Comparative Assessment of p16/Ki-67 Dual Staining Technology for cervical cancer screening in women living with HIV (COMPASS-DUST)–Study protocol

PLOS ONE STUDY PROTOCOL Comparative Assessment of p16/Ki-67 Dual Staining Technology for cervical cancer screening in women living with HIV (COMPASS-DUST)–Study protocol a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Okunade KS, Badmos KB, Okoro AC, Ademuyiwa IY, Oshodi YA, Adejimi AA, et al. (2023) Comparative Assessment of p16/Ki-67 Dual Staining Technology for cervical cancer screening in women living with HIV (COMPASS-DUST)– Study protocol. PLoS ONE 18(1): e0278077. https://doi.org/10.1371/journal.pone.0278077 Editor: Richard Ali, UNITED KINGDOM Received: December 10, 2022 Accepted: January 10, 2023 Published: January 26, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0278077 Copyright: © 2023 Okunade 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: No datasets were generated or analysed during the current study. All relevant data from this study will be made available upon study completion. Kehinde S. Okunade ID1,2,3*, Kabir B. Badmos4, Austin C. Okoro2, Iyabo Y. Ademuyiwa5, Yusuf A. Oshodi6, Adebola A. Adejimi7, Nicholas A. Awolola4, Oluchi Ozonu2, Hameed Adelabu ID3, Gbenga Olorunfemi8, Alani S. Akanmu ID9, Adekunbiola A. Banjo4, Rose I. Anorlu1,2, Jonathan S. Berek10 1 Department of Obstetrics & Gynaecology, College of Medicine, University of Lagos, Lagos, Nigeria, 2 Department of Obstetrics & Gynaecology, Lagos University Teaching Hospital, Lagos, Nigeria, 3 Center for Clinical Trial, Research, and Implementation science (CCTRIS), College of Medicine, University of Lagos, Lagos, Nigeria, 4 Department of Anatomic and Molecular Pathology, College of Medicine, University of Lagos, Lagos, Nigeria, 5 Department of Nursing Science, College of Medicine, University of Lagos, Lagos, Nigeria, 6 Department of Obstetrics & Gynaecology, Lagos State University College of Medicine, Lagos, Nigeria, 7 Department of Community Health & Primary Care, College of Medicine, University of Lagos, Lagos, Nigeria, 8 Division of Epidemiology and Biostatistics, School of Public Health, University of Witwatersrand, Johannesburg, South Africa, 9 Department of Haematology & Blood Transfusion, College of Medicine, University of Lagos, Lagos, Nigeria, 10 Department of Obstetrics & Gynaecology, Stanford University School of Medicine, Stanford, United States of America * Abstract The risk of progression of low-grade (CIN1) to high-grade cervical intraepithelial neoplasia (CIN2/3) is 3–5 times higher for women living with HIV (WLHIV) than for HIV-negative women. Evidence suggests that the current cervical cancer screening methods perform less effectively in WLHIV. An emerging screening method–p16/Ki-67 dual staining technology (DUST) is a safe and rapid assay that could be used to detect CIN2/3 with higher sensitivity and specificity. The study in this protocol will evaluate the performance of DUST in cervical cancer screening among WLHIV. We will conduct an intra-participant comparative study (Phase 1) to enrol n = 1,123 sexually active WLHIV aged 25–65 years at two accredited adult HIV treatment centres in Lagos, Nigeria to compare the performance of DUST to the currently used screening methods (Pap smear, hr-HPV DNA, or VIA testing) in detecting high-grade CIN and cancer (CIN2+). Subsequently, a prospective cohort study (Phase 2) will be conducted by enrolling all the WLHIV who are diagnosed as having low-grade CIN (CIN1) in Phase 1 for a 6-monthly follow-up for 2 years to detect the persistence and progression of CIN1 to CIN2+. The findings of this study may provide evidence of the existence of a better performance screening method for the primary and triage detection of CIN2+ in WLHIV. It may also demonstrate that this high-performance test can improve the long-term predictive accuracy of screening by extending the intervals between evaluations and thus decrease the overall cost and increase screening uptake and follow-up compliance in WLHIV. PLOS ONE | https://doi.org/10.1371/journal.pone.0278077 January 26, 2023 1/9 PLOS ONE Funding: The lead author (KSO) received support for the research proposed in this publication from the National Cancer Institute and Fogarty International Center of the National Institutes of Health under Award Number K43TW011930. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, Fogarty International Center, or the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: KSO and GO are both editorial board members of PLoS One. This does not alter our adherence to PLOS ONE policies on sharing data and materials. p16/Ki-67 dual staining technology for cervical cancer screening—Protocol Introduction Cervical cancer is a major public health problem and is the fourth leading cause of cancer death in women worldwide accounting for an estimated 604,000 new cases and 342,000 deaths in 2020 [1]. In Nigeria, the annual number of cervical cancer cases is 14,089 and the number of deaths is 8,240 [2]. Invasive cervical cancer (ICC) is regarded as an AIDS-defining illness [3]. Sub-Saharan Africa is the region most affected by the global human immunodeficiency virus (HIV) epidemic with an estimated 25 million cases [4] accounting for about 80% of the global burden of ICC [1]. Persistent infection with genital high-risk human papillomavirus (hr-HPV) is a necessary cause of ICC [5] and therefore, women living with HIV (WLHIV), who are disproportionately affected by HPV infection [6, 7] are also more likely to have persistent HPV infections and a more rapid progression to ICC [7]. Nigeria currently ranks second, behind South Africa, in the global burden of HIV [8]. The increased coverage of antiretroviral treatment (ART) leading to the improved life expectancy of WLHIV together with the poor screening and follow-up have contributed significantly to the high prevalence and incidence of ICC in Nigeria and other low- and middle-income countries (LMICs) [9]. Integrated cervical cancer screening is now used in most settings including Nigeria as an effective measure to reduce the morbidity and mortality due to ICC in WLHIV [10]. The World Health Organization (WHO) recommends HPV DNA-based test as the preferred method to d (...truncated)