The predicate assay reports HPV16 and 18 as individual results and the other 12 HPV genotypes as one pooled result. The index assay reports nine, independent results (HPV 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, 56/59/66). The index and predicate assays are both FDA-approved for cervical cancer screening but at the time that this study was initiated, the index HPV assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc.; San Diego, CA, USA) liquid-based cytology (LBC) media.
OBJECTIVES: The performance of the index HPV assay was compared to the predicate HPV assay for detection of cervical intraepithelial neoplasia grades 2 or 3 or worse (≥CIN2 or ≥CIN3) using PreservCyt LBC specimens collected from women ages 21-65 years. The ability of the index test’s extended genotyping to stratify ≥CIN2 or ≥CIN3 risks, using these specimens, was also evaluated.
STUDY DESIGN: The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A random subset of PreservCyt specimens from 4,820 of these women was selected for paired testing by the index and predicate HPV assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals (95% CI) to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to five-years follow-up, was estimated for the index assay using Kaplan-Meier methods.
RESULTS: Five-year cumulative ≥CIN3 detection was 5.6% and 4.6% for the index and predicate assay, respectively (difference=1.0% [.5% to 1.5%]). The ≥CIN3 positivity rate within <1-year for the index and predicate assay was 95.3% and 94.5%, respectively (ratio=1.01 [.98 to 1.06]). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at five-years. Among cases of ≥CIN3, positive agreement between the index and predicate assay for HPV16 and HPV18, was 100% (95%CI=95.0% to 100%), and 90.9% (95%CI=62.3% to 98.4%), respectively. HPV16 carried the highest ≥CIN2/3 risk, followed by HPV18/31/33/58/52/45, and then HPV35/56/59/51/56/59/66.
CONCLUSIONS: The index and predicate HPV assays demonstrated equivalent performance, and extended HPV genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt.
PMID:37806613 | DOI:10.1016/j.ajog.2023.09.100
