High-risk human papillomavirus (hrHPV)-DNA testing is frequently performed after an abnormal cytology result for the detection of high-grade dysplasia and cervical cancer (termed CIN3+), particularly in women above 30 years of age. Although highly sensitive, hrHPV testing has only limited specificity. Therefore, triaging of women tested HPV-positive is of high relevance, even in case of underlying abnormal cytology. Epigenetic markers based on methylation of specific DNA regions during carcinogenesis may have the potential to provide diagnostic tests for triage.
In a retrospective, cross-sectional study with two gynecological hospitals residual material from cervical scrapes from more than 300 patients with histopathology-confirmed diagnosis were tested with GynTect. For this purpose cellular material was bisulfite-treated, and the GynTect assay using six methylation markers and two internal controls for detecting women with relevant CIN3+ lesions, was performed.
All cancer cases and 66% of CIN3 were detected with the GynTect assay. Among women older than 29 years of age, almost 80% of the CIN3 cases were detected. In the no CIN group, several cases were detected that showed a high methylation grade and a positive p16 result in the corresponding biopsy, suggesting that GynTect may detect an underlying dysplasia very early. Therefore, such cases require clarification. In total, sensitivity and specificity in this cohort for CIN3+ was 68% and 83%, respectively.
GynTect provides a promising diagnostic tool for identifying patients with CIN3+ among hrHPV-positively tested women. A follow-up of all patients having high methylation level in the no CIN group should show that methylation of the GynTect markers is a strong indication for an underlying CIN that requires close monitoring of the corresponding patients.