@article{8eb06068e0c3424abdbad632eeb66420,
title = "Triage of high-risk human papillomavirus-positive women by methylated POU4F3",
abstract = "Background: Insufficient specificity of the high-risk human papillomavirus (hrHPV) assay in primary cervical cancer screening results in unnecessary referral. Additional assays to triage hrHPV-positive women are needed to improve molecular cervical cancer screening. DNA methylation is a promising biomarker in cervical cancer. We evaluated the clinical performance of potentially methylated genes as a triage assay for hrHPV-positive women. Results: We conducted a retrospective hospital-based case–control study in Taiwan. Cervical scrapings were collected before colposcopy for hrHPV testing and quantitative methylation-specific PCR (QMSP) of 16 genes. Five genes, POU4F3, HS3ST2, AJAP1, PAX1, and SOX1, were prioritized for the clinical performance to triage hrHPV-positive women. Two hundred cervical scrapings were randomly classified into a training set (n = 111) and testing set (n = 89). All samples were tested for hrHPV using a Hybrid Capture II (HCII) assay. HrHPV-positive women were subjected to DNA methylation analysis by QMSP. In the training set, the receiver operating characteristic (ROC) curves defined the optimal methylation index (M-index) cutoff values for discriminating CIN3+ from CIN1/normal, which then were applied to the testing set. Among the five genes, POU4F3 revealed the highest area under the ROC curve (AUC) (0.86; 95 % CI, 0.78–0.95) in detecting CIN3+. In the testing set, POU4F3 revealed the best clinical performance in triage of hrHPV-positive women with a sensitivity of 74 % and specificity of 89 % for detecting CIN3+. Conclusions: POU4F3 methylation analysis is a potential molecular tool for triage in detecting CIN3+ in hrHPV-positive women. The combined use of broad-spectrum HPV assay and POU4F3 methylation analysis as a new generation of molecular cervical cancer screening warrants further population-based study.",
keywords = "Biomarker, Cervical cancer screening, Cervical intraepithelial neoplasia (CIN), DNA methylation, HrHPV test, QMSP",
author = "Pun, {Par Bahadur} and Liao, {Yu Ping} and Su, {Po Hsuan} and Wang, {Hui Chen} and Chen, {Yu Chih} and Hsu, {Yaw Wen} and Huang, {Rui Lan} and Chang, {Cheng Chang} and Lai, {Hung Cheng}",
note = "Funding Information: This work was supported in part by the following grants: grant numbers NSC 102-2628-B-038-010-MY3 from the Ministry of Science and Technology; 103TMU-SHH-11, TMU103-AE1-B06, TMUTOP103005-1, and 104TMU-SHH-07 from Taipei Medical University; and TMU-NDMC-104-05 from Taipei Medical University and National Defense Medical Center. This work was also supported by the Teh-Tzer Study Group for Human Medical Research Foundation. PBP is thankful to Taiwan International Graduate program (TIGP) for the PhD Fellowship. Publisher Copyright: {\textcopyright} 2015, Pun et al.",
year = "2015",
month = aug,
day = "21",
doi = "10.1186/s13148-015-0122-0",
language = "English",
volume = "7",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "BioMed Central",
number = "1",
}