92 Chapter 4 To date, most studies have been performed in cohorts of under-screened or neverscreened women and referral populations. The current study aimed to assess the triage performance of host-cell methylation analysis on hrHPV-positive self-collected samples within the context of routine HPV-based screening. For this, we used self-collected samples of hrHPV-positive women participating in the IMPROVE study, a primary HPV self-sampling trial carried out within the organised population-based screening program in the Netherlands 5. The IMPROVE study cohort enabled us to compare methylation data between self-collected samples and paired clinician-collected cervical samples and cervical tissue specimens from the same hrHPV-positive women. We evaluated the methylation markers ASCL1 and LHX8 that were discovered in self-collected samples 19 and previously evaluated for clinical performance on clinician-collected cervical samples 24, 25 and self-collected samples from screening non-attendees 19. METHODS CLINICAL SPECIMENS This is a post hoc analysis of the IMPROVE study (Netherlands Trial Register, number NTR5078), a randomised non-inferiority trial, that was performed to evaluate the clinical accuracy of HPV testing on self-collected samples and clinician-collected samples within the setting of the Dutch cervical cancer screening program. A detailed description of the IMPROVE trial has been previously published 5. In brief, 16,410 women were enrolled and randomised (1:1) to the intervention group (self-sampling) or the control group (clinicianbased sampling). Consistent with the randomised, paired screen-positive design, hrHPV-positive women (n = 1,020) were retested using the other collection method. In accordance with the current guidelines of the Dutch primary HPV screening program, women with a positive HPV test result were triaged by cytology. HrHPV-positive women with baseline borderline or mild dyskaryosis (BMD) or worse (≥BMD) as per CISOE-A classification equal to atypical squamous cells of undetermined significance (ASC-US or worse; ≥ASC-US) in the Bethesda classification 26, were immediately referred to a gynaecologist for colposcopy. HrHPV-positive women with normal cytology (i.e., negative for intraepithelial lesion or malignancy [NILM]) at baseline were advised to undergo repeat cytological testing after 6 months and were referred for colposcopy when repeat cytology was ≥BMD. Women with two consecutive normal cytology results (also referred to as 2x NILM) were referred to the next routine screening round at a five-year interval. For this study, we used self-collected samples from hrHPV-positive women, who either
RkJQdWJsaXNoZXIy MjY0ODMw