Clinical performance of high-risk HPV testing on self-samples versus clinician samples in routine primary HPV screening in the Netherlands: An observational study

Federica Inturrisi; Clare A Aitken; Willem J G Melchers; Adriaan J C van den Brule; Anco Molijn; John W J Hinrichs; Hubert G M Niesters; Albert G Siebers; Rob Schuurman; Daniëlle A M Heideman; Inge M C M de Kok; Ruud L M Bekkers; Folkert J van Kemenade; Johannes Berkhof

doi:10.1016/j.lanepe.2021.100235

Clinical performance of high-risk HPV testing on self-samples versus clinician samples in routine primary HPV screening in the Netherlands: An observational study

Lancet Reg Health Eur. 2021 Nov 9:11:100235. doi: 10.1016/j.lanepe.2021.100235. eCollection 2021 Dec.

Authors

Federica Inturrisi¹, Clare A Aitken^{2

3}, Willem J G Melchers⁴, Adriaan J C van den Brule⁵, Anco Molijn⁶, John W J Hinrichs⁷, Hubert G M Niesters⁸, Albert G Siebers⁹, Rob Schuurman¹⁰, Daniëlle A M Heideman¹¹, Inge M C M de Kok², Ruud L M Bekkers^{12

13}, Folkert J van Kemenade³, Johannes Berkhof¹

Affiliations

¹ Amsterdam UMC, Vrije Universiteit Amsterdam, Epidemiology and Data Science, Amsterdam Public Health, 1081 HV Amsterdam, Netherlands.
² Erasmus MC University Medical Center, Public Health, 3015 GD Rotterdam, Netherlands.
³ Erasmus MC University Medical Center, Pathology, 3015 GD Rotterdam, Netherlands.
⁴ Radboud University Medical Center, Medical Microbiology, 6525 GA Nijmegen, Netherlands.
⁵ Jeroen Bosch Hospital, Pathologie-DNA, 5223 GZ 's-Hertogenbosch, Netherlands.
⁶ NMDL-LCPL, 2280 CA Rijswijk, Netherlands.
⁷ Symbiant Pathology Expert Centre Hoorn, 1624 NP Hoorn, Netherlands.
⁸ University Medical Center Groningen, University of Groningen, Medical Microbiology, 9713 GZ Groningen, Netherlands.
⁹ PALGA, 3991 SZ Houten, Netherlands.
¹⁰ University Medical Center Utrecht, Medical Microbiology, 3584 CX Utrecht, Netherlands.
¹¹ Amsterdam UMC, Vrije Universiteit Amsterdam, Pathology, Cancer Center Amsterdam, 1081 HV Amsterdam, Netherlands.
¹² GROW School for Oncology and Developmental Biology, Maastricht University, 6229 ER Maastricht, Netherlands.
¹³ Catharina Hospital, 5623 EJ Eindhoven, Netherlands.

Abstract

Background: High-risk human papillomavirus (hrHPV) testing on self-collected samples has potential as a primary screening tool in cervical screening, but real-world evidence on its accuracy in hrHPV-based screening programmes is lacking.

Methods: In the Netherlands, women aged 30-60 years invited for cervical screening can choose between sampling at the clinician's office (Cervex Brush) or self-sampling at home (Evalyn Brush). HrHPV testing is performed using Roche Cobas 4800. We collected screening test results between January 2017 and March 2018 and histological follow-up until August 2019. The main outcome measures were mean cycle threshold (Ct) value, cervical intraepithelial neoplasia (CIN) grade 3 or cancer (CIN3+) and CIN grade 2 or worse (CIN2+).

Findings: 30,808 women had a self-collected and 456,207 had a clinician-collected sample. In hrHPV-positive women with adequate cytology, Ct values were higher for self-collection than clinician-collection with a mean Ct difference of 1·25 (95% CI 0·98-1·52) in women without CIN2+, 2·73 (1·75-3·72) in CIN2 and 3·59 (3·03-4·15) in CIN3+. The relative sensitivity for detecting CIN3+ was 0·94 (0·90-0·97) for self-collection versus clinician-collection and the relative specificity was 1·02 (1·02-1·02).

Interpretation: The clinical accuracy of hrHPV testing on a self-collected sample for detection of CIN3+ is high and supports its use as a primary screening test for all invited women. Because of the slightly lower sensitivity of hrHPV testing on a self-collected compared to a clinician-collected sample, an evaluation of the workflow procedure to optimise clinical performance seems warranted.

Funding: National Institute for Public Health and the Environment (the Netherlands) and the European Commission.

Keywords: CIN3; Cervical intraepithelial neoplasia; Cervical screening; Clinical accuracy; Human papillomavirus (HPV); Routine screening; Self-sampling.