Grazyna A. Stanczuk

Self‐sampling as the principal modality for population based cervical screening: Five‐year follow‐up of the PaVDaG study

AbstractSelf‐sampling provides a powerful means to engage women in cervical screening. In the original Papillomavirus Dumfries and Galloway study (PaVDaG), we demonstrated cross‐sectional similarity of high‐risk human papillomavirus (Hr‐HPV) testing on self‐taken vaginal vs clinician‐taken samples for the detection of cervical intraepithelial neoplasia 2 or worse (CIN2+). Few data exist on the longitudinal performance of self‐sampling; we present longitudinal outcomes of PaVDaG. Routinely screened women provided a self‐taken and a clinician‐collected sample. Ninety‐one percent of 5136 women from the original cohort completed a further screening round. Sensitivity, specificity, positive predictive value and complement of the negative predictive value of the Hr‐HPV test on self‐samples for detection of CIN2+ and CIN3+ up‐to 5 years after testing were determined. Additionally, clinical accuracy of Hr‐HPV testing on vaginal and clinician‐collected samples was assessed. A total of 183 CIN2+ and 102 CIN3+ lesions were diagnosed during follow‐up. Risk of CIN2+ and CIN3+ following an Hr‐HPV negative self‐sample was 0.6% and 0.2%, respectively, for up to 5 years after testing. The relative sensitivity for CIN3+ and specificity for ≤CIN1 of Hr‐HPV testing on self‐taken specimens was slightly lower vs clinician‐collected samples: 0.95 (95% CI: 0.90‐0.99; PMcN = .0625) and 0.98 (95% CI: 0.95‐1.00; PMcN = <.0000), respectively. The low risk of CIN2+ in women with Hr‐HPV—self‐sample(s) suggests, that the 3 to 5‐year recall interval implemented in several cervical screening settings, based on clinician‐taken samples, may be safe for self‐samples. Future assessment will show if “universal” 5‐year screening is appropriate for programs based on self‐sampling.

Clinical Performance of Triage Strategies for Hr-HPV–Positive Women; A Longitudinal Evaluation of Cytology, p16/K-67 Dual Stain Cytology, and HPV16/18 Genotyping

Abstract Background: We evaluated the longitudinal performance of three options: HPV16/18 genotyping (HPV16/18), cytology (LBC), and p16/Ki-67 dual stain cytology (DS) for the triage of high-risk Human Papillomavirus–positive (Hr-HPV+) women within the cervical screening program in Scotland. Methods: Data were derived from a cohort of Hr-HPV+ women (n = 385) who participated in PaVDaG (Papillomavirus Dumfries and Galloway) study. Performance of triage strategies for detecting high-grade disease was assessed at 3 (in women <50 years) or 5 years (in women >50 years). Sensitivity, specificity, PPV, and cNPV of each triage test were calculated for CIN2+ and CIN3+ when used singly or sequentially. Results: The sensitivity of LBC (≥ borderline), DS, and HPV 16/18 genotyping for the detection of CIN2+ was 62.7% (50.7–73.3), 77.7% (63.1–83.7), and 62.7% (50.7–73.3) with corresponding cNPVs of 10.9%, 8.4%, and 11.9%. The option with the highest sensitivity and lowest cNPV was HPV 16/18 genotyping followed by LBC of Hr-HPV other+ and then DS of the LBC negatives. This yielded sensitivity of 94.7% (86.2–98.3) and cNPV 2.7% for CIN2+. Triage performance was similar if women had tested Hr-HPV+ positive by vaginal self-sampling. Conclusions: Two-step triage with HPV 16/18 genotyping before LBC (or DS) for Hr-HPV other+ women was associated with a lower risk of significant disease at follow-up compared with single triage approaches. Impact: This study provides longitudinal performance data on triage strategies in Hr-HPV+ women and will be informative for the evolution of cervical screening programs that increasingly rely on molecular technologies.