DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging

Monica Molano; Dorothy A Machalek; Samuel Phillips; Grace Tan; Suzanne M Garland; David Hawkes; Prisha Balgovind; Reza Haqshenas; Steve G. Badman; John Bolnga; Josephine Gabuzzi; Zure Kombati; Gloria M. Munnull; Julia ML Brotherton; Marion Saville; John M. Kaldor; Pamela J. Toliman; Andrew J. Vallely; Gerald Murray

doi:10.1016/j.tvr.2024.200288

Back

DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging

Journal article

Open access

Peer reviewed

DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging

Monica Molano, Dorothy A Machalek, Samuel Phillips, Grace Tan, Suzanne M Garland, David Hawkes, Prisha Balgovind, Reza Haqshenas, Steve G. Badman, John Bolnga, …

Tumour Virus Research, Vol.18, pp.1-12

2024

DOI: https://doi.org/10.1016/j.tvr.2024.200288

PMID: 38960143

Files and links (1)

pdf

1-s2.0-S2666679024000120-main4.00 MBDownload View

Published VersionCC BY V4.0, Open Access

Abstract

Cervical cancer

Diagnostic test

DNA methylation

Epigenetics

Human papillomavirus

Molecular diagnostics

Global methylation analysis of gene promoters is promising for detection of high-grade squamous intraepithelial lesions or worse (HSIL+) in high-risk human papillomavirus (hrHPV)-positive women. However, diagnostic performance of methylation data at individual CpG-sites is limited. We explored methylation for predicting HSIL+ in self- and clinician-collected samples from Papua New Guinea. Methylation of EPB41L3 (1–6 CpG-sites), hTERT (1–10 CpG-sites) and FAM19A4 (1–5 CpG-sites) was assessed through pyrosequencing from 44 HPV+ samples (4 cancers, 19 HSIL, 4 low-grade squamous intraepithelial lesions (LSIL), 17 normal). New primers were designed for FAM19A4 directed to the first exon region not explored previously. In clinician-collected samples, methylation at CpG-sites 4 and 5 of EPB41L3 were the best HSIL predictors (AUC >0.83) and CpG-site 4 for cancer (0.925). Combination of EPB41L3 sites 2/4 plus FAM19A4 site 1 were the best HSIL+ markers [100% sensitivity, 63.2% specificity]. Methylation at CpG-site 5 of FAM19A4 was the best HSIL predictor (0.67) in self-collected samples, and CpG-sites 1 and 3 of FAM19A4 for cancer (0.77). Combined, FAM19A4 site 1 plus HPV 16/18 detection yielded sensitivity of 82.6% and specificity of 61.9%. In conclusion, methylation at individual CpG-sites of EPB41L3 and FAM19A4 outperformed global analysis and improved HSIL+ detection, warranting further investigation.

Details

Title: DNA methylation at individual CpG-sites of EPB41L3, HTERT and FAM19A4 are useful for detection of cervical high-grade squamous intraepithelial lesions (HSIL) or worse: Analysis of individual CpG-sites outperforms averaging
Authors: Monica Molano (Corresponding Author) - Royal Women's Hospital
Dorothy A Machalek - UNSW Sydney
Samuel Phillips - Murdoch Children's Research Institute
Grace Tan - Australian Centre for the Prevention of Cervical Cancer (Australia)
Suzanne M Garland - Royal Women's Hospital
David Hawkes - Australian Centre for the Prevention of Cervical Cancer (Australia)
Prisha Balgovind - Royal Women's Hospital
Reza Haqshenas - Murdoch Children's Research Institute
Steve G. Badman - UNSW Sydney
John Bolnga - Papua New Guinea Institute of Medical Research
Josephine Gabuzzi - Papua New Guinea Institute of Medical Research
Zure Kombati - Mount Hagen Provincial Hospital
Gloria M. Munnull - Papua New Guinea Institute of Medical Research
Julia ML Brotherton - Australian Centre for the Prevention of Cervical Cancer (Australia)
Marion Saville - Australian Centre for the Prevention of Cervical Cancer (Australia)
John M. Kaldor - UNSW Sydney
Pamela J. Toliman - UNSW Sydney
Andrew J. Vallely - UNSW Sydney
Gerald Murray - The University of Melbourne
Publication details: Tumour Virus Research, Vol.18, pp.1-12
Publisher: Elsevier BV
Date published: 2024
DOI: 10.1016/j.tvr.2024.200288
ISSN: 2666-6790
PMID: 38960143
Data Availability: The data that has been used is confidential.
Grant note: This work was funded through the National Health and Medical Research Council, Australia (NHMRC), grants 1,013,209 and 1104938) (AJV), Government of Papua New Guinea (ICRAS 297/1), the NHMRC Centre for Research Excellence in Cervical Cancer Control APP1135172 (JMLB, MS, AJV) and NHMRC Investigator Grant APP1197951 (SMG).
Organisation Unit: School of Health - Biomedicine; Centre for Bioinnovation
Language: English
Record Identifier: 991144231402621
Output Type: Journal article

Metrics

20 Record Views

3 Times Cited - Web of Science

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Virology

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites