Triage of high-risk human papillomavirus-positive women by methylated POU4F3
Autor: | Yaw Wen Hsu, Hung Cheng Lai, Cheng Chang Chang, Po Hsuan Su, Yu Chih Chen, Hui Chen Wang, Yu Ping Liao, Rui Lan Huang, Par Bahadur Pun |
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Rok vydání: | 2015 |
Předmět: |
Human Papillomavirus Positive
Cervical cancer DNA methylation Referral business.industry Research HrHPV test Biomarker Bioinformatics Cervical cancer screening medicine.disease Triage Human genetics Cervical intraepithelial neoplasia (CIN) QMSP Genetics Medicine Biomarker (medicine) business Molecular Biology Genetics (clinical) Developmental Biology |
Zdroj: | Clinical Epigenetics |
ISSN: | 1868-7075 |
Popis: | 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. Electronic supplementary material The online version of this article (doi:10.1186/s13148-015-0122-0) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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