Objectives: To ensure that the emerging methods for human papillomavirus (HPV) testing on self-collected samples in cervical screening are evaluated robustly.
Study Design and Setting: We assess paired study designs for relative sensitivity of self-collected vs. traditional clinician-collected samples in detection of high-grade cervical intraepithelial neoplasia.
Results: Designs considered are (D1) both samples at screening, with clinical actions triggered by HPV positivity; (D2) offering a self-sample test to clinician-collected HPV-positive women; (D3) as D2 but using a repeat clinician-sample as comparator; (D4) offering a choice of self- vs. clinician-sampling, and the alternative test in HPV-positive women; (D5) paired samples at referral appointment. D1 is simple to analyze but requires the largest sample size and referral of self-sample positive, clinician-sample negative women. D2 requires a much smaller sample size, and no change to clinical practice, and could be used to rule-in a test because estimates are conservative (against self-sampling). D3 mitigates this bias but requires a second clinician sample. D4 is only manageable where self-sampling already occurs. The liberal D5 might be used to rule-out a self-sampling test.
Conclusion: A universal recommendation for an optimal study design is challenging. Staged validation might be useful with D5 as a gatekeeper for D1-D4.
Competing Interests: Declaration of competing interest AB is member of the UK National Screening Committee Research and Methodology subgroup. KC reports research funding or consumables to support research in the last 3 years from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis Seegene, Roche, Abbott and Hologic, paid to employer. Professional Clinical Advisor to the English Cervical Screening Programme; member of various expert groups providing advice to the English Cervical Screening Programme including on HPV self-sampling; member of the working group that has provided advice to the Scottish Cervical Screening Programme on the potential use of HPV self-sampling within the program. AS is member of various expert groups providing advice to the English Cervical Screening Programme including on HPV self-sampling; holds an honorary contract with The University of Manchester to support research into HPV testing in urine samples and Professional Clinical Advisor to the English Cervical Screening Programme. JB reports grants with income to institution from the Dutch National Institute for Public Health and the Environment. (Rijksinstituut voor Volksgezondheid en Milieu, RIVM). MR reports previous research funding received to instution from the former Public Health England (now: NHS England and Department of Health/Office for Health Improvement and Disparities) for epidemiological evaluation of various cervical screening studies; member of various expert groups providing advice to the English Cervical Screening Programme; attended meetings with HPV test manufacturers; fees for attendance at advisory board and other meetings by Hologic, shared with employer.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)