Comparative performance of hrHPV testing and PAX1/ZNF671 methylation in triaging women with abnormal cytology: a study of paired urine, vaginal and cervical scrape samples.
PAX1/ZNF671 methylation testing on cervical scrapes best detects CIN3+ lesions, beating urine/vaginal samples
Comparative performance of hrHPV testing and PAX1/ZNF671 methylation in triaging women with abnormal cytology: a study of paired urine, vaginal and cervical scrape samples.
The purpose was to evaluate the diagnostic effectiveness of High-risk human papillomavirus(hrHPV) testing, DNA methylation, PAX1/ZNF671 methylation in triaging patients with abnormal cytology and/or abnormal cervical biopsy pathology in cervical cancer screening; And the detection performance of different screening strategies was compared among clinician-taken cervical scrapes and paired self-collected urine and vaginal samples.
A total of 136 urine-based,137self-collected vaginal and 140 cervical scrapes samples were analyzed.
cervical scrapes caught more cin3+ than urine or vaginal samples
For PAX1 and ZNF671, the areas under the ROC curve were 0.929 and 0.862 and the methylation-positive rate was 89.5% (77/86) and 80.2% (69/86) in CIN3+ lesions.
The sensitivity of hrHPV testing for CIN2+ was 89.80% in cervical scrape to 92.63% in self-collected vaginal samples.
The Negative Predictive Value (Negative Predictive Value) for cervical scrapes (85.7%) was higher than self-collected alternatives (P<0.001).
As for hrHPV and DNA Methylation, a perfect sensitivity (96.51%), Negative Predictive Value (90.00%) and Negative Likelihood Ratio(Negative Likelihood Ratio) (0.07) for CIN3+ were reached.
The prevalence of methylation for PAX1/ZNF671 genes exhibited a strong positive correlation with the severity of cervical lesions, and demonstrates a better diagnostic value for CIN2+ lesions.
DNA methylation testing, especially PAX1/ZNF671 offers a promising strategy to detect CIN2/3 lesions or more serious disease. Cervical samples were the perfect candidates for DNA methylation.
Furthermore, PAX1/ZNF671 methylation assays had a strong capacity in screening and excludingCIN2+ lesions among HPV-negative individuals.