The use of molecular markers for cervical screening of women living with hiv in South Africa

Wieke W Kremer, Marjolein Van Zummeren, Erika Breytenbach, Karin L Richter, Renske D M Steenbergen, Chris J L M Meijer, Greta Dreyer

Research output: Contribution to journalArticleAcademicpeer-review

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 (WLHIV).

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).

CONCLUSIONS: 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 WLHIV.

Original languageEnglish
JournalAIDS (London, England)
DOIs
Publication statusE-pub ahead of print - 2 Aug 2019

Cite this

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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 (WLHIV).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).CONCLUSIONS: 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 WLHIV.",
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",
month = "8",
day = "2",
doi = "10.1097/QAD.0000000000002325",
language = "English",
journal = "AIDS (London, England)",
issn = "1473-5571",

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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 (London, England), 02.08.2019.

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 - 2019/8/2

Y1 - 2019/8/2

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 (WLHIV).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).CONCLUSIONS: 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 WLHIV.

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 (WLHIV).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).CONCLUSIONS: 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 WLHIV.

U2 - 10.1097/QAD.0000000000002325

DO - 10.1097/QAD.0000000000002325

M3 - Article

JO - AIDS (London, England)

JF - AIDS (London, England)

SN - 1473-5571

ER -