Cervical screening programs using cervical cytology, are or will be replaced by primary hrHPV testing in several countries. Women who test hrHPV-positive require a secondary (triage) test to prevent over-referral and over-treatment. Analysis of DNA methylation of host cell tumor suppressor genes in cervical scrapes provides promising triage strategy for hrHPV-positive women. Urine collection is expected to increase the uptake of cervical screening programs, and hrHPV testing in urine appears promising. We aimed to test whether DNA methylation analysis in urine provides a novel more patient-friendly strategy to detect cervical cancer.
Cervical scrapes and urine samples from cervical cancer patients and healthy female controls (n=40 each) were tested for hrHPV DNA presence and DNA methylation of 6 genes with known performance of cervical (pre)cancer detection in cervical scrapes.
A high concordance was found between hrHPV DNA testing on cervical scrapes and urine samples. Also DNA methylation levels in paired cervical scrapes and urine samples showed a good correlation. DNA methylation levels of all 6 genes were significantly increased in urine samples of cervical cancer patients compared to controls. Receiver operating characteristics (ROC) analysis of the 6 methylation markers in urine showed AUCs ranging from 0.88 to 0.95.
DNA methylation testing in urine is feasible and has a high accuracy to detect cervical cancer. These data warrant further exploration of methylation markers in urine-based cervical screening programs.