DNA methylation testing with S5 for triage of high-risk HPV positive women
Menée aux Etats-Unis à partir d'échantillons cytologiques cervicaux provenant de femmes infectées par un papillomavirus humain à haut risque, cette étude évalue la performance d'un système de score, basé sur le niveau de méthylation du gène humain EPB41L3 et des gènes tardifs L1 et L2 des virus de type 16, 18, 31 ou 33, pour identifier les patientes nécessitant une colposcopie et déterminer le grade des lésions cervicales intra-épithéliales
Methylation testing of host and viral genes is promising for triage of women with high-risk human papillomavirus infections (hrHPV). Using a population-based sample of hrHPV positive women with cervical biopsies within 12 months after routine cervical screening, the clinical value of the S5 methylation classifier (S5), HPV genotyping and cytology were compared as potential triage tests, for outcomes of cervical intraepithelial neoplasia (CIN) grade 3 or greater (CIN3+), CIN2+ and CIN2, and the area under the curve (AUC) calculated.
S5 methylation scores increased with histopathology severity (Ptrend<0.001). For CIN3+, the AUC was 0.780 suggesting S5 provides good discrimination between <CIN3 and CIN3+. AUCs were significant for all pairwise comparisons of <CIN2, CIN2 and CIN3+ (P<0.001). The positive predictive value (PPV) of HPV16/18 genotyping was greater than S5 methylation (25.36% vs 20.87%, P=0.005) for CIN3+, while sensitivity was substantially greater for S5 (83.33% vs 59.28%, P<0.001). Restricting to women with abnormal cytology, but excluding those with high-grade cytology, both S5 and HPV16/18 provided CIN3+ PPVs high enough to recommend colposcopy. Triage with S5 also appeared useful for hrHPV positive women negative for HPV16/18 (CIN3+ PPV: 7.33%, sensitivity: 57.52%).
S5 provided increased sensitivity for CIN3+ compared to HPV16/18 genotyping for hrHPV positive women, both overall and when restricted to women with abnormal cytology, suggesting S5 may improve colposcopy referral selection. S5 also has the ability to distinguish between <CIN2, CIN2 and CIN3+, a finding of importance for managing CIN2, given the complexity and uncertainty associated with this diagnosis.
International Journal of Cancer , article en libre accès, 2021