Cytologic DNA methylation for managing minimally abnormal cervical cancer screening results.

OBJECTIVES

To explore the role of a DNA methylation assay for managing minimally abnormal cervical cancer screening results in a prospective cohort undergoing opportunistic cervical cancer screening.

METHODS

In the cohort of the METHY2 and METHY3 screening studies of women undergoing opportunistic cervical cancer screening, cervical cytology samples were sent for high-risk human papillomavirus (hrHPV) DNA assays, cytologic pathology and methylation assays of PAX1/JAM3 (CISCER). This study evaluated the discriminative power of CISCER in managing women with minimally abnormal cervical cancer screening results for CIN3+. Absolute CIN3+ risks and colposcopy referrals within one screening round were calculated.

RESULTS

A total of 1857 women with minimally abnormal cervical cancer findings had cervical histologic outcomes and were included in the analysis. In women with a minimally abnormal cervical cancer result, the sensitivity and specificity of CISCER was 74.9% (95% confidence interval [CI], 68.3%-81.4%) and 89.1% (95% CI 87.6%-90.6%) for detecting CIN3+. CISCER analysis discriminated well for minimally abnormal cervical cancer results, yielding a CIN3+ risk of 40.5% (95% CI 34.9%-46.2%) after a positive result and a CIN3+ risk of 2.7% (95% CI 2.0%-3.6%) after a negative result.

CONCLUSIONS

In women with a minimally abnormal cervical cancer screening result, the CISCER provides excellent detection of CIN3+. The use of CISCER in women with a minimally abnormal cervical cancer screening result can lead to a substantial reduction in the number of direct colposcopy referrals.