FAM19A4/miR124‐2 methylation in invasive cervical cancer: A retrospective cross‐sectional worldwide study

Widespread adoption of primary human papillomavirus (HPV)‐based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124‐2 gene...

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Veröffentlicht in:International journal of cancer 2020-08, Vol.147 (4), p.1215-1221
Hauptverfasser: Vink, Frederique J., Meijer, Chris J.L.M., Clifford, Gary M., Poljak, Mario, Oštrbenk, Anja, Petry, Karl Ulrich, Rothe, Beate, Bonde, Jesper, Pedersen, Helle, Sanjosé, Silvia, Torres, Montserrat, Pino, Marta, Quint, Wim G.V., Cuschieri, Kate, Boada, Elia Alcañiz, Trommel, Nienke E., Lissenberg‐Witte, Birgit I., Floore, Arno N., Hesselink, Albertus T., Steenbergen, Renske D.M., Bleeker, Maaike C.G., Heideman, Daniëlle A.M.
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container_end_page 1221
container_issue 4
container_start_page 1215
container_title International journal of cancer
container_volume 147
creator Vink, Frederique J.
Meijer, Chris J.L.M.
Clifford, Gary M.
Poljak, Mario
Oštrbenk, Anja
Petry, Karl Ulrich
Rothe, Beate
Bonde, Jesper
Pedersen, Helle
Sanjosé, Silvia
Torres, Montserrat
Pino, Marta
Quint, Wim G.V.
Cuschieri, Kate
Boada, Elia Alcañiz
Trommel, Nienke E.
Lissenberg‐Witte, Birgit I.
Floore, Arno N.
Hesselink, Albertus T.
Steenbergen, Renske D.M.
Bleeker, Maaike C.G.
Heideman, Daniëlle A.M.
description Widespread adoption of primary human papillomavirus (HPV)‐based screening has encouraged the search for a triage test which retains high sensitivity for the detection of cervical cancer and precancer, but increases specificity to avoid overtreatment. Methylation analysis of FAM19A4 and miR124‐2 genes has shown promise for the triage of high‐risk (hr) HPV‐positive women. In our study, we assessed the consistency of FAM19A4/miR124‐2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation‐specific PCR (qMSP)‐based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7–99.2) tested FAM19A4/miR124‐2 methylation‐positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124‐2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV‐negative carcinomas. These results indicate that a negative FAM19A4/miR124‐2 methylation assay result is likely to rule out the presence of cervical cancer. What's new? Methylation analysis of host cell genes is a promising strategy for the triage of women who test positive for high‐risk human papillomavirus (hrHPV). Its ability to consistently detect cervical cancer, however, warrants further evaluation. In this retrospective cross‐sectional study of more than 500 cervical cancer cases worldwide, methylation analysis using FAM19A4 and miR124‐2 genes successfully detected the vast majority of cervical carcinomas. Detection by FAM19A4/miR124‐2 methylation analysis was consistent regardless of multiple factors, including hrHPV status and genotype, cancer histotype, sample type, and geographical region. The findings suggest that a negative FAM19A4/miR124‐2 methylation test result is likely to rule out cervical cancer.
doi_str_mv 10.1002/ijc.32614
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In conclusion, FAM19A4/miR124‐2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV‐negative carcinomas. These results indicate that a negative FAM19A4/miR124‐2 methylation assay result is likely to rule out the presence of cervical cancer. What's new? Methylation analysis of host cell genes is a promising strategy for the triage of women who test positive for high‐risk human papillomavirus (hrHPV). Its ability to consistently detect cervical cancer, however, warrants further evaluation. In this retrospective cross‐sectional study of more than 500 cervical cancer cases worldwide, methylation analysis using FAM19A4 and miR124‐2 genes successfully detected the vast majority of cervical carcinomas. Detection by FAM19A4/miR124‐2 methylation analysis was consistent regardless of multiple factors, including hrHPV status and genotype, cancer histotype, sample type, and geographical region. 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In conclusion, FAM19A4/miR124‐2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV‐negative carcinomas. These results indicate that a negative FAM19A4/miR124‐2 methylation assay result is likely to rule out the presence of cervical cancer. What's new? Methylation analysis of host cell genes is a promising strategy for the triage of women who test positive for high‐risk human papillomavirus (hrHPV). Its ability to consistently detect cervical cancer, however, warrants further evaluation. In this retrospective cross‐sectional study of more than 500 cervical cancer cases worldwide, methylation analysis using FAM19A4 and miR124‐2 genes successfully detected the vast majority of cervical carcinomas. Detection by FAM19A4/miR124‐2 methylation analysis was consistent regardless of multiple factors, including hrHPV status and genotype, cancer histotype, sample type, and geographical region. 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Methylation analysis of FAM19A4 and miR124‐2 genes has shown promise for the triage of high‐risk (hr) HPV‐positive women. In our study, we assessed the consistency of FAM19A4/miR124‐2 methylation analysis in the detection of cervical cancer in a series of 519 invasive cervical carcinomas (n = 314 cervical scrapes, n = 205 tissue specimens) from over 25 countries, using a quantitative methylation‐specific PCR (qMSP)‐based assay (QIAsure Methylation Test®). Positivity rates stratified per histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region were calculated. In total, 510 of the 519 cervical carcinomas (98.3%; 95% CI: 96.7–99.2) tested FAM19A4/miR124‐2 methylation‐positive. Test positivity was consistent across the different subgroups based on cervical cancer histotype, FIGO stage, hrHPV status, hrHPV genotype, sample type and geographical region. In conclusion, FAM19A4/miR124‐2 methylation analysis detects nearly all cervical carcinomas, including rare histotypes and hrHPV‐negative carcinomas. These results indicate that a negative FAM19A4/miR124‐2 methylation assay result is likely to rule out the presence of cervical cancer. What's new? Methylation analysis of host cell genes is a promising strategy for the triage of women who test positive for high‐risk human papillomavirus (hrHPV). Its ability to consistently detect cervical cancer, however, warrants further evaluation. In this retrospective cross‐sectional study of more than 500 cervical cancer cases worldwide, methylation analysis using FAM19A4 and miR124‐2 genes successfully detected the vast majority of cervical carcinomas. Detection by FAM19A4/miR124‐2 methylation analysis was consistent regardless of multiple factors, including hrHPV status and genotype, cancer histotype, sample type, and geographical region. The findings suggest that a negative FAM19A4/miR124‐2 methylation test result is likely to rule out cervical cancer.</abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>31390052</pmid><doi>10.1002/ijc.32614</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-4853-6747</orcidid><orcidid>https://orcid.org/0000-0001-6463-7391</orcidid><orcidid>https://orcid.org/0000-0002-2327-9839</orcidid><orcidid>https://orcid.org/0000-0001-7534-333X</orcidid><orcidid>https://orcid.org/0000-0002-2604-3928</orcidid><orcidid>https://orcid.org/0000-0003-2178-2403</orcidid><orcidid>https://orcid.org/0000-0002-4951-9167</orcidid><oa>free_for_read</oa></addata></record>
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ispartof International journal of cancer, 2020-08, Vol.147 (4), p.1215-1221
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1097-0215
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source MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects biomarker
Cancer
Cervical cancer
Cervical carcinoma
cervical screening
Cervix
Cross-Sectional Studies
Cytokines - genetics
DNA hypermethylation
DNA Methylation
Female
Genotype
Genotypes
human genome methylation
Human papillomavirus
Human papillomavirus 16 - genetics
Human papillomavirus 16 - physiology
Human papillomavirus 18 - genetics
Human papillomavirus 18 - physiology
Humans
Invasiveness
Mass Screening - methods
Medical research
MicroRNAs - genetics
Papillomavirus Infections - diagnosis
Papillomavirus Infections - genetics
Papillomavirus Infections - virology
Retrospective Studies
Sensitivity analysis
Tumor Markers and Signatures
Uterine Cervical Dysplasia
Uterine Cervical Neoplasms - diagnosis
Uterine Cervical Neoplasms - genetics
Uterine Cervical Neoplasms - virology
Vaginal Smears - methods
title FAM19A4/miR124‐2 methylation in invasive cervical cancer: A retrospective cross‐sectional worldwide study
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