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.

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.

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

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.

Defining Optimal Triage Strategies for hrHPV Screen-Positive Women-An Evaluation of HPV 16/18 Genotyping, Cytology, and p16/Ki-67 Cytoimmunochemistry.

Background: Several options for the triage of high-risk HPV screen-positive (hrHPV+) women were assessed.Methods: 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.Results: 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.Conclusions: 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.Impact: 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%. Cancer Epidemiol Biomarkers Prev; 26(11); 1629-35. ©2017 AACR.