Abstract

Objective:To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV.Design:Post-hoc analysis using data from a South African study cohort.Methods:Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome.Results:Cytology provided highest specificity (91.6%), but lowest sensitivity (59.3%), whereas a single HPV test provided highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1%) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9%). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7%, specificity 74.8%). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test).Conclusion:Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.
Original languageEnglish
Pages (from-to)2035-2042
Number of pages8
JournalAIDS
Volume33
Issue number13
Early online date2 Aug 2019
DOIs
Publication statusPublished - 1 Nov 2019

Cite this

Kremer, Wieke W. ; van Zummeren, Marjolein ; Breytenbach, Erika ; Richter, Karin L. ; Steenbergen, Renske D. M. ; Meijer, Chris J. L. M. ; Dreyer, Greta. / The use of molecular markers for cervical screening of women living with HIV in South Africa. In: AIDS. 2019 ; Vol. 33, No. 13. pp. 2035-2042.
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title = "The use of molecular markers for cervical screening of women living with HIV in South Africa",
abstract = "Objective:To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV.Design:Post-hoc analysis using data from a South African study cohort.Methods:Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome.Results:Cytology provided highest specificity (91.6{\%}), but lowest sensitivity (59.3{\%}), whereas a single HPV test provided highest sensitivity (83.1{\%}), but lowest specificity (66.4{\%}). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1{\%}) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9{\%}). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7{\%}, specificity 74.8{\%}). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test).Conclusion:Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.",
keywords = "Africa, DNA methylation, HIV, cervical intraepithelial neoplasia, early detection of cancer, human papillomavirus",
author = "Kremer, {Wieke W.} and {van Zummeren}, Marjolein and Erika Breytenbach and Richter, {Karin L.} and Steenbergen, {Renske D. M.} and Meijer, {Chris J. L. M.} and Greta Dreyer",
year = "2019",
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The use of molecular markers for cervical screening of women living with HIV in South Africa. / Kremer, Wieke W.; van Zummeren, Marjolein; Breytenbach, Erika; Richter, Karin L.; Steenbergen, Renske D. M.; Meijer, Chris J. L. M.; Dreyer, Greta.

In: AIDS, Vol. 33, No. 13, 01.11.2019, p. 2035-2042.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The use of molecular markers for cervical screening of women living with HIV in South Africa

AU - Kremer, Wieke W.

AU - van Zummeren, Marjolein

AU - Breytenbach, Erika

AU - Richter, Karin L.

AU - Steenbergen, Renske D. M.

AU - Meijer, Chris J. L. M.

AU - Dreyer, Greta

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Objective:To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV.Design:Post-hoc analysis using data from a South African study cohort.Methods:Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome.Results:Cytology provided highest specificity (91.6%), but lowest sensitivity (59.3%), whereas a single HPV test provided highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1%) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9%). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7%, specificity 74.8%). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test).Conclusion:Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.

AB - Objective:To determine the performance of molecular screening strategies for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) in comparison with cytology screening in women living with HIV.Design:Post-hoc analysis using data from a South African study cohort.Methods:Cytology and human papillomavirus (HPV)-based strategies were evaluated, including single test and FAM19A4/miR124-2 methylation triage strategies. Participants underwent cytology screening and a colposcopy-directed biopsy. Valid results on cytology, HPV status, 16/18 genotyping and histology were available for 318 women. Detection of HPV and FAM19A4/miR124-2 hypermethylation was performed on DNA from cervical scrapes. Histological diagnosis of CIN3+ was used as outcome.Results:Cytology provided highest specificity (91.6%), but lowest sensitivity (59.3%), whereas a single HPV test provided highest sensitivity (83.1%), but lowest specificity (66.4%). Combining cytology with methylation did not improve the performance compared with cytology alone: a slight increase in sensitivity was seen, at the cost of a decrease in specificity. Triage of high-risk HPV positive women with methylation increased specificity (76.1%) compared with a single HPV or cytology test, while maintaining acceptable sensitivity (72.9%). Similar performance was observed for HPV16/18 with methylation triage (sensitivity 79.7%, specificity 74.8%). The number of women needed to refer to detect one CIN3+ ranged from 1.5 (cytology) to 2.6 (single HPV test).Conclusion:Molecular screening strategies using HPV, with or without HPV16/18 genotyping, and FAM19A4/miR124-2 methylation have higher sensitivity with an acceptable loss in specificity compared with current cytology screening and are efficient for the detection of CIN3+ in South African women living with HIV.

KW - Africa

KW - DNA methylation

KW - HIV

KW - cervical intraepithelial neoplasia

KW - early detection of cancer

KW - human papillomavirus

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31385866

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DO - 10.1097/QAD.0000000000002325

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EP - 2042

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