Clinical Validation of the BD Onclarity? HPV Assay Using a Non-Inferiority Test

Ejegod, Ditte Møller

doi:10.4172/2161-0703.s3-003

Cited by 15 publications

(34 citation statements)

References 20 publications

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“…In a multicenter U.S. study of the Onclarity assay using 541 archived samples, Wright and colleagues (24) reported the sensitivity and specificity of the assay for CIN2ϩ as 90.4% (95% CI, 83 to 95%) and 76.9% (95% CI, 73 to 81%), respectively, which are lower than the values reported in the present study, i.e., 96.1% (95% CI, 94.8 to 97.4%) and 89.1% (95% CI, 87.0 to 91.2%), respectively, and also lower than those reported by Ejegod et al (5). Again, the different populations must be considered; the U.S. study involved a younger population and histological "adjudication" by a review panel of pathologists, whereas, in the study by Ejegod et al (5) and the present study, the histological results were those derived from routine practice and were not reviewed.…”

Section: Discussioncontrasting

confidence: 56%

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

et al. 2015

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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...

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Section: Discussioncontrasting

confidence: 56%

“…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)(7)(8).…”

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

et al. 2015

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“…The Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) assay (2-4) and GP5ϩ/6ϩ PCR-based enzyme immunoassay (EIA) kit HPV GP HR (EIA; Diassay, Rijswijk, the Netherlands) (5-9) were the first HPV tests to be clinically validated for primary screening on the basis of longitudinal results from large screening studies (10). Testing for high-risk HPV (hrHPV) nucleic acids is also useful for triage of women with equivocal or mildly abnormal cytology for colposcopy and as a test of cure of treatment (10).Several novel HPV tests have been fully or partially validated by showing noninferiority to HC2 or EIA and high reproducibility (11), as has been extensively reviewed by Arbyn et al (10) and reported in additional studies (12)(13)(14). These tests usually detect around 14 hrHPVs in aggregate, but some provide concurrent (partial) genotype-specific information.…”

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confidence: 99%

“…Several novel HPV tests have been fully or partially validated by showing noninferiority to HC2 or EIA and high reproducibility (11), as has been extensively reviewed by Arbyn et al (10) and reported in additional studies (12)(13)(14). These tests usually detect around 14 hrHPVs in aggregate, but some provide concurrent (partial) genotype-specific information.…”

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confidence: 99%

Clinical Evaluation of a GP5+/6+-Based Luminex Assay Having Full High-Risk Human Papillomavirus Genotyping Capability and an Internal Control

et al. 2014

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The LMNX genotyping kit HPV GP (LMNX) is based on the clinically validated GP5؉/6؉ PCR, with a genotyping readout as an alternative for the more established enzyme immunoassay (EIA) detection of 14 targeted high-risk human papillomavirus (HPV) types. LMNX is additionally provided with an internal control probe. Here, we present an analysis of the clinical performance of the LMNX using a sample panel and infrastructure provided by the international VALGENT (Validation of Genotyping Tests) project. This panel consisted of cervical specimens from approximately 1,000 women attending routine screening, "enriched" with 300 women with abnormal cytology. Cases were defined as women classified with cervical intraepithelial neoplasia (CIN) grade 2؉ (CIN2؉) (n ‫؍‬ 102) or CIN3؉ (n ‫؍‬ 55) within the previous 18 months. Controls were women who had normal cytology results over two subsequent screening rounds at a 3-year interval (n ‫؍‬ 746). The GP5؉/6؉-PCR EIA (EIA) was used as a comparator assay and showed sensitivities of 94.1% and 98.2% for CIN2؉ and CIN3؉, respectively, with a clinical specificity of 92.4% among women aged >30 years. The LMNX demonstrated clinical sensitivities of 96.1% for CIN2؉ and of 98.2% for CIN3؉ and a clinical specificity of 92.6% for women aged >30 years. The LMNX and EIA were in high agreement (Cohen's kappa ‫؍‬ 0.969) for the detection of 14 hrHPVs in aggregate, and no significant difference was observed (McNemar's P ‫؍‬ 0.629). The LMNX internal control detected 0.6% inadequate specimens. Based on our study results, we consider the LMNX, similarly to the EIA, useful for HPV-based cervical cancer screening.H uman papillomavirus (HPV) tests that have been validated for use in a clinical setting usually target 13 or 14 genotypes. These HPVs have been classified by the International Agency for Research on Cancer (IARC) as carcinogenic, i.e., HPV16, HPV18, HPV31, HPV33, HPV35, HPV39, HPV45, HPV51, HPV52, HPV56, HPV58, and HPV59 (class 1), probably carcinogenic, i.e., HPV68 (class 2A), or possibly carcinogenic, i.e., HPV66 (class 2B) (1). The Hybrid Capture 2 (HC2; Qiagen, Hilden, Germany) assay (2-4) and GP5ϩ/6ϩ PCR-based enzyme immunoassay (EIA) kit HPV GP HR (EIA; Diassay, Rijswijk, the Netherlands) (5-9) were the first HPV tests to be clinically validated for primary screening on the basis of longitudinal results from large screening studies (10). Testing for high-risk HPV (hrHPV) nucleic acids is also useful for triage of women with equivocal or mildly abnormal cytology for colposcopy and as a test of cure of treatment (10).Several novel HPV tests have been fully or partially validated by showing noninferiority to HC2 or EIA and high reproducibility (11), as has been extensively reviewed by Arbyn et al. (10) and reported in additional studies (12)(13)(14). These tests usually detect around 14 hrHPVs in aggregate, but some provide concurrent (partial) genotype-specific information. Concurrent genotyping for HPV16 and HPV18 could be beneficial for the triage of hrHPV-positive women (15), as the...

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“…It is based on type-specific E6/E7 DNA target detection using the BD Viper LT platform (BD Diagnostics, Sparks, MD, USA). The assay simultaneously detects 13 high-risk genotypes and one possibly carcinogenic HPV genotype (HPV66) (13); it provides genotyping information on six individual genotypes (16,18,31,45, 51, and 52) and reports the remaining eight HPV genotypes in three distinct groups (33/58, 56/59/66, and 35/39/68). The assay has an internal human beta globin (HBB) gene control for sample sufficiency and assay performance.…”

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Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions

et al. 2015

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Human papillomavirus (HPV) is the etiological agent for the development of cervical cancer and its precursor lesions (1): a persistent infection with high-risk (HR) HPV types has been established as a necessary step in the progression from precancerous to neoplastic disease (2). It is widely recognized that different HR HPV genotypes have different oncogenic potential, with genotype 16 being the most oncogenic of the cancer-causing HPV genotypes (3, 4).For decades, the test of choice for the detection of cervical intraepithelial neoplasia (CIN) was the Pap smear (5). However, the Pap test has severe limitations: a relatively low sensitivity for detection of disease (range, 51 to 74%, depending on the study), limited reproducibility, interobserver variability, and finally the occurrence of equivocal results (6). The advent of HPV testing has introduced an epochal change in cervical cancer screening: in recent years, we observed a gradual shift in the use of HPV test from a "triage test," in case of equivocal cytology, or as an adjunct test to cytology in women older than 30 years, to a primary screening test. This introduction of molecular HPV testing is slowly changing the premise of cervical screening, promising better performance than cytology-based screening but also posing new challenges (7). Over the last 7 years, HPV testing has gained a foothold in a number of national screening programs, most notably in triage of equivocal cytology or as an adjunct test to cytology in women older than 30 years, as well as more recently as a primary screening modality. Four European randomized control trials (RCTs), as recently summarized by Ronco and colleagues, clearly demonstrate the benefit of HPV testing over the use of the Pap smear (8). In this scenario, the performance of the HPV testing system of choice is crucial: the key is for an HPV assay to have an optimal balance between sensitivity and specificity for detection of CIN grade 2 or 3 (CIN2ϩ) lesions in order to identify virtually all women with immediate precursors or in rare cases cervical cancer, and at the same time not to result in too many screening false-positive samples (9, 10). The advantage of HPV testing relies on its high sensitivity, Ն95% for CIN2ϩ lesions, which translates into a high negative predictive value (NPV) allowing for extended screening intervals without increased risk of cervical cancer: HPV-negative women have a reduced risk for CIN2/3 lesions and cancer in the subsequent screening round as demonstrated by the European RCTs (8).Several in-house HPV DNA detection methods have been successfully used in research laboratories worldwide for more than 2 decades, and some have been employed for diagnostic purposes in countries where "nonapproved" tests for routine clinical testing are allowed (11). Recently, new tests using microarrays or real-time PCRs have been developed: the majority of them have been designed to

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Clinical Validation of the BD Onclarity? HPV Assay Using a Non-Inferiority Test

Cited by 15 publications

References 20 publications

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

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

Clinical Evaluation of a GP5+/6+-Based Luminex Assay Having Full High-Risk Human Papillomavirus Genotyping Capability and an Internal Control

Comparison of Onclarity Human Papillomavirus (HPV) Assay with Hybrid Capture II HPV DNA Assay for Detection of Cervical Intraepithelial Neoplasia Grade 2 and 3 Lesions

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