Results of a Phase II study suggest that urine-based personalized testing may represent the future of screening for cervical cancer in some women. Published in Cancer Prevention Research, the findings show that a precision medicine panel of host and viral DNA methylation markers can be used to triage women with an abnormal Pap smear to colposcopy.
For the research, the authors tested a biomarker panel in cervical epithelium DNA obtained from 211 women evaluated in a cervical cancer clinic in Chile from 2006 to 2008. The results were then verified in a prospective cohort of 107 women evaluated in a high-risk clinic in Puerto Rico from 2013 to 2015.
Promoter methylation of ZNF516, FKBP6, and INTS1 had 90% sensitivity, 88.9% specificity, 0.94 area under the curve (AUC), 93.1% positive predictive value (PPV), and 84.2% negative predictive value (NPV) in discriminating between cervical brush samples with cervical intraepithelial neoplasia (CIN) grade 2 or higher and samples with no intraepithelial lesions or malignancy (NILM).
Verification of those panel results with liquid-based cervical cytology samples from an independent cohort showed 90.9% sensitivity, 60.9% specificity, 0.90 AUC, 52.6% PPV, and 93.3% NPV, after HPV16-L1 methylation was added to the panel. The researchers used next-generation sequencing results in HPV-positive cultured cells and urine circulating cell-free DNA (ccfDNA) to design assays that showed clinical feasibility in a subset of 40 paired plasma (AUC=0.81) and urine (AUC=0.860 ccfDNA samples from the prospective cohort.
The authors believe that they are “the first to show that a panel of host and viral DNA methylation markers can discriminate between CIN2+ and NILM in multiple body compartments from the same individual: cervical cytology, serum, and urine.” They believe that the 4-gene classifier warrants further study as a molecular biomarker to triage HPV-positive women who have been diagnosed with cervical dysplasia based on cytology and are referred for colposcopy. More work is needed, however, to improve the performance of the biomarkers, the researchers said, and to move the technology forward.