Effectiveness of school-based and high-risk human papillomavirus vaccination programs against cervical dysplasia in Manitoba, Canada Christiaan H. Righolt 1 , Songul Bozat-Emre 1,2 and Salaheddin M. Mahmud 1 1 Vaccine and Drug Evaluation Centre, Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada 2 Epidemiology and Surveillance, Manitoba Health, Seniors and Active Living, Government of Manitoba, Winnipeg, MB, Canada The effectiveness of a vaccination program is influenced by its design and implementation details and by the target population characteristics. Using routinely collected population-based individual-level data, we assessed the effectiveness (against cervical dysplasia) of Manitoba’s quadrivalent human papillomavirus (qHPV) routine school-based vaccination program and a short-lived campaign that targeted women at high-risk of developing cervical cancer. Females ≥9 years old who received the qHPV vaccine in Manitoba (Canada) between September 1, 2006, and March 31, 2013 (N = 31,442) were matched on age and area of residence to up to three unvaccinated females. Cox proportional hazards models were used to estimate qHPV VE against high-grade (HSILs) and low-grade squamous intraepithelial lesions (LSILs) and atypical squamous cells of undetermined significance (ASCUS). Among 14–17-year-old participants who had Pap cytology after enrollment, the adjusted qHPV VE estimates were 30%(17–58%) and 36% (21–48%) against the detection of HSILs and LSILs, respectively. There was, however, no evidence of program effectiveness among females vaccinated at ≥18 years of age and among those with a history of abnormal cytology, who were mostly vaccinated as part of the high-risk program. Estimates of VE for females vaccinated in the school-based program are consistent with the expected benefits from qHPV vaccination. No similar benefits were detected among women vaccinated at an older age, and those with abnormal cytology, who were targeted by the high-risk program. Further efforts should be targeted at achieving higher vaccine coverage among preadolescents, prior to the initiation of sexual activity. Introduction Human papillomavirus (HPV) is the most common sexually transmitted infection (STI), 1 and the cause of virtually all cervical cancers. 2 The quadrivalent HPV (qHPV) vaccine (Gardasil, Merck) is approved for use in over 100 countries, including Canada (which was one of the first few countries to introduce it), 3 for preventing infection with HPV types 16 and 18 that are responsible for 70% of cervical cancers worldwide 4 as well as HPV types 6 and 11, which are responsi- ble for most genital warts. 5 The qHPV vaccine became available for sale in Manitoba in 2006, and was introduced as a publicly funded three-dose school-based program for all girls in grade 6 (11–12 years old) beginning in September 2008. 6 In 2015, the program switched to a two-dose schedule, starting with the 2004 birth cohort. 7,8 The program’s goal remained to vaccinate preado- lescent girls under the typical age of sexual activity, as the current vaccines do not treat existing HPV infection or its consequences. 3 In 2013, vaccine uptake in this age group was slightly lower (65%) in Manitoba than the national average Key words: HPV vaccine, cervical dysplasia, vaccine effectiveness, cervical abnormalities, human papillomavirus Abbreviations: ASCUS: atypical squamous cells of undetermined significance; CCSR: Cervical Cancer Screening Registry; CIN: cervical squa- mous intraepithelial neoplasia; CIS: in situ cervical cancer; HPV: human papillomavirus; HR: hazard ratio; HSIL: high-grade squamous intrae- pithelial lesion; ICD: International Classification of Diseases; LSIL: low-grade squamous intraepithelial lesion; MH: Manitoba Health; MIMS: Manitoba Immunization Monitoring System; MPR: Manitoba Population Registry; Pap: Papanicolaou test; PHIN: Personal Health Identifica- tion Number; qHPV vaccine: quadrivalent human papillomavirus vaccine; RCT: randomized clinical trial; STI: sexually transmitted infection; VE: vaccine effectiveness Conflicts of Interest: SMM has received unrestricted research grants from Merck, GlaxoSmithKline, Sanofi Pasteur, Pfizer and Roche- Assurex. None of the other authors have any conflicts of interest that could affect the design or analysis of this project. Grant sponsor: Merck Canada Inc DOI: 10.1002/ijc.32135 History: Received 17 Sep 2018; Accepted 8 Jan 2019; Online 17 Jan 2019 Correspondence to: Dr. Salaheddin Mahmud, MD PhD FRCPC, Vaccine and Drug Evaluation Centre, Department of Community Health Sciences, University of Manitoba, 333–750 McDermot Avenue, Winnipeg, MB, Canada R3E 0T5, E-mail: salah.mahmud@gmail.com International Journal of Cancer IJC Int. J. Cancer: 145, 671–677 (2019) © 2019 UICC Cancer Epidemiology