Disagreement between Human Papillomavirus Assays: An Unexpected Challenge for the Choice of an Assay in Primary Cervical Screening

Rebolj, Matejka; Preisler, Sarah; Ejegod, Ditte Møller; Rygaard, Carsten; Lynge, Elsebeth; Bonde, Jesper

doi:10.1371/journal.pone.0086835

Cited by 63 publications

(78 citation statements)

References 31 publications

(18 reference statements)

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“…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. Furthermore, in the U.S. study, the cytological samples were in SurePath preservative fluid, which might have had a bearing on the results (25). In future VALGENT iterations, we aim to include formal histological review and also sample sets collected in SurePath fluid, which will address these potential confounders directly.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2015

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“…The design of the Horizon study was described in detail previously [8][9][10][11][12]. Consecutive SurePath samples from 5034 women arriving for routine LBC analysis at the Department of Pathology of Copenhagen University Hospital, Hvidovre, in June-August 2011 were tested with the four HPV assays.…”

Section: Methodsmentioning

confidence: 99%

“…All assay testing was undertaken in strict accordance with the protocols agreed upon with all manufacturers prior to the study, described in detail previously [8][9][10][11][12]. HC2 testing was undertaken on the post-quot LBC material; cobas, CLART and APTIMA testing were undertaken on the original residual material, diluted approximately 1:1 in SurePath.…”

Section: Hpv Testingmentioning

confidence: 99%

A daunting challenge: Human Papillomavirus assays and cytology in primary cervical screening of women below age 30years

Bonde¹,

Ejegod²,

Preisler³

et al. 2015

European Journal of Cancer

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We compared cytology with Hybrid Capture 2 (HC2), cobas, CLART and APTIMA Human Papillomavirus (HPV) assays in primary cervical screening at age 23-29 years based on data from the Danish Horizon study. SurePath samples were collected from 1278 women undergoing routine cytology-based screening. Abnormal cytology was managed according to the routine recommendations, and women with cytology-normal/HPV-positive samples were invited for repeated cytology and HPV testing in 1.5 years. Loss to follow-up was similar between HPV assays. ⩾ CIN3 was detected in 44 women. The sensitivity of HC2 for ⩾ CIN3 was 95% (95% confidence interval (CI): 85-99), of cobas 98% (95% CI: 88-100), of CLART 100% (95% CI: 92-100), of APTIMA 82% (95% CI: 67-92), and of cytology 59% (95% CI: 43-74). Specificity for ⩾ CIN3 varied between 61% (95% CI: 59-64) for cobas and 75% (95% CI: 73-78) for APTIMA, and was 94% (95% CI: 93-96) for cytology. Similar results were observed for ⩾ CIN2 (N = 68). HPV screening with cytological triage doubled the number of colposcopies compared to cytology screening, and increased the frequency of repeated testing by four (APTIMA) to seven (cobas) times. The positive predictive value of a referral for colposcopy was relatively high for all screening tests (⩾ 30% for ⩾ CIN3, and ⩾ 50% for ⩾ CIN2). CIN1 was detected by cytology in ∼ 1% of women, and in ∼ 2% by any of the four HPV assays. Although highly sensitive, HPV-based screening of young Danish women should be approached cautiously, as it resulted in large reductions in specificity, and increased the demand for additional testing.

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“…In HPV positive, cytology negative women, who represent the vast majority of HPV positive cases, the disagreement was even larger. These patients should be considered at higher risk, and a prolonged rescreening interval would not be advisable; but at the same time it is known that this risk is still relatively low, and a 6-12 months retesting would lead to repeated visits in a large group of women who might have tested negative had they been screened with another HPV assay [30].…”

Section: Background Studiesmentioning

confidence: 99%

Reconsidering Primary HPV Testing in Cervical Cancer Screening

Liverani¹

2015

JLS

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Abstract:Inappropriate testing for HPV types on healthy subjects increases costs without benefit and potentially results in overtreatment. HPV testing also has a negative psychosocial impact on women, increasing anxiety, stress, and concerns on sexual relationships. Giving the fact that HPV testing has been shown to have similar sensitivity but more overdiagnosis than cytology, and also giving the fact that false negative results may be higher than previously suspected, primary screening with HPV tests in European countries should be reconsidered. Resources saved in molecular testing may well be addressed in implementing vaccination strategies which are still underused, and may possibly include males as well as women.

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Disagreement between Human Papillomavirus Assays: An Unexpected Challenge for the Choice of an Assay in Primary Cervical Screening

Cited by 63 publications

References 31 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

A daunting challenge: Human Papillomavirus assays and cytology in primary cervical screening of women below age 30years

Reconsidering Primary HPV Testing in Cervical Cancer Screening

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