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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.

journal_name

Clin Epigenetics

journal_title

Clinical epigenetics

authors

Pun PB,Liao YP,Su PH,Wang HC,Chen YC,Hsu YW,Huang RL,Chang CC,Lai HC

doi

10.1186/s13148-015-0122-0

subject

Has Abstract

pub_date

2015-08-21 00:00:00

pages

85

eissn

1868-7075

issn

1868-7083

pii

122

journal_volume

7

pub_type

杂志文章

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