Introduction of prophylactic human papillomavirus (HPV) vaccines has the potential to dramatically decrease morbidity and mortality from anogenital and oropharyngeal cancers. However, data from vaccine clinical trials cannot predict vaccine effectiveness in ?real-world? community settings, and introduction of a 9-valent (in addition to a 2- and 4-valent) vaccine in 2015 and reduced dosing schedules (from 3 to 2 doses) in 2016 could further modify vaccine effectiveness. The impact of vaccine introduction can be efficiently and accurately evaluated by HPV surveillance studies that assess vaccine effectiveness, herd protection, cross-protection (decrease in HPV types genetically related to vaccine types), and type replacement (increase in non-vaccine- type HPV due to a reduction in vaccine types). We previously conducted 4 HPV surveillance studies in women (2006-2017) and 2 in men (2013-2017). Among women, we found evidence for vaccine effectiveness (but lower effectiveness with 1 vs. 3 doses), herd protection, and cross-protection; no evidence for type- replacement; and an unexpected increase in non-vaccine-type HPV in unvaccinated women. Among men, we found preliminary evidence for vaccine effectiveness and herd protection. Continued investigation through the proposed renewal is essential to achieve the following objectives: 1) assess the effects of 9-valent vaccine introduction and reduced dosing schedules on effectiveness, 2) elucidate long-term trends in herd protection, 3) identify signals of diminished cross-protection or emerging type-replacement, and 4) determine mechanisms for increases in non-vaccine-type HPV in unvaccinated women.
The specific aims are to: 1) determine long- term trends in 4-valent - and emerging trends in 9-valent - HPV prevalence among vaccinated women (2006- 2023) and men (2013-2023) to assess HPV vaccine effectiveness, and among unvaccinated women and men to assess herd protection; 2) assess the differential impact of the number of vaccine doses received on vaccine-type HPV, by age; 3) determine trends in non-vaccine-type HPV prevalence among vaccinated women and men, to examine for persistent cross-protection and emerging type replacement; and 3) explore biological and behavioral mechanisms for the increase in non-vaccine-type HPV in unvaccinated women. Our approach will be to enroll 1,600 women and men in two additional surveillance studies, to characterize the impact of vaccine introduction across a total of 6 time periods in women (2006-2023, N=2,400) and 4 in men (2013- 2023, N=1,600). The proposed research is innovative because the resulting data could shift current research and clinical practice paradigms in the areas of vaccination and virology, and the research plan utilizes novel concepts, approaches and new methodologies to explore mechanisms driving HPV trends. The proposed research is significant because the data will provide key evidence for: 1) vaccination and cervical cancer screening programs; 2) public health communications and risk-reduction counseling; and 3) cost-effectiveness analysis and policy decisions: these will help to reduce disparities and mortality due to HPV-related cancers.

Public Health Relevance

In this study, we will characterize the epidemiologic impact of human papillomavirus (HPV) vaccine introduction from 2006 to 2023, among diverse populations of young women and men in a community. The study will provide a comprehensive assessment of the post-marketing impact of HPV vaccine introduction, including 9- valent HPV vaccine introduction and reduced dosing schedules, and will provide key evidence for HPV vaccine recommendations, cervical cancer screening programs, public health messaging, cost-effectiveness analysis, and policy decisions that aim to reduce rates of cervical cancer and other HPV-associated cancers. These outcomes directly address several Healthy People 2020 (https://www.healthypeople.gov/) objectives, including reducing HPV infection in women, reducing the death rate from cervical cancer, and increasing male and female HPV vaccine coverage.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI104709-06A1
Application #
9739446
Study Section
Infectious Diseases, Reproductive Health, Asthma and Pulmonary Conditions Study Section (IRAP)
Program Officer
Turpin, Delmyra B
Project Start
2013-01-18
Project End
2023-07-31
Budget Start
2019-08-16
Budget End
2020-07-31
Support Year
6
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Smith, C; Ding, L; Gorbach, P M et al. (2018) Who's Not Protected in the Herd? Factors Associated with Vaccine-Type HPV in Unvaccinated Women. J Pediatr Adolesc Gynecol 31:89-93
Chandler, Emmanuel; Ding, Lili; Gorbach, Pamina et al. (2018) Epidemiology of Any and Vaccine-Type Anogenital Human Papillomavirus Among 13-26-Year-Old Young Men After HPV Vaccine Introduction. J Adolesc Health 63:43-49
Morrow, Charlene; Thomas, Rachel; Ding, Lili et al. (2018) Prevalence of potential sexual abuse in adolescents and young adults and feasibility of an assessment and management plan used in three research projects. Res Nurs Health 41:166-172
Thomas, Rachel; Higgins, Lisa; Ding, Lili et al. (2018) Factors Associated With HPV Vaccine Initiation, Vaccine Completion, and Accuracy of Self-Reported Vaccination Status Among 13- to 26-Year-Old Men. Am J Mens Health 12:819-827
Ding, Lili; Widdice, Lea E; Kahn, Jessica A (2017) Differences between vaccinated and unvaccinated women explain increase in non-vaccine-type human papillomavirus in unvaccinated women after vaccine introduction. Vaccine 35:7217-7221
Mesher, David; Soldan, Kate; Lehtinen, Matti et al. (2016) Population-Level Effects of Human Papillomavirus Vaccination Programs on Infections with Nonvaccine Genotypes. Emerg Infect Dis 22:1732-40
Whittemore, Dana; Ding, Lili; Widdice, Lea E et al. (2016) Distribution of Vaccine-Type Human Papillomavirus Does Not Differ by Race or Ethnicity Among Unvaccinated Young Women. J Womens Health (Larchmt) 25:1153-1158
Kahn, Jessica A; Widdice, Lea E; Ding, Lili et al. (2016) Substantial Decline in Vaccine-Type Human Papillomavirus (HPV) Among Vaccinated Young Women During the First 8 Years After HPV Vaccine Introduction in a Community. Clin Infect Dis 63:1281-1287
Drolet, Mélanie; Bénard, Élodie; Boily, Marie-Claude et al. (2015) Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis. Lancet Infect Dis 15:565-80