Clinical and Analytical Performance of the Onclarity HPV Assay Using the VALGENT Framework

Abstract

dAs the demand for human papillomavirus (HPV)-related cervical screening increases, emerging HPV tests must be evaluated robustly using well-annotated samples, such as those generated in the Validation of HPV Genotyping Tests (VALGENT) framework. Through VALGENT, we assessed the performance of the BD Onclarity HPV assay, which detects 14 high-risk (HR) types and resolves six individual types and three groups of types. Consecutive samples from a screening population (n ‫؍‬ 1,000), enriched with cytologically abnormal samples (n ‫؍‬ 300), that had been tested previously with the GP5؉/6؉ PCR enzyme immunoassay (EIA) and the GP5؉/6؉ PCR LMNX assay (Diassay) were tested with the Onclarity assay. Type-specific HPV prevalences were analyzed according to age and cytological result. The accuracy of the Onclarity assay for the detection of cervical intraepithelial neoplasia grade 2؉ (CIN2؉) and CIN3؉ was assessed relative to the GP5؉/6؉ EIA results by using noninferiority criteria. Overall agreement and type-specific agreement between the Onclarity assay and the GP5؉/6؉ LMNX assay were assessed. T he choice of tests for human papillomavirus (HPV) has expanded significantly in the past 5 years, consistent with increased evidence for the use of HPV testing for cervical disease management and epidemiological surveillance (1, 2). Comprehensive reviews have listed over 150 commercially available HPV tests (3). In general, HPV tests may be described as consensus assays, consensus assays with limited typing (often for HPV-16 and HPV-18), and extended genotyping tests (which offer typing beyond HPV-16/HPV-18). The first two types of tests tend to be more automated and thus more geared to high-throughput screening than extended genotyping tests, which provide the detailed data required for epidemiological work (4). Given the increased variety of HPV tests, it is important that their performance is assessed robustly, particularly if the results are to be used in the patient pathway.The Onclarity HPV assay provides consensus results via a highthroughput automated platform and also offers genotyping beyond HPV-16/HPV-18, with individual resolution of types 16, 18, 31, 45, 51, and 52 and identification of three groups of types: 33/58, 56/59/66, and 35/39/68. Initial work showed the test to be reproducible and clinically applicable in a primary cervical cancer screening setting (5). However, more data on performance, particularly at a type-specific level, is required with regard to clinical applications (6-8).Using a sample panel collated by the Validation of HPV Genotyping Tests (VALGENT) framework (9-12), the primary objective of this work was to determine the clinical performance of the Onclarity assay for primary cervical cancer screening. This was performed using international validation criteria based on the equivalency criteria described by Meijer et al. (13), with the GP5ϩ/6ϩ enzyme immunoassay (EIA) being used as the clinically validated comparator test. In addition, information on typespecific prevalence stratified by age and...

Performance of a Cartridge-Based Assay for Detection of Clinically Significant Human Papillomavirus (HPV) Infection: Lessons from VALGENT (Validation of HPV Genotyping Tests)

“…Indeed, aggregation of these data with those from the VALGENT-2 series allowed more precise assessment of the performance of the Xpert HPV in women older than 30, an important consideration given that many HPV-based primary screening protocols stipulate 30 as a minimum age for application. Consistent with previous work (9), the data also demonstrate the high prevalence of HR HPV in the United Kingdom, particularly in young women, emphasizing the need for appropriate triage strategies in an era of HPV primary screening (18).…”

“…Samples used for the present analysis constitute the VALGENT-2 panel. A detailed description of this panel has been published previously (9,10). In brief, archived samples were collated at the cytopathology laboratory at the Royal Infirmary of Edinburgh in Scotland, which is one of eight National Health Service (NHS) laboratories that serve the Scottish Cervical Screening program and processes around 70,000 samples per year.…”

Strategies for screening and early detection of anal cancers: A narrative and systematic review and meta‐analysis of cytology, HPV testing, and other biomarkers

“…74 Some of these assays have received regulatory approval for use in cervical cancer screening, but there are currently no US Food and Drug Administration-approved tests for anal cancer screening or surveillance. Large studies evaluating HPV DNA assays for cervical cancer screening have demonstrated that the performance of these tests is very similar, [75][76][77][78][79][80] allowing the pooling of data across these tests.…”

Triage of high-risk HPV positive women in cervical cancer screening

“…The Onclarity HPV test offers extended genotyping of types 16, 19, 31, 45, 51, and 52 and identifies an additional three groups of 33/58, 56/59/66, and 35/39/68. The clinical and analytical performance of this test was recently assessed according to the VALGENT framework concluding that this assay offers applications for clinical workstreams [56]. Also other techniques as the GP5+/6+-LMNX, MALDI-TOF, qPCR test, and PapilloCheck offer extended genotyping.…”