Women who test high-risk human papillomavirus (hrHPV)-positive require triage to identify those with cervical high-grade intraepithelial neoplasia and cancer (≥CIN3). FAM19A4 methylation analysis, a promising triage marker which detects advanced CIN and cancer, is applicable to different sample types. However, studies comparing the performance of FAM19A4 methylation analysis in hrHPV-positive self-samples and paired physician-taken scrapes are lacking.
We compared the performance of FAM19A4 methylation analysis (with or without HPV16/18 genotyping) in self-collected lavages and paired physician-taken scrapes for ≥CIN3 detection in hrHPV-positive women (n=450, 18-66 years) visiting gynecologic outpatient clinics.
In women ≥30 years, ≥CIN3 sensitivity of FAM19A4 methylation analysis was 78.4% in lavages and 88.2% in scrapes (ratio 0.89, CI:0.75-1.05). In women <30 years, ≥CIN3 sensitivities were 37.5% and 45.8%, respectively (ratio 0.82, CI:0.55-1.21). In both age groups, ≥CIN3 specificity of FAM19A4 methylation analysis was significantly higher in lavages compared to scrapes (≥30 years:73.1% versus 63.2%; ratio 1.16, CI:1.03-1.30; <30 years:90.8% versus 82.2%; ratio 1.10, CI:1.02-1.20). In contrast to FAM19A4 methylation analysis alone, the performance of combined FAM19A4 methylation analysis and HPV16/18 genotyping did not differ significantly between lavages and scrapes.
FAM19A4 methylation analysis in hrHPV-positive self-collected lavages had a slightly lower sensitivity and a higher specificity for ≥CIN3 detection compared to FAM19A4 methylation analysis in paired physician-taken scrapes. Combined FAM19A4 methylation analysis and HPV16/18 genotyping revealed a similarly good clinical performance in both sample types. Therefore, this combination provides a feasible triage strategy for hrHPV-positive women, with the advantage of direct applicability on self-collected material.