Alexandra Sargent

Widening the offer of human papillomavirus self‐sampling to all women eligible for cervical screening: Make haste slowly

AbstractSelf‐collection of samples for human papillomavirus (HPV) testing has the potential to increase the uptake of cervical screening among underscreened women and will likely form a crucial part of the WHO's strategy to eliminate cervical cancer by 2030. In high‐income countries with long‐standing, organised cervical screening programmes, self‐collection is increasingly becoming available as a routine offer for women regardless of their screening histories, including under‐ and well‐screened women. For these contexts, a validated microsimulation model determined that adding self‐collection to clinician collection is likely to be cost‐effective on the condition that it meets specific thresholds relating to (1) uptake and (2) sensitivity for the detection of high‐grade cervical intraepithelial neoplasia (CIN2+). We used these thresholds to review the ‘early‐adopter’ programme‐level evidence with a mind to determine how well and how consistently they were being met. The available evidence suggested some risk to overall programme performance in the situation where low uptake among underscreened women was accompanied by a high rate of substituting clinician sampling with self‐collection among well‐screened women. Risk was further compounded in a situation where the slightly reduced sensitivity of self‐sampling vs clinician sampling for the detection of CIN2+ was accompanied with lack of adherence to a follow‐up triage test that required a clinician sample. To support real‐world programmes on their pathways toward implementation and to avoid HPV self‐collection being introduced as a screening measure in good faith but with counterproductive consequences, we conclude by identifying a range of mitigations and areas worthy of research prioritisation.

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

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.