TY - JOUR
T1 - Role of FAM19A4/miR124-2 methylation analysis in predicting regression or non-regression of CIN2/3 lesions: A protocol of an observational longitudinal cohort study
T2 - a protocol of an observational longitudinal cohort study
AU - Kremer, Wieke W.
AU - Berkhof, Johannes
AU - Bleeker, Maaike C. G.
AU - Heideman, Daniëlle A. M.
AU - van Trommel, Nienke E.
AU - van Baal, Marchien W.
AU - Verhoeve, Harold R.
AU - Meijer, Chris J. L. M.
AU - Kenter, Gemma G.
N1 - © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Introduction: The clinical course of high-grade cervical intraepithelial neoplasia (CIN2/3) is characterised by a high spontaneous regression rate. Histological assessment is unable to differentiate between CIN2/3 lesions likely to regress and those likely to persist or progress. Most CIN2/3 lesions are treated by surgical excision, leading to overtreatment of a substantial proportion. In this prospective study, we evaluate the value of DNA methylation of host cell genes, which has shown to be particularly sensitive for the detection of advanced CIN2/3 and cervical cancer, in the prediction of regression or non-regression of CIN2/3 lesions. Methods and analysis: This is a multicentre observational longitudinal study with 24-month follow-up. Women referred for colposcopy with an abnormal cervical scrape, who have been diagnosed with CIN2/3 and a small cervical lesion (≤50% of cervix) will be asked to participate. Participants will be monitored by 6-monthly cytological and colposcopic examination. In case of clinical progression, participants will receive treatment and exit the study protocol. At baseline and during follow-up, self-sampled cervicovaginal brushes and cervical scrapes will be collected for high-risk human papillomavirus (HPV) testing and FAM19A4/miR124-2 methylation analysis. A colposcopy-directed biopsy will be taken from all participants at the last follow-up visit. The primary study endpoint is regression or non-regression at the end of the study based on the histological diagnosis. Regression is defined as CIN1 or less. Non-regression is defined as CIN2 or worse. The secondary study endpoint is defined as HPV clearance (double-negative HPV test at two consecutive time-points). The association between methylation status and regression probability will be evaluated by means of χ2 testing. Ethics and dissemination: Ethics approval was obtained in all participating clinics. Results: of the main study will be submitted for publication in a peer-reviewed journal.
AB - Introduction: The clinical course of high-grade cervical intraepithelial neoplasia (CIN2/3) is characterised by a high spontaneous regression rate. Histological assessment is unable to differentiate between CIN2/3 lesions likely to regress and those likely to persist or progress. Most CIN2/3 lesions are treated by surgical excision, leading to overtreatment of a substantial proportion. In this prospective study, we evaluate the value of DNA methylation of host cell genes, which has shown to be particularly sensitive for the detection of advanced CIN2/3 and cervical cancer, in the prediction of regression or non-regression of CIN2/3 lesions. Methods and analysis: This is a multicentre observational longitudinal study with 24-month follow-up. Women referred for colposcopy with an abnormal cervical scrape, who have been diagnosed with CIN2/3 and a small cervical lesion (≤50% of cervix) will be asked to participate. Participants will be monitored by 6-monthly cytological and colposcopic examination. In case of clinical progression, participants will receive treatment and exit the study protocol. At baseline and during follow-up, self-sampled cervicovaginal brushes and cervical scrapes will be collected for high-risk human papillomavirus (HPV) testing and FAM19A4/miR124-2 methylation analysis. A colposcopy-directed biopsy will be taken from all participants at the last follow-up visit. The primary study endpoint is regression or non-regression at the end of the study based on the histological diagnosis. Regression is defined as CIN1 or less. Non-regression is defined as CIN2 or worse. The secondary study endpoint is defined as HPV clearance (double-negative HPV test at two consecutive time-points). The association between methylation status and regression probability will be evaluated by means of χ2 testing. Ethics and dissemination: Ethics approval was obtained in all participating clinics. Results: of the main study will be submitted for publication in a peer-reviewed journal.
KW - DNA methylation
KW - cervical intraepithelial neoplasia
KW - colposcopy
KW - human papillomavirus
KW - natural history
KW - overtreatment
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85068841858&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31289088
UR - http://www.scopus.com/inward/record.url?scp=85068841858&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/bmjopen-2019-029017
DO - https://doi.org/10.1136/bmjopen-2019-029017
M3 - Article
C2 - 31289088
SN - 2044-6055
VL - 9
SP - e029017
JO - BMJ Open
JF - BMJ Open
IS - 7
M1 - e029017
ER -