Journal Article

Staged design recommendations for validating relative sensitivity of self-sample human papillomavirus tests for cervical screening

Brentnall, Adam R., Berkhof, Johannes, Cuschieri, Kate, Rebolj, Matejka, Sargent, Alexandra

2024

Overview

To ensure that the emerging methods for human papillomavirus (HPV) testing on self-collected samples in cervical screening are evaluated robustly. We assess paired study designs for relative sensitivity of self-collected vs. traditional clinician-collected samples in detection of high-grade cervical intraepithelial neoplasia. 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. A universal recommendation for an optimal study design is challenging. Staged validation might be useful with D5 as a gatekeeper for D1-D4. •It is important to understand self-collected human papillomavirus (HPV) test sensitivity.•Most studies done previously in the field are at risk of spectrum bias.•Currently no consensus study design guidelines, unlike for clinician-collected HPV assays.•Paired designs to estimate relative sensitivity of self-collection tests are reviewed.•A flexible, staged, adaptive design for evaluation is recommended.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Accuracy / Bias / Cervical cancer / Design / Early Detection of Cancer - methods / Female / HPV / Human papillomavirus / Human Papillomavirus Viruses / Humans / Internal Medicine / Mass Screening - methods / Medical screening / Papillomaviridae / Papillomavirus Infections - diagnosis / Sampling / Screening / Self-sampling / Sensitivity and Specificity / Standard of care / Study design / Uterine Cervical Neoplasms - diagnosis / Validation / Women