Science & Technology

Early results of the clinical trial - HPV 2015 presentation


Epigenetic markers on the horizon: how to triage hrHPV positive women

Baseline results from ongoing cohort study


Adrienn Kocsis (1), Marta Benczik (1,4), Robert Koiss (2), Zsuzsa Schaff (3), Miklos Nyiri (1), Tibor Takacs (1,4)

  1. Cellcall Kft., Budapest, Hungary
  2. Department of Obstetrics and Gynaecology, St. Stephan’s Hospital, Budapest, Hungary
  3. Second Department of Pathology, Semmelweis University, Budapest, Hungary
  4. GenoID Molecular Diagnostic Laboratory, Synlab Hungary Kft., Budapest, Hungary


Objectives. The most recent guidelines recommend primary high-risk human papillomavirus (hrHPV) screening as an alternative to cytology-based cervical cancer screening. Although hrHPV detection has high sensitivity, it is not specific enough, leading to a substantial false positive rate. In our ongoing multicentric clinical study we investigated an epigenetic molecular biomarker, based on host gene methylation, as a potential triage method of HR-HPV positive women.

Methods. Over 2,800 cervical specimens were obtained for liquid-based cytology and hrHPV tests (CONFIDENCE™ HPV and Roche cobas® HPV), from women aged 25 years or older, presenting for cervical screening. Host DNA methylation test (CONFIDENCE™ Marker) was carried out on bisulphite converted DNA. In clinically indicated cases, diagnostic histology was used as a ’gold standard’ reference method. In the absence of histologically confirmed diagnosis, negative histology result was presumed.

Based on the medical history in the two years before the baseline sampling, we stratified women according to risk in two cohorts: screening and risk. In the screening population we have 2188 cases with negative or no history. In the risk group we have 263 cases with hrHPV positivity and/or ASCUS or worse cytology mentioned in the medical history.

Results. We found close to 70% agreement in the hrHPV positive cases with the comparator HPV test. The overall kappa value was 0.77, which is a very good agreement. In the screening population, 22% of the cases was hrHPV positive, but only 4% was also methylation positive. In the risk group, 62% of the samples was hrHPV positive, and half of them was also methylation positive. Considering the distribution of CIN2+ cases, 44 of 49 CIN2 or worse cases was also methylation positive, which means the test proved to be very sensitive.

Conclusion. We recommend sensitive primary HPV screening followed by a triage of positive cases using highly specific molecular biomarkers. Epigenetic approach has potential clinical utility in the management of HR-HPV positive women.

Presented at the 30th International Papillomavirus Conference, Sept 17-21 2015, Lisbon, Portugal.

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