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Early Evidence of the Effectiveness of the Human Papillomavirus Vaccination Program Against Anogenital Warts in Manitoba, Canada: A Registry Cohort Study

Willows, Karla, MD, FRCS*; Bozat-Emre, Songul, PhD*†‡; Righolt, Christiaan, H., PhD; Kliewer, Erich, V., PhD; Mahmud, Salaheddin, M., MD, PhD, FRCP*†‡

Sexually Transmitted Diseases: April 2018 - Volume 45 - Issue 4 - p 254–259
doi: 10.1097/OLQ.0000000000000742
Original Studies

Background We assessed the effectiveness of the quadrivalent human papillomavirus vaccine (qHPV) vaccination program in Manitoba, Canada, in reducing incident anogenital warts (AGWs) and to what extent effectiveness depends on age at vaccination and number of doses.

Methods Female participants 9 years or older who received the qHPV in Manitoba between September 2006 and March 2013 (n = 31,464) through the publicly funded school-based program and a high-risk catch-up program were included. They were matched on age and area of residence to unvaccinated female participants. Information on incident AGWs was obtained from provincial administrative databases using validated algorithms. Using stratified Cox regression models, we estimate hazard ratios (HRs) for the association between qHPV and AGWs.

Results For female participants vaccinated at age 18 years or younger, receipt of qHPV was associated with a 40% reduction in AGW risk (HR, 0.6; 95% confidence interval [CI], 0.4–0.8). Further adjustment for socioeconomic and medical history did not alter this estimate. For women vaccinated at age 19 years or older, we saw an increase in AGW incidence, especially among those who were sexually active (HR, 2.8; 95% CI, 2.1–3.7). Among female participants vaccinated at age 18 years or younger, risk of AGWs was lowest among those who received 3 doses, corresponding to a vaccine effectiveness of 56% (95% CI, 30%–70%). For women vaccinated at older age, risk of AGWs remained increased regardless of the number of doses.

Conclusions Women vaccinated at an older (≥19 years) age may be less protected against AGWs, particularly if sexually active before vaccine administration. Further efforts should be targeted at increasing vaccine uptake among preadolescents before the initiation of sexual activity.

The risk of anogenital warts was reduced by 40% among girls vaccinated when they were younger than 18 years. No reduction in risk was found among women vaccinated at an older age.

From the *Department of Community Health Sciences, Rady Faculty of Health Sciences, and †Vaccine and Drug Evaluation Centre, Community Health Sciences, University of Manitoba, Winnipeg; ‡Manitoba Health, Seniors and Active Living, Epidemiology and Surveillance Unit, Government of Manitoba, Winnipeg, Manitoba; and §Cancer Control Research, British Columbia Cancer Agency, Vancouver, British Columbia, Canada

Acknowledgments: The authors acknowledge the Manitoba Centre for Health Policy for use of data contained in the Population Health Research Data Repository under project no. 2015-019 (HIPC No. 2014/2015-46; REB No. HS18467 [H2015:026]; RRIC No. 2015-060).

Funding support: This work was supported by an unrestricted grant from Merck Canada Inc to the International Centre of Infectious Disease (Winnipeg, Canada). The sponsor had no role in the design or conduct of the study, including but not limited to data identification, collection, management, analysis and interpretation, or preparation, review, or approval of the final results. The opinions presented in the report do not necessarily reflect those of the funders. S.M.M. was supported by an establishment grant from the Manitoba Health Research Council. S.M.M. is a Canada Research Chair in Pharmaco-epidemiology and Vaccine Evaluation and the Great-West Life, London Life, and Canada Life Junior Investigator of the Canadian Cancer Society (Grant No. 2011-700644). None of the funders had any role in the design and conduct of the study, analysis and interpretation of the data, or preparation or approval of the manuscript.

Conflict of Interest and Source of Funding: S.M.M. has received unrestricted research grants from GlaxoSmithKline, Sanofi Pasteur, and Pfizer for unrelated studies. E.V.K. has received consulting fees from Merck Canada and GlaxoSmithKline for unrelated studies. Also, he has received honoraria and travel expenses from Merck Canada. None of the other authors have any conflicts of interest that could affect the design or analysis of this project.

Transparency declaration: The senior author and the article's guarantor (S.M.M.) affirms that the article is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been explained.

Data sharing: The analysis data set for this study can be directly requested from the data custodians (Manitoba Health, Seniors and Active Living, and Manitoba Centre for Health Policy).

Authors' contribution: S.M.M. designed the study and supervised the analysis. E.K. contributed to the conception and design of the study and to the interpretation of the data. C.H.R. contributed to the interpretation of the data. K.W., S.B.E., and S.M.M. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. K.W. and S.B.E. analyzed the data. K.W., C.H.R., and S.M.M. drafted the manuscript. All authors critically revised the manuscript for intellectual content and approved the final draft for submission.

Patient involvement: Patients were not involved in the development of the research question, study design, or conduct.

Disclaimers: The results and conclusions are those of the authors, and no official endorsement by the Manitoba Centre for Health Policy, Manitoba Health, or other data providers is intended or should be inferred. Data used in this study are from the Population Health Research Data Repository housed at the Manitoba Centre for Health Policy, University of Manitoba, and were derived from data provided by Manitoba Health, CancerCare Manitoba, and the Winnipeg Regional Health Authority.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Correspondence: Salaheddin M. Mahmud, MD, PhD, FRCPC, Department of Community Health Sciences, University of Manitoba, 339-750 McDermot Ave, Winnipeg, Manitoba, Canada R3E 0T5. E-mail:

Received for publication June 14, 2017, and accepted September 23, 2017.

© Copyright 2018 American Sexually Transmitted Diseases Association