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Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus
BACKGROUND: Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907555/ https://www.ncbi.nlm.nih.gov/pubmed/36366827 http://dx.doi.org/10.1093/cid/ciac801 |
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author | Vink, Frederique J Meijer, Chris J L M Lissenberg-Witte, Birgit I Visser, Cathy Duin, Sylvia Snyman, Leon C Richter, Karin L van der Merwe, Frederick H Botha, Matthys H Steenbergen, Renske D M Dreyer, Greta |
author_facet | Vink, Frederique J Meijer, Chris J L M Lissenberg-Witte, Birgit I Visser, Cathy Duin, Sylvia Snyman, Leon C Richter, Karin L van der Merwe, Frederick H Botha, Matthys H Steenbergen, Renske D M Dreyer, Greta |
author_sort | Vink, Frederique J |
collection | PubMed |
description | BACKGROUND: Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH. METHODS: In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher. RESULTS: Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%–93.6%) and 89.7% (83.0%–96.5%), respectively, and specificities of 72.9% (67.3%–78.5%) and 75.0% (69.5%–80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82–.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02–1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01–1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90–1.003]). CONCLUSIONS: Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing. |
format | Online Article Text |
id | pubmed-9907555 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-99075552023-02-09 Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus Vink, Frederique J Meijer, Chris J L M Lissenberg-Witte, Birgit I Visser, Cathy Duin, Sylvia Snyman, Leon C Richter, Karin L van der Merwe, Frederick H Botha, Matthys H Steenbergen, Renske D M Dreyer, Greta Clin Infect Dis Major Article BACKGROUND: Compared with women who are human immunodeficiency virus (HIV) negative, women with human immunodeficiency virus (WWH) have a higher human papillomavirus (HPV) prevalence and increased cervical cancer risk, emphasizing the need for effective cervical cancer screening in this population. The present study aimed to validate methylation markers ASCL1 and LHX8 for primary screening in a South African cohort of WWH. METHODS: In this post hoc analysis within the DIAgnosis in Vaccine And Cervical Cancer Screen (DiaVACCS) study, a South African observational multicenter cohort study, cervical scrape samples from 411 HIV-positive women were analyzed for hypermethylation of ASCL1 and LHX8 genes, HPV DNA, and cytology. Sensitivities, specificities, and positive and negative predictive values of primary methylation-based, HPV-based and cytology-based screening were calculated for the detection of cervical intraepithelial neoplasia of grade 3 or higher. RESULTS: Single markers ASCL1 and LHX8 resulted in a good performance for the detection of cervical intraepithelial neoplasia of grade 3 or higher, with sensitivities of 85.9% (95% confidence interval [CI], 78.2%–93.6%) and 89.7% (83.0%–96.5%), respectively, and specificities of 72.9% (67.3%–78.5%) and 75.0% (69.5%–80.5%). Combining markers ASCL1 and LHX8 resulted in a lower sensitivity compared with HPV testing (84.6% vs 93.6%, respectively; ratio, 0.90 [95% CI, .82–.99]) and a higher specificity (86.7% vs 78.3%; ratio 1.11 [1.02–1.20]) and reduced the referral rate from 46.8% to 33.4%. ASCL1/LHX8 methylation had a significantly higher sensitivity than cytology (threshold, high-grade intraepithelial squamous lesion or worse), (84.6% vs 74.0%, respectively; ratio, 1.16 [95% CI, 1.01–1.32]) and similar specificity (86.7% vs 91.0%; ratio, 0.95 [.90–1.003]). CONCLUSIONS: Our results validate the accuracy of ASCL1/LHX8 methylation analysis for primary screening in WWH, which offers a full-molecular alternative to cytology- or HPV-based screening, without the need for additional triage testing. Oxford University Press 2022-11-11 /pmc/articles/PMC9907555/ /pubmed/36366827 http://dx.doi.org/10.1093/cid/ciac801 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Article Vink, Frederique J Meijer, Chris J L M Lissenberg-Witte, Birgit I Visser, Cathy Duin, Sylvia Snyman, Leon C Richter, Karin L van der Merwe, Frederick H Botha, Matthys H Steenbergen, Renske D M Dreyer, Greta Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus |
title | Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus |
title_full | Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus |
title_fullStr | Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus |
title_full_unstemmed | Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus |
title_short | Validation of ASCL1 and LHX8 Methylation Analysis as Primary Cervical Cancer Screening Strategy in South African Women with Human Immunodeficiency Virus |
title_sort | validation of ascl1 and lhx8 methylation analysis as primary cervical cancer screening strategy in south african women with human immunodeficiency virus |
topic | Major Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9907555/ https://www.ncbi.nlm.nih.gov/pubmed/36366827 http://dx.doi.org/10.1093/cid/ciac801 |
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