Detection of hypermethylated genes as markers for cervical screening in women living with HIV

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

INTRODUCTION: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa.

METHODS: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects.

RESULTS: Hypermethylation levels of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3+ ) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75% specificity, CIN3+ sensitivity was 72.1% for ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored positive for these two markers.

CONCLUSIONS: Hypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3+ , warranting further exploration of these methylation markers as a stand-alone test for cervical screening in low-resource settings.

Original languageEnglish
Pages (from-to)e25165
JournalJournal of the international aids society
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 2018

Cite this

@article{0ad9b3759ee2413892c901e079a8073a,
title = "Detection of hypermethylated genes as markers for cervical screening in women living with HIV",
abstract = "INTRODUCTION: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa.METHODS: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60{\%} HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects.RESULTS: Hypermethylation levels of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3+ ) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75{\%} specificity, CIN3+ sensitivity was 72.1{\%} for ASCL1 and 73.8{\%} for LHX8 and all samples from women with cervical cancer scored positive for these two markers.CONCLUSIONS: Hypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3+ , warranting further exploration of these methylation markers as a stand-alone test for cervical screening in low-resource settings.",
author = "Kremer, {Wieke W} and {Van Zummeren}, Marjolein and Novianti, {Putri W} and Richter, {Karin L} and Wina Verlaat and Snijders, {Peter Jf} and Heideman, {Dani{\"e}lle Am} and Steenbergen, {Renske Dm} and Greta Dreyer and Meijer, {Chris Jlm}",
note = "{\circledC} 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.",
year = "2018",
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language = "English",
volume = "21",
pages = "e25165",
journal = "Journal of the international aids society",
issn = "1758-2652",
publisher = "International AIDS Society",
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Detection of hypermethylated genes as markers for cervical screening in women living with HIV. / Kremer, Wieke W; Van Zummeren, Marjolein; Novianti, Putri W; Richter, Karin L; Verlaat, Wina; Snijders, Peter Jf; Heideman, Daniëlle Am; Steenbergen, Renske Dm; Dreyer, Greta; Meijer, Chris Jlm.

In: Journal of the international aids society, Vol. 21, No. 8, 08.2018, p. e25165.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Detection of hypermethylated genes as markers for cervical screening in women living with HIV

AU - Kremer, Wieke W

AU - Van Zummeren, Marjolein

AU - Novianti, Putri W

AU - Richter, Karin L

AU - Verlaat, Wina

AU - Snijders, Peter Jf

AU - Heideman, Daniëlle Am

AU - Steenbergen, Renske Dm

AU - Dreyer, Greta

AU - Meijer, Chris Jlm

N1 - © 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

PY - 2018/8

Y1 - 2018/8

N2 - INTRODUCTION: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa.METHODS: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects.RESULTS: Hypermethylation levels of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3+ ) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75% specificity, CIN3+ sensitivity was 72.1% for ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored positive for these two markers.CONCLUSIONS: Hypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3+ , warranting further exploration of these methylation markers as a stand-alone test for cervical screening in low-resource settings.

AB - INTRODUCTION: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa.METHODS: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology endpoints were available for all study subjects.RESULTS: Hypermethylation levels of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The performance for detection of CIN3 or worse (CIN3+ ) as assessed by the area under the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At a threshold corresponding to 75% specificity, CIN3+ sensitivity was 72.1% for ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored positive for these two markers.CONCLUSIONS: Hypermethylation analysis of ASCL1 or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with an acceptable sensitivity and good specificity for CIN3+ , warranting further exploration of these methylation markers as a stand-alone test for cervical screening in low-resource settings.

U2 - 10.1002/jia2.25165

DO - 10.1002/jia2.25165

M3 - Article

VL - 21

SP - e25165

JO - Journal of the international aids society

JF - Journal of the international aids society

SN - 1758-2652

IS - 8

ER -