TY - JOUR
T1 - Methylation testing for the detection of recurrent cervical intraepithelial neoplasia
AU - Dick, Stèfanie
AU - Heideman, Daniëlle A. M.
AU - Mom, Constantijne H.
AU - Meijer, Chris J. L. M.
AU - Berkhof, Johannes
AU - Steenbergen, Renske D. M.
AU - Bleeker, Maaike C. G.
N1 - Funding Information: The original study was supported by a grant from The Netherlands Cancer Society (KWF VU 2009‐4413) and the European Research Council (ERC advanced 2012‐AdG, proposal 322986 Mass‐care). These funding sources had no involvement in study design, the collection, analysis and interpretation of data, the writing of the report and the decision to submit the paper for publication. Publisher Copyright: © 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.
PY - 2023/12/15
Y1 - 2023/12/15
N2 - Women treated for CIN2/3 remain at increased risk of recurrent CIN and cervical cancer, and therefore posttreatment surveillance is recommended. This post hoc analysis evaluates the potential of methylation markers ASCL1/LHX8 and FAM19A4/miR124-2 for posttreatment detection of recurrent CIN2/3. Cervical scrapes taken at 6 and 12 months posttreatment of 364 women treated for CIN2/3 were tested for methylation of ASCL1/LHX8 and FAM19A4/miR124-2 using quantitative multiplex methylation-specific PCR. Performance of the methylation tests were calculated and compared with the performance of HPV and/or cytology. Methylation levels of recurrent CIN were compared between women with a persistent HPV infection, and women with an incident HPV infection or without HPV infection. Recurrent CIN2/3 was detected in 42 women (11.5%), including 28 women with CIN2 and 14 with CIN3. ASCL1/LHX8 tested positive in 13/14 (92.9%) of recurrent CIN3 and 13/27 (48.1%) of recurrent CIN2. FAM19A4/miR124-2 tested positive in 14/14 (100%) of recurrent CIN3 and 10/27 (37.0%) of recurrent CIN2. Combined HPV and/or methylation testing showed similar positivity rates as HPV and/or cytology. The CIN2/3 risk at 12 months posttreatment was 30.8% after a positive ASCL1/LHX8 result at 6 months posttreatment. Methylation levels of CIN2/3 in women with a persistent HPV infection were significantly higher compared with women with an incident or no HPV infection. In conclusion, posttreatment monitoring by methylation analysis of ASCL1/LHX8 and FAM19A4/miR124-2 showed a good performance for the detection of recurrent CIN. DNA methylation testing can help to identify women with recurrent CIN that require re-treatment.
AB - Women treated for CIN2/3 remain at increased risk of recurrent CIN and cervical cancer, and therefore posttreatment surveillance is recommended. This post hoc analysis evaluates the potential of methylation markers ASCL1/LHX8 and FAM19A4/miR124-2 for posttreatment detection of recurrent CIN2/3. Cervical scrapes taken at 6 and 12 months posttreatment of 364 women treated for CIN2/3 were tested for methylation of ASCL1/LHX8 and FAM19A4/miR124-2 using quantitative multiplex methylation-specific PCR. Performance of the methylation tests were calculated and compared with the performance of HPV and/or cytology. Methylation levels of recurrent CIN were compared between women with a persistent HPV infection, and women with an incident HPV infection or without HPV infection. Recurrent CIN2/3 was detected in 42 women (11.5%), including 28 women with CIN2 and 14 with CIN3. ASCL1/LHX8 tested positive in 13/14 (92.9%) of recurrent CIN3 and 13/27 (48.1%) of recurrent CIN2. FAM19A4/miR124-2 tested positive in 14/14 (100%) of recurrent CIN3 and 10/27 (37.0%) of recurrent CIN2. Combined HPV and/or methylation testing showed similar positivity rates as HPV and/or cytology. The CIN2/3 risk at 12 months posttreatment was 30.8% after a positive ASCL1/LHX8 result at 6 months posttreatment. Methylation levels of CIN2/3 in women with a persistent HPV infection were significantly higher compared with women with an incident or no HPV infection. In conclusion, posttreatment monitoring by methylation analysis of ASCL1/LHX8 and FAM19A4/miR124-2 showed a good performance for the detection of recurrent CIN. DNA methylation testing can help to identify women with recurrent CIN that require re-treatment.
KW - DNA methylation
KW - cervical cancer
KW - high-grade CIN
KW - posttreatment surveillance
KW - recurrent CIN
UR - http://www.scopus.com/inward/record.url?scp=85166770588&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/ijc.34678
DO - https://doi.org/10.1002/ijc.34678
M3 - Article
C2 - 37539971
SN - 0020-7136
VL - 153
SP - 2011
EP - 2018
JO - International journal of cancer
JF - International journal of cancer
IS - 12
ER -