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Journal article
Performance of CADM1, MAL and miR124-2 methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea
BMJ Open, Vol.14(6), pp.1-11
2024
PMID: 38904134
Abstract
Objective: WHO recommends human papillomavirus (HPV) testing for cervical screening, with triage of high-risk HPV (hrHPV) positive women. However, there are limitations to effective triage for low-resource, high-burden settings, such as Papua New Guinea. In this exploratory study, we assessed the performance of host methylation as triage tools for predicting high-grade squamous intraepithelial lesions (HSIL) in self-collected and clinician-collected samples.
Design: Exploratory observational study.
Setting: Provincial hospital, same-day cervical screen-and-treat trial, Papua New Guinea.
Participants: 44 hrHPV+women, with paired self/clinician-collected samples (4 squamous cell carcinomas (SCC), 19 HSIL, 4 low-grade squamous intraepithelial lesions, 17 normal).
Primary and secondary outcome measures: Methylation levels of CADM1, MAL and miR124-2 analysed by methylation-specific PCRs against the clinical endpoint of HSIL or SCC (HSIL+) measured using liquid-based-cytology/p16-Ki67 stain.
Results: In clinician-collected samples, MAL and miR124-2 methylation levels were significantly higher with increasing grade of disease (p=0.0046 and p<0.0015, respectively). miR124-2 was the best predictor of HSIL (area under the curve, AUC 0.819) while MAL of SCC (AUC 0.856). In self-collected samples, MAL best predicted HSIL (AUC 0.595) while miR124-2 SCC (AUC 0.812). Combined miR124-2/MAL methylation yielded sensitivity and specificity for HSIL+ of 90.5% (95% CI 69.6% to 98.8%) and 70% (95% CI 45.7% to 88.1%), respectively, in clinician-collected samples, and 81.8% (95% CI 59.7% to 94.8%) and 47.6% (95% CI 25.7% to 70.2%), respectively, in self-collected samples. miR124-2/MAL plus HPV16/HPV18 improved sensitivity for HSIL+ (95.2%, 95% CI 76.2% to 99.9%) but decreased specificity (55.0%, 95% CI 31.5% to 76.9%).
Conclusion: miR124-2/MAL methylation is a potential triage strategy for the detection of HSIL/SCC in low-income and middle-income country.
Details
- Title
- Performance of CADM1, MAL and miR124-2 methylation as triage markers for early detection of cervical cancer in self-collected and clinician-collected samples: an exploratory observational study in Papua New Guinea
- Authors
- Monica Molano (Corresponding Author) - Royal Women's HospitalDorothy A Machalek - UNSW SydneyGrace Tan - Australian Centre for the Prevention of Cervical Cancer (Australia)Suzanne M Garland - Royal Women's HospitalPrisha Balgovind - Murdoch Children's Research InstituteGholamreza Haqshenas - The University of MelbourneGloria M. Munnull - Papua New Guinea Institute of Medical ResearchSamuel Phillips - Murdoch Children's Research InstituteSteven G Badman - UNSW SydneyJohn Bolnga - Papua New Guinea Institute of Medical ResearchAlyssa M Cornall - Murdoch Children's Research InstituteJosephine Gabuzzi - Papua New Guinea Institute of Medical ResearchZure Kombati - Mount Hagen Provincial HospitalJulia ML Brotherton - The University of MelbourneMarion Saville - Australian Centre for the Prevention of Cervical Cancer (Australia)David Hawkes - Australian Centre for the Prevention of Cervical Cancer (Australia)John M. Kaldor - UNSW SydneyPamela J. Toliman - UNSW SydneyAndrew J. Vallely - UNSW SydneyGerald Murray - The University of Melbourne
- Publication details
- BMJ Open, Vol.14(6), pp.1-11
- Publisher
- BMJ Group
- Date published
- 2024
- DOI
- 10.1136/bmjopen-2023-081282
- ISSN
- 2044-6055
- PMID
- 38904134
- Copyright note
- This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
- Data Availability
- Data are available on reasonable request. Limited data may be available on reasonable request from the corresponding author, subject to ethical approval.
- Grant note
- This work was funded through the National Health and Medical Research Council, Australia, (NHMRC) grants 1013209 and 1104938 (AJV), Government of Papua New Guinea (ICRAS 297/1), the NHMRC Centre for Research Excellence in Cervical Cancer Control APP1135172 (JBr, MS, AJV, SG, JK, DAM and DH) and NHMRC Investigator Grant APP1197951 (SG).
- Organisation Unit
- School of Health - Biomedicine; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991144231302621
- Output Type
- Journal article