Te Ara Waiora–Implementing human papillomavirus (HPV) primary testing to prevent cervical cancer in Aotearoa New Zealand: A protocol for a non-inferiority trial

PLOS ONE STUDY PROTOCOL Te Ara Waiora–Implementing human papillomavirus (HPV) primary testing to prevent cervical cancer in Aotearoa New Zealand: A protocol for a non-inferiority trial a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Gibson-Helm M, Slater T, MacDonald EJ, Stevenson K, Adcock A, Geller S, et al. (2023) Te Ara Waiora–Implementing human papillomavirus (HPV) primary testing to prevent cervical cancer in Aotearoa New Zealand: A protocol for a noninferiority trial. PLoS ONE 18(3): e0280643. https:// doi.org/10.1371/journal.pone.0280643 Editor: James Mockridge, PLOS: Public Library of Science, UNITED KINGDOM Received: December 5, 2022 Accepted: December 7, 2022 Published: March 23, 2023 Copyright: © 2023 Gibson-Helm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All named investigators will have access to the final trial dataset. This research aligns with Te Mana Raraunga Principles of Māori Data Sovereignty, which strictly govern Māori data use and sharing. Data requests with evidence that the proposed use addresses and upholds these principles may be sent to Te Ara Waiora Data Management Committee at for consideration by the project’s data management and steering committees. Melanie Gibson-Helm1, Tania Slater1, Evelyn J. MacDonald1, Kendall Stevenson1, Anna Adcock1, Stacie Geller2, Varsha Parag3, Charles Lambert1, Matthew Bennett1, Merilyn Hibma4, Peter Sykes5, Marion Saville6, David Hawkes6, Jo-Ann Stanton1, MaryAnn Clueard7, Grahame Jelley7, Bev Lawton1* 1 Te Tātai Hauora o Hine–National Centre for Women’s Health Research Aotearoa (NCWHRA), Victoria University of Wellington, Wellington, New Zealand, 2 National Center of Excellence in Women’s Health, University of Illinois, Chicago, IL, United States of America, 3 National Institute for Health Innovation, University of Auckland, Auckland, New Zealand, 4 Department of Pathology, University of Otago, Dunedin, New Zealand, 5 Christchurch Hospital and University of Otago, Canterbury, New Zealand, 6 Australian Centre for the Prevention of Cervical Cancer, Melbourne, Australia, 7 Mahitahi Hauora Primary Health Entity, Northland, New Zealand * Abstract Background Cervical cancer is caused by high-risk types of human papillomavirus (HPV). Testing for high-risk HPV is a more sensitive screening method than cervical cytology for detecting cervical changes that may lead to cancer. Consistent with recent evidence of efficacy and acceptability, Aotearoa New Zealand plans to introduce HPV testing as the primary approach to screening, replacing cervical cytology, from mid-2023. Any equitable cervical screening programme must be effective across a diverse population, including women that the current programme fails to reach, particularly Māori and those in rural areas. Currently, we do not know the best model for implementing an equitable HPV self-testing screening programme. Methods This implementation trial aims to assess whether a universal offer of HPV self-testing (offered to all people eligible for cervical screening) achieves non-inferior screening coverage (equal) to a universal offer of cervical cytology alone (the present programme). The study population is all people aged from 24.5 to 70 years due for cervical screening in a 12month period (including those whose screening is overdue or who have never had screening). A range of quantitative and qualitative secondary outcomes will be explored, including barriers and facilitators across screening and diagnostic pathways. This study takes place in Te Tai Tokerau/Northland which covers a diverse range of urban and rural areas and has a large Indigenous Māori population. A total of fourteen practices will be involved. Seven PLOS ONE | https://doi.org/10.1371/journal.pone.0280643 March 23, 2023 1 / 19 PLOS ONE Te Ara Waiora – Implementing HPV self-testing in Aotearoa New Zealand Funding: This project received funding from The Health Research Council of New Zealand: Health Delivery Research Project Grant 20/960, The Ministry of Health – Manatū Hauora, New Zealand, and Mahitahi Hauora Primary Health Entity. The study sponsor (Victoria University of Wellington), the Health Research Council of New Zealand, and the Ministry of Health – Manatū Hauora, have no role in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication. Mahitahi Hauora fund a proportion of the laboratory tests. Two co-investigators from Mahitahi Hauora (M-AC and GJ) contributed to adapting the study database canSCREEN® and operational management of the study and will contribute to writing of the report. Neither the study sponsor nor any of the funders have ultimate authority over any of the above-mentioned activities. practices will offer HPV self-testing universally to approximately 2800 women and will be compared to seven practices providing routine clinical care (offer of cervical cytology) to an approximately equal number of women. Competing interests: Co-investigators are clinicians with clinical responsibility for participants. This is acknowledged by the research team as potential for conflict of interest. However, the dual role of clinician being also researcher in this study would appear to be appropriate as the participant will have her usual clinician providing care, advice and follow up. This will be fully disclosed and discussed with the participants. Coinvestigators are not remunerated for recruiting participants to the study. Introduction Abbreviations: ACPCC, Australian Centre for the Prevention of Cervical Cancer; CIN, Cervical intraepithelial neoplasia; DMC, Data management committee; HDEC, Health and Disability Ethics Committee; HPV, Human papillomavirus; NCSP, National Cervical Screening Programme; NCWHRA, National Centre for Women’s Health Research Aotearoa; NHI, National Health Index; NIR, National Immunisation Register; NSU, National Screening Unit; PHE, Primary Health Entity; PHO, Primary Health Organisation. Discussion This trial will answer important questions about how to implement an equitable, high-quality, effective national programme offering HPV self-testing as the primary screening method for cervical cancer prevention. Trial registration Prospectively registered with the Australian New Zealand Clinical Trials Registry 07/12/ 2021: ACTRN12621001675819. Background and rationale Cervical cancer is now preventable by vaccination and screening [1]. Screening can detect precancerous lesions that can be treated, thereby preventing the development of potentially fatal disease. Cervical cancer is caused by high-risk types of human papillomavirus (HPV). It is globally recognised that testing for high-risk HPV is (...truncated)