BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-015048 on 15 June 2017. Downloaded from The Cost-Effectiveness of HPV-Based Cervical Cancer Screening in the Public Health System in Nicaragua ForJournal: peerBMJ Open review only Manuscript ID bmjopen-2016-015048 Article Type: Research Date Submitted by the Author: 04-Nov-2016 Complete List of Authors: Campos, Nicole; Harvard T.H. Chan School of Public Health, Health Policy and Management Mvundura, Mercy; PATH, Devices and Tools Program Jeronimo, Jose; PATH, Reproductive Global Health Program Holme, Francesca; PATH, Reproductive Health Global Program Vodicka, Elisabeth; University of Washington, School of Pharmacy Kim, Jane; Harvard School of Public Health, Health Policy and Management <b>Primary Subject Health economics Heading</b>: Global health, Health economics, Health policy, Obstetrics and Secondary Subject Heading: gynaecology, Public health Keywords: HEALTH ECONOMICS, Epidemiology < ONCOLOGY, PUBLIC HEALTH http://bmjopen.bmj.com/ on September 26, 2021 by guest. Protected copyright. For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 1 of 56 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-015048 on 15 June 2017. Downloaded from 1 2 3 1 The Cost-Effectiveness of HPV-Based Cervical Cancer Screening in the Public Health System in 4 5 2 Nicaragua 6 3 Nicole G. Campos, PhD, a Mercy Mvundura, PhD,b Jose Jeronimo, MD,c Francesca Holme, MPH,c Elisabeth 7 8 d a 9 4 Vodicka, MHA, Jane J. Kim, PhD 10 11 5 12 13 6 a Center for Health Decision Science, Harvard T.H. Chan School of Public Health, 718 Huntington Avenue, 14 15 For peer review only 16 7 Boston, Massachusetts, USA 17 18 8 b PATH, Devices and Tools Program, P.O. Box 900922, Seattle, Washington, USA 19 20 9 c PATH, Reproductive Health Global Program, P.O. Box 900922, Seattle, Washington, USA 21 22 d 23 10 University of Washington, School of Pharmacy, Seattle, Washington, USA 24 25 11 Corresponding author: Nicole G. Campos, 718 Huntington Avenue, Boston, MA 02115; e-mail: 26 27 12 [email protected]; phone: 617-432-2019; fax: 617-432-0190 28 29 30 13 Word count (abstract): 300 31 32 33 14 Word count (text): 4,068 http://bmjopen.bmj.com/ 34 35 36 15 37 38 16 39 40 41 on September 26, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 1 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 2 of 56 BMJ Open: first published as 10.1136/bmjopen-2016-015048 on 15 June 2017. Downloaded from 1 2 3 17 Abstract 4 5 18 Objectives: To evaluate the cost-effectiveness of HPV DNA testing (versus Pap-based screening) for 6 7 8 19 cervical cancer screening in Nicaragua. 9 10 20 Design: A previously developed Monte Carlo simulation model of the natural history of HPV infection 11 12 21 and cervical cancer was calibrated to epidemiologic data from Nicaragua. Cost data inputs were derived 13 14 22 using a micro-costing approach in Carazo, Chontales, and Chinandega departments; test performance 15 For peer review only 16 17 23 data were from a demonstration project in Masaya department. 18 19 24 Setting: Nicaragua’s public health sector facilities. 20 21 25 Participants: Women aged 30 to 59 years. 22 23 24 26 Interventions: Screening strategies included 1) Pap testing every 3 years, with referral to colposcopy for 25 26 27 women with an ASCUS+ result (“Pap”); 2) HPV testing every 5 years, with referral to cryotherapy for 27 28 28 HPV-positive eligible women (HPV screen-and-treat, or “HPV-ST”); 3) HPV testing every 5 years, with 29 30 31 29 referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women (“HPV-VIA”); and 32 33 30 4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women (“HPV-Pap”). http://bmjopen.bmj.com/ 34 35 31 Outcome measures: Reduction in lifetime risk of cancer; incremental cost-effectiveness ratios (ICER; 36 37 32 2015 US$ per year of life saved [YLS]). 38 39 40 33 Results: HPV-based screening strategies were more effective than Pap testing. HPV-ST was the least 41 on September 26, 2021 by guest. Protected copyright. 42 34 costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, 43 44 35 HPV-Pap, and Pap only, which reduced cancer risk by 19.4%, 12.2%, and 10.8%, respectively. With an 45 46 47 36 ICER of US$320/YLS, HPV-ST every 5 years would be very cost-effective using a threshold based on 48 49 37 Nicaragua’s per capita GDP of US$2,090. Findings were robust across sensitivity analyses on test 50 51 38 performance, coverage, compliance, and cost parameters. 52 53 54 55 56 57 58 59 60 2 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 3 of 56 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-015048 on 15 June 2017. Downloaded from 1 2 3 39 Conclusions: HPV testing is very cost-effective compared to Pap testing in Nicaragua, due to higher test 4 5 6 40 sensitivity and the relatively lower number of visits required. Increasing compliance with recommended 7 8 41 follow-up will further improve the health benefits and value for public health dollars. 9 10 42 11 12 13 14 15 For peer review only 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on September 26, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 4 of 56 BMJ Open: first published as 10.1136/bmjopen-2016-015048 on 15 June 2017. Downloaded from 1 2 3 43 Strengths and limitations of this study: 4 5 6 44 • Using implementation data from the Scale-Up project— which aims to facilitate 7 8 45 institutionalization of HPV testing at the national level in Guatemala, Honduras, and Nicaragua— 9 10 46 we estimated the cost-effectiveness of HPV testing in Nicaragua’s public health system. 11 12 13 47 • The screening algorithms, as modeled, reflect the prototypical structure of a screening episode 14 15 48 and the typeFor of facility peer at which visits usuallyreview take place, but doonly not capture variation due to 16 17 49 geography or health facility capacity. 18 19 20 50 • While we adopted a micro-costing approach to leverage data from implementation in 21 22 51 Nicaragua, individual-level data for each woman were not available; furthermore, we did not 23 24 52 have cost data associated with HPV self-collection in community settings, where most self- 25 26 27 53 collection takes place. 28 29 54 • Despite these limitations, extensive sensitivity analyses on cost and screening assumptions 30 31 55 indicate that HPV-ST is robustly the most efficient strategy. 32 33 http://bmjopen.bmj.com/ 56 34 35 36 57 Funding statement: This work was supported by the Bill & Melinda Gates Foundation. 37 38 39 58 Disclaimer: The findings and conclusions contained within are those of the authors and do not 40 41 on September 26, 2021 by guest. Protected copyright. 42 59 necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. The funders had no role 43 44 60 in study design; data collection, analysis, and interpretation; preparation of the manuscript; or decision 45 46 61 to submit the article for publication. 47 48 49 62 Competing interests disclosed: All authors have completed the ICMJE uniform disclosure form at 50 51 52 63 www.icmje.org/coi_disclosure.pdf and declare financial support from the Bill and Melinda Gates 53 54 64 Foundation for the submitted work; JJ was the director of the START-UP demonstration projects and 55 56 57 58 59 60 4 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml Page 5 of 56 BMJ Open BMJ Open: first published as 10.1136/bmjopen-2016-015048 on 15 June 2017. Downloaded from 1 2 3 65 received all tests used in the study as a donation from Qiagen; no other relationships or activities that 4 5 6 66 could appear to have influenced the submitted work. 7 8 67 Contributors: All authors developed the analysis plan and interpreted the data. NC, MM, JJ, FH, and JK 9 10 68 conceptualized the study. MM, JJ, FH, and EV collected implementation data. NC conducted data 11 12 13 69 analysis and wrote the first draft of the report and revised subsequent drafts. JJ was the principal 14 15 70 investigator of theFor START-UP andpeer Scale-Up projects. review JK was the principal only investigator overseeing 16 17 71 microsimulation model development. All authors contributed to and approved the final report. 18 19 72 Data sharing statement: A supplementary appendix is available. 20 21 22 23 24 25 26 27 28 29 30 31 32 33 http://bmjopen.bmj.com/ 34 35 36 37 38 39 40 41 on September 26, 2021 by guest. Protected copyright. 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 5 For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml BMJ Open Page 6 of 56 BMJ Open: first published as 10.1136/bmjopen-2016-015048 on 15 June 2017.