Clinical Performance of the BD Onclarity HPV Assay
Clinical Performance of the BD Onclarity HPV Assay
Objectives: To compare the performance of the BD Onclarity HPV Assay (BD Diagnostics, Sparks, MD) in BD SurePath liquid-based cytology media with that of Hybrid Capture 2 (HC2, Qiagen, Germantown, MD) samples co-collected in specimen transport medium in an adjudicated patient cohort.
Methods: The performance of the BD Onclarity HPV Assay using BD SurePath media was compared with that of HC2 samples co-collected in specimen transport medium using 541 archived samples from a multicenter US clinical trial with histologically adjudicated cervical biopsy specimens.
Results: The sensitivity for cervical intraepithelial neoplasia (CIN) 2 positivity (n - 104) was 90.4% (95% confidence interval [CI], 83–95) and 93.3% (95% CI, 87–97) and specificity was 76.9% (95% CI, 73–81) and 77.8% (95% CI, 74–82) for the BD assay and HC2, respectively. Nine cases of CIN 2+ had results discordant with the high-risk HPV assay. All were found to have been correctly classified with the BD assay using a novel WAVE denaturing high-performance liquid chromatography double-stranded DNA sequencing method.
Conclusions: The clinical performance of The BD Onclarity HPV Assay with respect to histology end points was similar to HC2. Moreover, discordant analysis revealed improved performance of the BD assay with respect to ability to provide extended genotyping information and lack of cross-reactivity with low-risk HPV types associated with cellular abnormalities. The relative risks for CIN 3 disease for HPV 31 and HPV 33/58 (combined) were comparable to that of HPV 18 in this population, suggesting that these genotypes may warrant monitoring in future studies.
The advancement of molecular technologies has led to the introduction of a number of tests that specifically detect high-risk human papillomaviruses (hrHPV). The Hybrid Capture 2 (HC2) HPV DNA test (HC2, Qiagen, Germantown, MD) was the first molecular test to be approved by the Food and Drug Administration (FDA) and is widely used both as an adjunct to cytology for cervical cancer screening and as a way to determine which women with minor cytologic abnormalities require colposcopy. Most recent studies have clearly shown that hrHPV testing alone is significantly more sensitive than cytology for detecting cervical cancer and is only slightly less specific. In addition, a growing body of evidence now shows that cervical cytology together with hrHPV testing offers little benefit over hrHPV testing alone. A number of countries are now moving to adopt hrHPV primary screening with a reflex to cytology or genotyping as a triage method for hrHPV-positive women. Primary screening with hrHPV testing will require a highly accurate hrHPV test, because it alone will be used to determine which women need additional follow-up and which women can simply be rescreened at some interval. Moreover, although many hrHPV tests may exhibit acceptable clinical sensitivity, the specificity of hrHPV tests will also be important when hrHPV testing is used for primary screening. This is because even a small decrease in specificity will lead to increases in unnecessary referrals for follow-up, avoidable anxiety for patients, and a substantial increased cost to the health care system.
Once we begin to use hrHPV testing for primary screening, some form of triage will be required to reduce the number of HPV-positive women needing referral to colposcopy. A number of different triage strategies are being considered. Triage using cytology and/or genotyping for specific hrHPVs most commonly found in association with cervical intraepithelial neoplasia (CIN) type 3 lesions and invasive cancers has been reported to have the best outcome in terms of avoiding unnecessary colposcopy referrals. However, cytology has well-recognized limitations including both a false-positive rate (because of infection with low-risk HPV and non–HPV-associated cellular abnormalities) and a high false-negative rate (because of sampling and detection errors). Moreover, commonly used genotyping assays also have limitations. A large World Health Organization (WHO) global proficiency study of HPV genotyping tests reported a relatively low sensitivity for both HPV 16 and HPV 18 when they occurred in mixed HPV infections. Therefore, it is important that the next generation of hrHPV testing methods have maximal clinically valid sensitivity without compromising on specificity and that they provide robust and accurate detection of the most important HPV genotypes when present in both single and mixed HPV infections.
The BD Onclarity HPV Assay (BD Diagnostics, Sparks, MD) is a new real-time polymerase chain reaction (PCR)–based HPV screening test, which targets the E6 and E7 DNA regions of the HPV genome. These target regions are required during all stages of disease progression and the assay is designed to enable the detection of type-specific regions of the virus, as opposed to consensus amplification of conserved genomic regions detected with L1 primer sets. The assay can provide individual genotyping information for six HPV types, while simultaneously screening for all 14 high-risk virus types. The six genotypes identified individually with the assay include HPV 16, 18, 31, 45, 51, and 52. The performance of the BD assay has previously been reported to be equivalent to a number of FDA-approved and European conformity (CE)–marked HPV assays (including HC2) using cervical specimens collected in PreservCyt medium (Hologic, Marlborough, MA). Here we evaluate the performance of the BD Onclarity HPV Assay using cervical specimens collected in BD SurePath medium and compare its performance to that of HC2 using cervical specimens collected at the same visit in specimen transport medium (STM).
Abstract and Introduction
Abstract
Objectives: To compare the performance of the BD Onclarity HPV Assay (BD Diagnostics, Sparks, MD) in BD SurePath liquid-based cytology media with that of Hybrid Capture 2 (HC2, Qiagen, Germantown, MD) samples co-collected in specimen transport medium in an adjudicated patient cohort.
Methods: The performance of the BD Onclarity HPV Assay using BD SurePath media was compared with that of HC2 samples co-collected in specimen transport medium using 541 archived samples from a multicenter US clinical trial with histologically adjudicated cervical biopsy specimens.
Results: The sensitivity for cervical intraepithelial neoplasia (CIN) 2 positivity (n - 104) was 90.4% (95% confidence interval [CI], 83–95) and 93.3% (95% CI, 87–97) and specificity was 76.9% (95% CI, 73–81) and 77.8% (95% CI, 74–82) for the BD assay and HC2, respectively. Nine cases of CIN 2+ had results discordant with the high-risk HPV assay. All were found to have been correctly classified with the BD assay using a novel WAVE denaturing high-performance liquid chromatography double-stranded DNA sequencing method.
Conclusions: The clinical performance of The BD Onclarity HPV Assay with respect to histology end points was similar to HC2. Moreover, discordant analysis revealed improved performance of the BD assay with respect to ability to provide extended genotyping information and lack of cross-reactivity with low-risk HPV types associated with cellular abnormalities. The relative risks for CIN 3 disease for HPV 31 and HPV 33/58 (combined) were comparable to that of HPV 18 in this population, suggesting that these genotypes may warrant monitoring in future studies.
Introduction
The advancement of molecular technologies has led to the introduction of a number of tests that specifically detect high-risk human papillomaviruses (hrHPV). The Hybrid Capture 2 (HC2) HPV DNA test (HC2, Qiagen, Germantown, MD) was the first molecular test to be approved by the Food and Drug Administration (FDA) and is widely used both as an adjunct to cytology for cervical cancer screening and as a way to determine which women with minor cytologic abnormalities require colposcopy. Most recent studies have clearly shown that hrHPV testing alone is significantly more sensitive than cytology for detecting cervical cancer and is only slightly less specific. In addition, a growing body of evidence now shows that cervical cytology together with hrHPV testing offers little benefit over hrHPV testing alone. A number of countries are now moving to adopt hrHPV primary screening with a reflex to cytology or genotyping as a triage method for hrHPV-positive women. Primary screening with hrHPV testing will require a highly accurate hrHPV test, because it alone will be used to determine which women need additional follow-up and which women can simply be rescreened at some interval. Moreover, although many hrHPV tests may exhibit acceptable clinical sensitivity, the specificity of hrHPV tests will also be important when hrHPV testing is used for primary screening. This is because even a small decrease in specificity will lead to increases in unnecessary referrals for follow-up, avoidable anxiety for patients, and a substantial increased cost to the health care system.
Once we begin to use hrHPV testing for primary screening, some form of triage will be required to reduce the number of HPV-positive women needing referral to colposcopy. A number of different triage strategies are being considered. Triage using cytology and/or genotyping for specific hrHPVs most commonly found in association with cervical intraepithelial neoplasia (CIN) type 3 lesions and invasive cancers has been reported to have the best outcome in terms of avoiding unnecessary colposcopy referrals. However, cytology has well-recognized limitations including both a false-positive rate (because of infection with low-risk HPV and non–HPV-associated cellular abnormalities) and a high false-negative rate (because of sampling and detection errors). Moreover, commonly used genotyping assays also have limitations. A large World Health Organization (WHO) global proficiency study of HPV genotyping tests reported a relatively low sensitivity for both HPV 16 and HPV 18 when they occurred in mixed HPV infections. Therefore, it is important that the next generation of hrHPV testing methods have maximal clinically valid sensitivity without compromising on specificity and that they provide robust and accurate detection of the most important HPV genotypes when present in both single and mixed HPV infections.
The BD Onclarity HPV Assay (BD Diagnostics, Sparks, MD) is a new real-time polymerase chain reaction (PCR)–based HPV screening test, which targets the E6 and E7 DNA regions of the HPV genome. These target regions are required during all stages of disease progression and the assay is designed to enable the detection of type-specific regions of the virus, as opposed to consensus amplification of conserved genomic regions detected with L1 primer sets. The assay can provide individual genotyping information for six HPV types, while simultaneously screening for all 14 high-risk virus types. The six genotypes identified individually with the assay include HPV 16, 18, 31, 45, 51, and 52. The performance of the BD assay has previously been reported to be equivalent to a number of FDA-approved and European conformity (CE)–marked HPV assays (including HC2) using cervical specimens collected in PreservCyt medium (Hologic, Marlborough, MA). Here we evaluate the performance of the BD Onclarity HPV Assay using cervical specimens collected in BD SurePath medium and compare its performance to that of HC2 using cervical specimens collected at the same visit in specimen transport medium (STM).
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