Several options for the triage of high-risk HPV screen-positive (hrHPV) women were assessed. This study incorporated CIN2 cases and controls, all of whom tested hrHPV and whose results of liquid-based cytology (LBC), HPV16/18 genotyping, and p16/Ki67 cytoimmunochemistry were available. Sensitivity and specificity for the CIN2 of these triage tests were evaluated. Absolute sensitivities of HPV 16/18 typing, LBC, and p16/Ki-67 cytoimmunochemistry for CIN2 detection were 61.7%, 68.3%, and 85.0% for women with hrHPV clinician-taken samples. Respective specificities were 70.5%, 89.1%, and 76.7%. The absolute accuracy of the triage tests was similar for women with a hrHPV self-sample. P16/Ki-67 cyto-immunochemistry was significantly more sensitive than LBC although significantly less specific. All three single-test triage options, if positive, exceed the threshold of 20% risk at which colposcopy would be indicated. However, none of them conferred a post-test probability of CIN2 <2%; which would permit routine recall. P16/Ki-67 cytoimmunochemistry on HPV16/18 negative women had a post-test probability of CIN2 of 1.7% and 0.6% if also LBC negative. This is one of the few studies to directly compare the performance of triage strategies of hrHPV women, in isolation and combinations. It is the only study assessing triage strategies in women who test hrHPV in self-taken vaginal samples. A combined triage option that incorporated HPV 16/18 typing prior to p16/ki-67 cytoimmunochemistry in HPV 16/18-negative women yielded a post-test probability of CIN2 of >20%, whereas women who tested negative had a probability of CIN2 of <2%. .

Self‐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.

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 Hr-HPV positive (Hr-HPV+) women within the cervical screening programme 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 three years (in women &lt;50 years) or five years (in women &gt; 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 (&gt;= 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 prior to LBC (or DS) for Hr-HPV Other+ for Hr-HPV Other + women were associated with a lower risk of significant disease at follow up compared to 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.