Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study
ABSTRACT The use of clinically validated human papillomavirus (HPV) assays is recommended in cervical cancer screening, and extended genotyping is getting attention as a triage biomarker because of the different oncogenic risk of the high-risk HPV genotypes. We compared the results of the Becton &am...
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American Society for Microbiology
2025-01-01
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| Series: | Microbiology Spectrum |
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| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.00897-24 |
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| author | Laura De Marco Simonetta Bisanzi Guglielmo Ronco Pamela Mancuso Francesca Carozzi Elena Allia Raffaella Rizzolo Daniela Gustinucci Helena Frayle Jessica Viti Anna Iossa Elena Cesarini Simonetta Bulletti Basilio Passamonti Silvia Gori Laura Toniolo Francesco Venturelli Annarosa Del Mistro Paolo Giorgi Rossi Maria Benevolo |
| author_facet | Laura De Marco Simonetta Bisanzi Guglielmo Ronco Pamela Mancuso Francesca Carozzi Elena Allia Raffaella Rizzolo Daniela Gustinucci Helena Frayle Jessica Viti Anna Iossa Elena Cesarini Simonetta Bulletti Basilio Passamonti Silvia Gori Laura Toniolo Francesco Venturelli Annarosa Del Mistro Paolo Giorgi Rossi Maria Benevolo |
| author_sort | Laura De Marco |
| collection | DOAJ |
| description | ABSTRACT The use of clinically validated human papillomavirus (HPV) assays is recommended in cervical cancer screening, and extended genotyping is getting attention as a triage biomarker because of the different oncogenic risk of the high-risk HPV genotypes. We compared the results of the Becton & Dickinson (BD) Onclarity HPV assay, on the residual baseline cervico-vaginal specimens of the NTCC2 trial, to those of the screening HPV-DNA assay (Cobas 4800 or HC2) and to cytology, p16/ki67 and E6/E7 mRNA triage results. We genotyped virtually all HPV-positive women and a consecutive sample of HPV-negatives. Among the 3,129 baseline-positives, 75.5% (k = 0.368) were BD-positive, as were 5 of the 333 baseline-negatives (1.5%). The concordance between BD and HPV-DNA screening test was 87% for Cobas (1,250/1,436) and 65.9% for HC2 (1,115/1,693). A higher than the recommended positivity threshold for Onclarity would increase the agreement but would not improve concordance in the overall screening population. Among the baseline-positive cases, we observed an increasing trend of BD positivity with cytology severity (from 71.6% in negative for intraepithelial lesion of malignancy to 95.1% in ASC-H+ samples), with histologically confirmed CIN3 (96.9%), with p16/ki67 dual staining positivity (90.9% among the positive and 69.6% among the negative specimens), and with E6/E7 mRNA positivity (93.4% in the mRNA-positive cases vs 39.7% among the mRNA-negatives). Our findings confirm some disagreement among different HPV assays used for screening. Nevertheless, the agreement is substantial for women with high-grade cytology, histologically confirmed CIN3, and p16/ki67 or mRNA positivity at triage, thus confirming a good clinical performance of all the tests used.The NTCC2 trial is registered as Clinicaltrials.gov identifier NCT01837693.IMPORTANCELarge randomized clinical trials have demonstrated that human papillomavirus (HPV) testing for high-risk types is more effective than cytology in detecting pre-cancerous lesions and preventing cervical cancer. Its use is being implemented in cervical cancer screening in several countries. The most recent guidelines recommend a risk-based management. It is therefore important to assess the individual risk of having/developing high-grade lesions of women testing high-risk HPV-positive. A crucial viral factor influencing the risk is the HPV genotype since different types are associated to different carcinogenetic risks. Understanding the degree of concordance among different assays targeting either HPV presence/type(s) or cellular morphology and proteins’ expression provides knowledge useful to better define how these tests can be used in screening protocols for an effective triage and to anticipate the possible implementation issues. Our study shows that the concordance between tests is higher when the infections have a higher probability of producing a clinically relevant lesion. |
| format | Article |
| id | doaj-art-66a16f00173c4afe825b69c92080d64a |
| institution | Kabale University |
| issn | 2165-0497 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj-art-66a16f00173c4afe825b69c92080d64a2025-01-07T14:04:06ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972025-01-0113110.1128/spectrum.00897-24Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 studyLaura De Marco0Simonetta Bisanzi1Guglielmo Ronco2Pamela Mancuso3Francesca Carozzi4Elena Allia5Raffaella Rizzolo6Daniela Gustinucci7Helena Frayle8Jessica Viti9Anna Iossa10Elena Cesarini11Simonetta Bulletti12Basilio Passamonti13Silvia Gori14Laura Toniolo15Francesco Venturelli16Annarosa Del Mistro17Paolo Giorgi Rossi18Maria Benevolo19Center for Cervical Cancer Screening, City of Health and Science Hospital, Turin, ItalyInstitute for Cancer Research, Prevention and Oncological Network (ISPRO), Florence, ItalyCenter for Cancer Epidemiology and Prevention (CPO), Turin, ItalyEpidemiology Unit, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Reggio Emilia, ItalyInstitute for Cancer Research, Prevention and Oncological Network (ISPRO), Florence, ItalyCenter for Cervical Cancer Screening, City of Health and Science Hospital, Turin, ItalyCenter for Cancer Epidemiology and Prevention (CPO), Turin, ItalyLaboratorio Unico di Screening, USL Umbria 1, Perugia, ItalyIstituto Oncologico Veneto IOV—IRCCS, Padua, ItalyInstitute for Cancer Research, Prevention and Oncological Network (ISPRO), Florence, ItalyInstitute for Cancer Research, Prevention and Oncological Network (ISPRO), Florence, ItalyLaboratorio Unico di Screening, USL Umbria 1, Perugia, ItalyLaboratorio Unico di Screening, USL Umbria 1, Perugia, ItalyLaboratorio Unico di Screening, USL Umbria 1, Perugia, ItalyIstituto Oncologico Veneto IOV—IRCCS, Padua, ItalyULSS6 Euganea, Padua, ItalyEpidemiology Unit, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Reggio Emilia, ItalyIstituto Oncologico Veneto IOV—IRCCS, Padua, ItalyEpidemiology Unit, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, Reggio Emilia, ItalyIRCCS—Regina Elena National Cancer Institute, Rome, ItalyABSTRACT The use of clinically validated human papillomavirus (HPV) assays is recommended in cervical cancer screening, and extended genotyping is getting attention as a triage biomarker because of the different oncogenic risk of the high-risk HPV genotypes. We compared the results of the Becton & Dickinson (BD) Onclarity HPV assay, on the residual baseline cervico-vaginal specimens of the NTCC2 trial, to those of the screening HPV-DNA assay (Cobas 4800 or HC2) and to cytology, p16/ki67 and E6/E7 mRNA triage results. We genotyped virtually all HPV-positive women and a consecutive sample of HPV-negatives. Among the 3,129 baseline-positives, 75.5% (k = 0.368) were BD-positive, as were 5 of the 333 baseline-negatives (1.5%). The concordance between BD and HPV-DNA screening test was 87% for Cobas (1,250/1,436) and 65.9% for HC2 (1,115/1,693). A higher than the recommended positivity threshold for Onclarity would increase the agreement but would not improve concordance in the overall screening population. Among the baseline-positive cases, we observed an increasing trend of BD positivity with cytology severity (from 71.6% in negative for intraepithelial lesion of malignancy to 95.1% in ASC-H+ samples), with histologically confirmed CIN3 (96.9%), with p16/ki67 dual staining positivity (90.9% among the positive and 69.6% among the negative specimens), and with E6/E7 mRNA positivity (93.4% in the mRNA-positive cases vs 39.7% among the mRNA-negatives). Our findings confirm some disagreement among different HPV assays used for screening. Nevertheless, the agreement is substantial for women with high-grade cytology, histologically confirmed CIN3, and p16/ki67 or mRNA positivity at triage, thus confirming a good clinical performance of all the tests used.The NTCC2 trial is registered as Clinicaltrials.gov identifier NCT01837693.IMPORTANCELarge randomized clinical trials have demonstrated that human papillomavirus (HPV) testing for high-risk types is more effective than cytology in detecting pre-cancerous lesions and preventing cervical cancer. Its use is being implemented in cervical cancer screening in several countries. The most recent guidelines recommend a risk-based management. It is therefore important to assess the individual risk of having/developing high-grade lesions of women testing high-risk HPV-positive. A crucial viral factor influencing the risk is the HPV genotype since different types are associated to different carcinogenetic risks. Understanding the degree of concordance among different assays targeting either HPV presence/type(s) or cellular morphology and proteins’ expression provides knowledge useful to better define how these tests can be used in screening protocols for an effective triage and to anticipate the possible implementation issues. Our study shows that the concordance between tests is higher when the infections have a higher probability of producing a clinically relevant lesion.https://journals.asm.org/doi/10.1128/spectrum.00897-24human papillomaviruscervical cancerextended genotypingNTCC2 study |
| spellingShingle | Laura De Marco Simonetta Bisanzi Guglielmo Ronco Pamela Mancuso Francesca Carozzi Elena Allia Raffaella Rizzolo Daniela Gustinucci Helena Frayle Jessica Viti Anna Iossa Elena Cesarini Simonetta Bulletti Basilio Passamonti Silvia Gori Laura Toniolo Francesco Venturelli Annarosa Del Mistro Paolo Giorgi Rossi Maria Benevolo Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study Microbiology Spectrum human papillomavirus cervical cancer extended genotyping NTCC2 study |
| title | Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study |
| title_full | Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study |
| title_fullStr | Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study |
| title_full_unstemmed | Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study |
| title_short | Extended HPV genotyping by the BD Onclarity assay: concordance with screening HPV-DNA assays, triage biomarkers, and histopathology in women from the NTCC2 study |
| title_sort | extended hpv genotyping by the bd onclarity assay concordance with screening hpv dna assays triage biomarkers and histopathology in women from the ntcc2 study |
| topic | human papillomavirus cervical cancer extended genotyping NTCC2 study |
| url | https://journals.asm.org/doi/10.1128/spectrum.00897-24 |
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