Bioanalysis Zone

Ongoing clinical trial indicates potential for a combined approach in diagnosing cervical cancer


Encouraging results have been published in the International Journal of Cancer in a review of an ongoing clinical trial assessing the combined use of DNA methylation biomarker detection and high-risk HPV testing as a potential screening option for cervical cancer.

The ongoing study, the Triage and Risk Assessment of Cervical Precancer by Epigenetic Biomarker (TRACE), is evaluating a methylation-specific assay for the gene POU4F3 and comparing results to a cytology-based triage.  TRACE is a multicenter clinical study and involves analyzing cervical samples from over 6000 women, analyzed by complex molecular assays. The research team aim to validate the CONFIDENCE™ assay, including both the CONFIDENCE HPV™ and the CONFIDENCE Marker™ tests.

Researchers are also assessing the clinical performance and aptitude of the CONFIDENCE Marker™ test, a human epigenetic biomarker test which measures the methylation level of a target gene by quantitative methylation-specific real-time PCR.

The POU4F3 promoter is known as a candidate marker for high-grade HPV-positive cervical intraepithelial lesions (CIN3+). When methylated, POU4F3 analysis alone showed much higher sensitivity and specificity than liquid-based cytology, with comparable specificity.

Although the trial is currently being run in outpatient and oncology center study populations and therefore may be criticized for not accurately assessing a screening population, the authors acknowledge that further trials in a follow-up phase may validate these results and confirm the clinical performance of POU4F3 DNA methylation.

The authors conclude that the quantitative nature of the combination of the assays show potential for the development of a more objective risk assessment tool in the screening of women for cervical cancer and precancer, as well as in the prevention, diagnosis and management of CIN3+.

Source: Kocsis A, Takács T, Jeney C et al. Performance of a new HPV and biomarker assay in the management of hrHPV positive women: Subanalysis of the ongoing multicenter TRACE clinical trial (n > 6,000) to evaluate POU4F3 methylation as a potential biomarker of cervical precancer and cancer. Int. J. Cancer, 140: 1119–1133 (2017);


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