The Onclarity Human Papillomavirus Trial: Design, methods, and baseline results

Stoler, Mark H.; Wright, Thomas; Parvu, Valentin; Vaughan, Laurence M.; Yanson, Karen; Eckert, Karen; Karchmer, Tobi B.; Kodsi, Salma; Cooper, Charles K.

doi:10.1016/j.ygyno.2018.04.007

Cited by 59 publications

(74 citation statements)

References 27 publications

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“…[8][9][10] In contrast, the prevalence of precancer, defined as cervical intraepithelial neoplasia grade 3 (CIN3) and adenocarcinoma in situ (AIS), is on the order of 0.5-1%. 11,12 As it is neither possible nor clinically desirable to refer all HPV-positive women to colposcopy, a triage strategy for HPV-positive women is needed to identify the women who would benefit most from immediate referral to colposcopy. For example, in the Netherlands, a target referral rate of 2% of screened women is considered "ideal," producing a ratio of 2-4 colposcopies per CIN3 detected.…”

Section: Introductionmentioning

confidence: 99%

“…Recent epidemiologic data have shown that the risk of CIN3 for some of those 12-other hrHPV genotypes, such as HPV31 or 33, is on par with HPV18. 11,17 Therefore, following the concept of equal management for equal risk, questions have arisen as to how extended genotyping might shift the balance among the two screening groups created by triage of screen positives: those referred for immediate colposcopy and those who can safely be deferred for follow-up testing after 12 months.…”

Section: Introductionmentioning

confidence: 99%

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Approaches to triage optimization in HPV primary screening: Extended genotyping and p16/Ki‐67 dual‐stained cytology—Retrospective insights from ATHENA

Stoler

Baker

Boyle

et al. 2019

Intl Journal of Cancer

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The objective of our study was to assess the performance of different triage strategies for high‐risk human papillomavirus (hrHPV)‐positive results utilizing either extended genotyping or a p16/Ki‐67 dual‐stained cytology (DS) approach, with or without partial genotyping. A subset of women with hrHPV infections participating in the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study were analyzed to determine the number of cervical intraepithelial neoplasia grade 3 or worse (≥CIN3) cases detected, and the absolute risk for ≥CIN3 of each genotype. A clinical utility table was constructed to compare the impact of different triage strategies. In all, 2,339 women with single‐genotype hrHPV infections were identified. Among these were 171 ≥CIN3 cases. The U.S. Food and Drug Administration (FDA)‐approved algorithm (HPV16/18 positive, or 12‐other hrHPV positive and Pap positive, i.e., ≥ atypical squamous cells of undetermined significance) for primary HPV screening detected 132/171 (77.2%) ≥CIN3 cases and required 964 colposcopies (colposcopies per ≥CIN3 ratio: 7.3). An approach that uses DS instead of cytology in the FDA‐approved algorithm detected 147/171 (86.0%) ≥CIN3 cases, requiring 1,012 colposcopies (ratio: 6.9). Utilizing DS for triage of all hrHPV‐positive women identified 126/171 (73.7%) ≥CIN3 cases, requiring 640 colposcopies (ratio: 5.1). A strategy that detected HPV16/18/31/33/35+ captured 130/171 (76.0%) ≥CIN3 cases, requiring 1,025 colposcopies (ratio: 7.9). Inclusion of additional genotypes resulted in greater disease detection at the expense of higher colposcopy ratios. Substituting cytology with a DS triage approach improved disease detection and the colposcopy detection rate. Further reduction of colposcopy rates can be achieved by using DS without partial genotyping. Extended genotyping strategies can identify a comparable number of cases but requires an increased number of colposcopies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Approaches to triage optimization in HPV primary screening: Extended genotyping and p16/Ki‐67 dual‐stained cytology—Retrospective insights from ATHENA

Stoler

Baker

Boyle

et al. 2019

Intl Journal of Cancer

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“…The BD Onclarity™ HPV Assay provides results on an automated platform (BD Viper LT™ System) and offers genotyping with individual reporting 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. The Onclarity HPV test is internationally validated on both SurePath and Thinprep LBC media for use in primary HPV screening and has recently received FDA approval for primary screening in women over 25 years in the United States . To investigate the risk of disease arising from the individual HPV genotypes, we used Bayesian data analysis which provides a natural and principled way of modeling risk in subjects with multiple genotype infections.…”

Section: Introductionmentioning

confidence: 99%

Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Bonde

Bottari

Parvu

et al. 2019

Intl Journal of Cancer

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Whereas HPV16 and HPV18 have been the focus in current risk‐based cervical cancer screening algorithms using HPV genotype information, mounting evidence suggests that oncogenic HPV types such as HPV31, 33, 52 and 58 pose a ≥CIN3 risk equivalent to or greater than that of HPV18, and the combined risk of HPV31 and HPV33 rivals even HPV16 in women above 30 years of age. Here, we evaluate the baseline risk of CIN2 and CIN3 by genotype in a colposcopy referral population from Denmark and Italy. In total, 655 women were enrolled upon a referral to colposcopy after a positive screening sample. All samples were HPV analyzed using Onclarity HPV assay with extended genotyping and combined with the histology outcomes, a Bayesian probability modeling was used to determine the risk per genotype assessed. The combined data for this referral population showed that the ≥CIN2 risk of HPV16 was 69.1%, HPV31 at 63.3%, HPV33/58 at 52.7%, HPV18 at 46.6% and HPV52 at 40.8%. For ≥CIN3, the risks were 44.3%, 38.5%, 36.8%, 30.9% and 16.8% for HPV16, HPV31, HPV18, HPV33/58 and HPV52, respectively, indicating that the baseline risk of disease arising from HPV16 is, not surprisingly, the highest among the oncogenic HPV genotypes. We find that the HPV genotype‐specific ≥CIN2 and ≥CIN3 risk‐patterns are so distinct that, for example, 35/39/68 and 56/59/66 should be considered only for low intensive follow‐up, thereby proposing active use of this information in triage strategies for screening HPV‐positive women.

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“…12,13 Many HR-HPV screening tests have since been developed to improve upon the performance of HC2 test. 14,18,19 In this study, we reported the promising result of such an effort. CerviHPV results in terms of the levels and types of HPV infection, thus confirming very low levels of HR-HPV infection in these cases ( The methodology and design of CerviHPV test are very similar to those of another widely used HR-HPV detection assay, cobas HPV Test (cobasHPV), 30 which was the first HR-HPV test approved by FDA for primary cervical cancer screening.…”

Section: Discussionmentioning

confidence: 73%

“…Third, it has been well documented that HC2 probes can cross react with many LR‐HPV types, leading to false positive result . Many HR‐HPV screening tests have since been developed to improve upon the performance of HC2 test . In this study, we reported the promising result of such an effort.…”

Section: Discussionmentioning

confidence: 79%

Comparison of CerviHPV and Hybrid Capture 2 HPV tests for detection of high‐risk HPV infection in cervical swab specimens

Zhao

Tian

et al. 2018

Diagnostic Cytopathology

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Background Persistent high‐risk human papillomavirus (HR‐HPV) infection is the etiological cause of virtually all cervical cancer cases. HR‐HPV screening achieved with earlier generations of HR‐HPV tests has been instrumental in the prevention and early detection of cervical cancer worldwide. The first FDA‐approved HR‐HPV test, digene Hybrid Capture 2 HPV DNA Test (HC2), has been prominent in these efforts. Newer tests have since been developed to improve upon the capability of HC2 test. Methods To evaluate the performance of a new multiplex real‐time quantitative PCR assay for HR‐HPV detection, CerviHPV HR‐HPV Test (CerviHPV), 232 cervical swab specimens were collected and analyzed by HC2 and CerviHPV tests for comparison. Results HC2 test detected 69 (29.7%) positive cases, whereas CerviHPV test reported 43 (18.5%) positive cases. The concordance rate between the two tests was 84.5% with a kappa value of 0.579. Additional analyses identified only HPV66 or low‐risk HPV (LR‐HPV) types in six HC2 positive discordant cases, suggesting these HC2 results to be false positive. Conclusion CerviHPV test has two advantages over HC2 test: It contains a cellular control to eliminate false negative results due to failed sample collection and processing, and it can simultaneously detect and genotype the two most carcinogenic HPV types, HPV16 and 18. In this comparison study, CerviHPV test also demonstrated higher analytical specificity for HR‐HPV genotypes than HC2 test. Therefore, CerviHPV test has the potential to become a viable option for cervical cancer screening in the clinics.

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The Onclarity Human Papillomavirus Trial: Design, methods, and baseline results

Cited by 59 publications

References 27 publications

Approaches to triage optimization in HPV primary screening: Extended genotyping and p16/Ki‐67 dual‐stained cytology—Retrospective insights from ATHENA

Approaches to triage optimization in HPV primary screening: Extended genotyping and p16/Ki‐67 dual‐stained cytology—Retrospective insights from ATHENA

Bayesian analysis of baseline risk of CIN2 and ≥CIN3 by HPV genotype in a European referral cohort

Comparison of CerviHPV and Hybrid Capture 2 HPV tests for detection of high‐risk HPV infection in cervical swab specimens

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