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 |
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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 |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmed_primary_31390052</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2417260410</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4434-d3783022aade349a42be52ebd14df29929ade4fa9fff83ca9641a5ca86a01e513</originalsourceid><addsrcrecordid>eNp1kcGKFDEQhoMo7rh68AWkwYseeieVpLsnHoRhcHVlRRA9h5p0tZuhuzMm3TPMzUfwGX0S0zProoIQSIX6-KjUz9hT4BfAuZi7jb2QogR1j82A6yrnAor7bJZ6PK9AlmfsUYwbzgEKrh6yMwlSc16IGesulx9AL9W8c59AqJ_ff4iso-Hm0OLgfJ-56ewwuh1llsLOWWwzi32qX2XLLNAQfNySHY5AqmNSxOnt-0TufWjrvaspi8NYHx6zBw22kZ7c3ufsy-Wbz6t3-fXHt1er5XVulZIqr2W1kFwIxJqk0qjEmgpB6xpU3QithU4N1aBummYhLepSARYWFyVyoALkOXt98m7HdUe1pX4I2JptcB2Gg_HozN-d3t2Yr35nKrmYNpMEL24FwX8bKQ6mc9FS22JPfoxGiFJLXZaqSOjzf9CNH0P6fKIUVKLkCibhyxN13FGg5m4Y4GYK0aQQzTHExD77c_o78ndqCZifgL1r6fB_k7l6vzopfwEcTajm</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2417260410</pqid></control><display><type>article</type><title>FAM19A4/miR124‐2 methylation in invasive cervical cancer: A retrospective cross‐sectional worldwide study</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><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.</creator><creatorcontrib>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.</creatorcontrib><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.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.32614</identifier><identifier>PMID: 31390052</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>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</subject><ispartof>International journal of cancer, 2020-08, Vol.147 (4), p.1215-1221</ispartof><rights>2019 The Authors. published by John Wiley & Sons Ltd on behalf of UICC</rights><rights>2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.</rights><rights>2019. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4434-d3783022aade349a42be52ebd14df29929ade4fa9fff83ca9641a5ca86a01e513</citedby><cites>FETCH-LOGICAL-c4434-d3783022aade349a42be52ebd14df29929ade4fa9fff83ca9641a5ca86a01e513</cites><orcidid>0000-0003-4853-6747 ; 0000-0001-6463-7391 ; 0000-0002-2327-9839 ; 0000-0001-7534-333X ; 0000-0002-2604-3928 ; 0000-0003-2178-2403 ; 0000-0002-4951-9167</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fijc.32614$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fijc.32614$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31390052$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vink, Frederique J.</creatorcontrib><creatorcontrib>Meijer, Chris J.L.M.</creatorcontrib><creatorcontrib>Clifford, Gary M.</creatorcontrib><creatorcontrib>Poljak, Mario</creatorcontrib><creatorcontrib>Oštrbenk, Anja</creatorcontrib><creatorcontrib>Petry, Karl Ulrich</creatorcontrib><creatorcontrib>Rothe, Beate</creatorcontrib><creatorcontrib>Bonde, Jesper</creatorcontrib><creatorcontrib>Pedersen, Helle</creatorcontrib><creatorcontrib>Sanjosé, Silvia</creatorcontrib><creatorcontrib>Torres, Montserrat</creatorcontrib><creatorcontrib>Pino, Marta</creatorcontrib><creatorcontrib>Quint, Wim G.V.</creatorcontrib><creatorcontrib>Cuschieri, Kate</creatorcontrib><creatorcontrib>Boada, Elia Alcañiz</creatorcontrib><creatorcontrib>Trommel, Nienke E.</creatorcontrib><creatorcontrib>Lissenberg‐Witte, Birgit I.</creatorcontrib><creatorcontrib>Floore, Arno N.</creatorcontrib><creatorcontrib>Hesselink, Albertus T.</creatorcontrib><creatorcontrib>Steenbergen, Renske D.M.</creatorcontrib><creatorcontrib>Bleeker, Maaike C.G.</creatorcontrib><creatorcontrib>Heideman, Daniëlle A.M.</creatorcontrib><title>FAM19A4/miR124‐2 methylation in invasive cervical cancer: A retrospective cross‐sectional worldwide study</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><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.</description><subject>biomarker</subject><subject>Cancer</subject><subject>Cervical cancer</subject><subject>Cervical carcinoma</subject><subject>cervical screening</subject><subject>Cervix</subject><subject>Cross-Sectional Studies</subject><subject>Cytokines - genetics</subject><subject>DNA hypermethylation</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>human genome methylation</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16 - genetics</subject><subject>Human papillomavirus 16 - physiology</subject><subject>Human papillomavirus 18 - genetics</subject><subject>Human papillomavirus 18 - physiology</subject><subject>Humans</subject><subject>Invasiveness</subject><subject>Mass Screening - methods</subject><subject>Medical research</subject><subject>MicroRNAs - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vink, Frederique J.</au><au>Meijer, Chris J.L.M.</au><au>Clifford, Gary M.</au><au>Poljak, Mario</au><au>Oštrbenk, Anja</au><au>Petry, Karl Ulrich</au><au>Rothe, Beate</au><au>Bonde, Jesper</au><au>Pedersen, Helle</au><au>Sanjosé, Silvia</au><au>Torres, Montserrat</au><au>Pino, Marta</au><au>Quint, Wim G.V.</au><au>Cuschieri, Kate</au><au>Boada, Elia Alcañiz</au><au>Trommel, Nienke E.</au><au>Lissenberg‐Witte, Birgit I.</au><au>Floore, Arno N.</au><au>Hesselink, Albertus T.</au><au>Steenbergen, Renske D.M.</au><au>Bleeker, Maaike C.G.</au><au>Heideman, Daniëlle A.M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FAM19A4/miR124‐2 methylation in invasive cervical cancer: A retrospective cross‐sectional worldwide study</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2020-08-15</date><risdate>2020</risdate><volume>147</volume><issue>4</issue><spage>1215</spage><epage>1221</epage><pages>1215-1221</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>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.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & 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> |
fulltext | fulltext |
identifier | ISSN: 0020-7136 |
ispartof | International journal of cancer, 2020-08, Vol.147 (4), p.1215-1221 |
issn | 0020-7136 1097-0215 |
language | eng |
recordid | cdi_pubmed_primary_31390052 |
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 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T15%3A32%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=FAM19A4/miR124%E2%80%902%20methylation%20in%20invasive%20cervical%20cancer:%20A%20retrospective%20cross%E2%80%90sectional%20worldwide%20study&rft.jtitle=International%20journal%20of%20cancer&rft.au=Vink,%20Frederique%20J.&rft.date=2020-08-15&rft.volume=147&rft.issue=4&rft.spage=1215&rft.epage=1221&rft.pages=1215-1221&rft.issn=0020-7136&rft.eissn=1097-0215&rft_id=info:doi/10.1002/ijc.32614&rft_dat=%3Cproquest_pubme%3E2417260410%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2417260410&rft_id=info:pmid/31390052&rfr_iscdi=true |