Moving toward the elimination of cervical cancer: modelling the health and economic benefits of increasing uptake of human papillomavirus vaccines

Short Communication


Moving toward the elimination of cervical cancer: modelling the health and economic benefits of increasing uptake of human papillomavirus vaccines


A. Smith, MPH*, N. Baines, MPH*, S. Memon, MPH*, N. Fitzgerald, MA(Econ)*, J. Chadder, MSc*, C. Politis, MPH*, E. Nicholson, MHSc*, C. Earle, MD MSc*, H. Bryant, MD PhD*


doi: http://dx.doi.org/10.3747/co.26.4795


ABSTRACT

Background

The human papillomavirus (hpv) is a common sexually transmitted infection and a primary cause of cervical cancer. The Government of Canada has set a target of reaching 90% hpv vaccine coverage among adolescents by 2025. Here, we examine hpv vaccine uptake in school-based immunization programs across Canada and explore how achieving the 90% target could affect the future incidence of cervical cancer, mortality, and health system expenditures in a cohort of Canadian women.

Methods

Data for hpv vaccine uptake in the most recent reported school year available in each jurisdiction were provided in 2017 by jurisdictional school-based immunization programs and were used to estimate a national weighted average of 67%. The OncoSim microsimulation model (version 2.5) was used to compare 3 different levels of hpv vaccine uptake (0%, 67%, 90%) on health and economic outcomes for a hypothetical cohort of all 5- to 10-year-old girls in Canada in 2015.

Results

Vaccine uptake for girls in school-based programs varied from 55.0% to 92.0% in the jurisdictions reviewed. The OncoSim model projects that increasing uptake to 90% from 67% would result in a 23% reduction in cervical cancer incidence rates (to 3.1 cases from 4.0 cases per 100,000, averaged across the lifetime of the cohort) and a 23% decline in the average annual mortality rate (to 1.0 deaths from 1.3 deaths per 100,000). Finally, the model projects that the health system will incur a cost of $9 million (1% increase) during the lifetime of the cohort if uptake is increased to 90% from 67%. Costs are discounted (1.5%) and expressed in 2016 Canadian dollars. Costs reflect the payer perspective.

Conclusions

Our model shows that increasing hpv vaccine uptake to 90% from current levels for girls in school-based immunization programs could result in substantial reductions in the future incidence and mortality rates for cervical cancer in Canada.

KEYWORDS: hpv vaccination, cervical cancer, OncoSim, cancer modelling, cancer outcome projections, cancer control

INTRODUCTION

The human papillomavirus (hpv) is one of the most common sexually transmitted infections in Canada and a primary cause of cervical cancer1. Approximately 70% of sexually active Canadians will acquire an hpv infection at some point in their lifetime1. Fortunately, most of those infections will resolve on their own. However, for the small proportion of women who become infected with a high-risk hpv strain, that infection can lead to the development of cervical cancer1.

Three hpv vaccines have been approved for use in Canada, all of which vary in the number of viral strains covered. However, each vaccine provides protection against at least 2 high-risk strains (hpv 16 and hpv 18), which are responsible for more than 70% of cervical cancer cases in Canada1.

Between 2007 and 2010, all provincial and territorial governments in Canada began to publicly fund hpv vaccination for eligible girls through school-based immunization programs2. In recent years, provinces and territories have moved to include boys in those programs2. The Government of Canada set a target of reaching 90% hpv vaccine coverage in Canadian adolescents by 20253.

The objective of the present paper was to compare hpv vaccine uptake in girls in provincial and territorial school-based immunization programs across Canada and to explore how achieving the 90% target uptake could affect future cervical cancer incidence, mortality, and health system expenditures for a modelled cohort of Canadian girls.

METHODS

Data for hpv vaccine uptake by school-aged girls were provided in 2017 by provincial and territorial school-based immunization programs for the most recently reported school year available in each jurisdiction. The data were used to estimate a national weighted-average uptake of 67% for school-aged girls across Canada.

The OncoSim microsimulation model (version 2.5) was used to calculate and compare the effect of 3 levels of hpv vaccine uptake (0%, 67%, 90%) on multiple health and economic outcomes of interest for a hypothetical cohort of all 5- to 10-year-old girls in Canada in 2015. Specifically, the model was used to project annual cervical cancer incidence and mortality rates (calculated as the number of cancer cases and deaths expected over the lifetime of the cohort of 100,000 women) assuming 0%, 67%, and 90% hpv vaccine uptake. Economic outcomes explored included projected costs for screening, treatment, and vaccination over the lifetime of the cohort, comparing a 67% hpv vaccine uptake with 0% and 90% uptake.

OncoSim is a microsimulation model that incorporates real-world clinical evidence and economic data to assess health and economic impacts of changes in cancer care policies and practice in Canada. The model draws on multiple data sources and expert opinion to determine standard disease-specific diagnostic and treatment practices, health care costs and utilities, and expected personal income and tax revenue4,5.

For the purposes of the calculations of interest here, the model assumes that all jurisdictions use a 2-dose schedule of quadrivalent vaccine and that vaccine efficacy is 100% with no waning over time, with herd immunity incorporated. The model also assumes that hpv 16 and hpv 18 cause more than 70% of cervical cancers. Cervical cancer screening was assumed to be triennial Papanicolaou (Pap) testing for women 21–69 years of age at the current Canadian average participation rate of 72%. For the Pap test, the model assumed a specificity of 97% and a sensitivity of 60% for detecting cervical intraepithelial neoplasia grade 2 or higher. Follow-up protocols for positive Pap test screens were based on current practice and are described elsewhere6. OncoSim and the associated hpv transmission model are described in greater detail elsewhere46.

RESULTS

HPV Vaccine Uptake in School-Based Immunization Programs in Canadian Provinces and Territories

School-based hpv vaccine uptake data were available for all provinces and territories except Nunavut. The target age group for vaccination and the number of doses considered to be a full course of vaccination varied by jurisdiction2. Uptake for girls who have completed a full course of hpv vaccination ranged from 55.0% in the Northwest Territories to 92.0% in Newfoundland and Labrador (Figure 1).

 


 

FIGURE 1 Percentage of girls who received a full course of the human papillomavirus (HPV) vaccine in the most recently reported school year, by province and territory. – = Data not available. aVaccination is offered in grade 6 in Saskatchewan; however, vaccine uptake is assessed yearly at age 13. Also, Saskatchewan moved to a 2-dose schedule starting in the 2015–2016 school year. bOntario now provides vaccination in grade 7; however, the vaccination administered in the 2015–2016 school year was to grade 8 students. cAlberta has since moved to a 2-dose schedule, starting in the 2018–2019 school year, and has changed their school grade for vaccination from grade 5 to grade 6. Data source: Provincial and territorial school-based immunization programs.

Projected Effect of Increasing HPV Vaccine Uptake to 90% (Target) from 67% (Current) on Average Annual Incidence and Mortality Rates for the Lifetime of the Cohort

Assuming that no girls in the cohort were vaccinated, the annual cervical cancer incidence rate (averaged across the lifetime of the cohort) is projected to be 7.4 cases per 100,000, and the annual mortality rate is projected to be 2.3 deaths per 100,000 (Figure 2). With 67% hpv vaccine uptake, the average annual incidence is projected to drop by 46% to 4.0 cases per 100,000 in the cohort, and the mortality rate is projected to decline by 43% to 1.3 deaths per 100,000 (Figure 2). If vaccine uptake were to be increased to 90%, the model projects that the average annual incidence rate would drop by an additional 23% (to 3.1 cases per 100,000) or by 58% compared with no vaccination. The mortality rate would decline by an additional 23% (to 1.0 deaths per 100,000) or by 57% compared with no vaccination (Figure 2).

 


 

FIGURE 2 Annual rates of cervical cancer incidence and mortality, averaged for the lifetime of the modelled cohort, with 0%, 67% (current), and 90% (target) human papillomavirus (HPV) vaccine uptake. Cervical cancer incidence and mortality rates are not age-standardized. The user-defined cohort is hypothetical and consists of all 5- to 10-year-old girls in Canada in 2015.

Projected Effect of Increasing HPV Vaccine Uptake to 90% (Target) from 67% (Current) on Lifetime Screening, Treatment, and Vaccination Costs

The OncoSim model projects that fewer colposcopies, cervical biopsies, and clinical treatments for warts, precancerous lesions, and invasive cervical cancer are required as hpv vaccine uptake increases in the cohort. When comparing 67% uptake with no vaccination, reductions in screening and treatment costs are expected to save $160 million over the lifetime of the cohort. If uptake were to be increased to 90% from 67%, the model projects that an additional $9 million (1% increase) in system costs would be incurred (Table I). Costs reflect the payer perspective and are expressed in 2016 Canadian dollars. Discounted costs (1.5%) are reported in Table I.

TABLE I Lifetime costs by percentage uptake of the human papillomavirus (HPV) vaccine in the modelled cohorta

 

DISCUSSION AND SUMMARY

Our results indicate that hpv vaccine uptake in school-based immunization programs varies widely across Canada. Only Newfoundland and Labrador is achieving the 90% target uptake (at the time the present data were collected). Nonetheless, results show that the current average uptake of 67% nationally is likely to translate into substantial reductions in future cervical cancer cases and deaths. Those findings align with previous modelling studies that, using a variety of vaccine targets and outcome measures, have demonstrated the long-term benefits for various health and economic outcomes of increasing hpv vaccine uptake712.

Nonetheless, our results present a strong case for continuing to work toward the 90% target, because the model projects that the greater coverage would result in a further 23% reduction in the annual cervical cancer incidence and mortality rates. Though not accounted for in the model, further benefits related to reductions in other hpv-associated cancers such as anal and oropharyngeal cancers could also be expected.

Although average hpv vaccine uptake in school-based programs was estimated to be 67% nationally at the time the present data were collected, vaccine coverage in the broader Canadian population (for which the vaccine is recommended) has not yet reached that level13, primarily because school-based hpv immunization programs became widespread in Canada only between 2007 and 2010, and because the programs traditionally targeted only girls 9–14 years of age2,13. Work therefore remains to be done to increase vaccine coverage in the broader population— something a number of jurisdictions have attempted to address through catch-up programs for older adolescents and young adults2.

In recent years, several jurisdictions in Canada began funding the 9-valent vaccine14. Although the present analysis is based on the quadrivalent vaccine, the transition to the 9-valent version is anticipated to have modest effects on the results reported here, given that the 2 hpv strains associated with the greatest proportion of cervical cancers (hpv 16 and hpv 18) are covered by both vaccines1517. One international study estimated that the 5 additional strains covered by the 9-valent vaccine are associated with approximately 18.5% of cervical cancer cases17. Nonetheless, shifting to the 9-valent vaccine is expected to further reduce overall hpv transmission and, if relatively similar in cost to the quadrivalent vaccine, could be more cost-effective16,17.

Another likely shift over the next few years in Canada is replacing the Pap test with primary hpv screening. Studies suggest that the latter practice might improve early detection rates and contribute to reductions in the cervical cancer incidence, although follow-up colposcopies and their associated costs are expected to increase18. Additional analysis using OncoSim is being conducted to explore how primary hpv screening could affect health and economic outcomes in the Canadian context.

The present analysis has some limitations. The costs calculated by the model do not account for any additional marketing or promotional expenditures that might be required to increase hpv vaccine uptake from current rates. Our analysis also does not account for some of the factors in the Canadian context that could affect overall hpv transmission and the cervical cancer incidence in future. Such factors include transitioning to the 9-valent vaccine, the inclusion of boys in school-based immunization programs, and partial protection that might be gained by those who receive a partial course of the vaccine2,16,19. Given those factors, our results likely underestimate the reductions in cervical cancer cases and deaths that could be expected upon achieving the 90% target uptake.

Increasing hpv vaccine uptake to 90% from current rates for girls in school-based immunization programs could mean a reduction in future cases of, and deaths from, cervical cancer in Canada. It is crucial that clinicians and other health care providers help promote the importance of the hpv vaccine so that Canada can realize the full health and economic benefits of publicly funded hpv vaccine programs.

ACKNOWLEDGMENTS

This analysis is based on the OncoSim model, which is led and supported by the Canadian Partnership Against Cancer (the Partnership), with model development by Statistics Canada through Health Canada funding.

The Partnership has endorsed the Union for International Cancer Control’s global pledge to eliminate cervical cancer. The Partnership will work with partners to understand opportunities to close remaining gaps in hpv vaccination and cervical cancer screening uptake in Canada.

CONFLICT OF INTEREST DISCLOSURES

We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

AUTHOR AFFILIATIONS

*Canadian Partnership Against Cancer, Toronto, ON.

REFERENCES

1 Public Health Agency of Canada. Human Papillomavirus (HPV) [Web page]. Ottawa, ON: Government of Canada; 2017. [Available at: https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/human-papillomavirus-hpv.html; cited 7 August 2018]

2 Canadian Partnership Against Cancer (cpac). Cervical Cancer Screening in Canada: Environmental Scan. Toronto, ON: cpac; 2017.

3 Government of Canada. Vaccination Coverage Goals and Vaccine Preventable Disease Reduction Targets by 2025 [Web resource]. Ottawa, ON: Government of Canada; 2018. [Available at: https://www.canada.ca/en/public-health/services/immunization-vaccine-priorities/national-immunization-strategy/vaccination-coverage-goals-vaccine-preventable-diseases-reduction-targets-2025.html; cited 25 February 2019]

4 Gauvreau CL, Fitzgerald NR, Memon S, et al. The OncoSim model: development and use for better decision-making in Canadian cancer control. Curr Oncol 2017;24:401–6.
cross-ref  pubmed  pmc  

5 Evans WK, Wolfson MC, Flanagan WM, et al. Canadian cancer risk management model: evaluation of cancer control. Int J Technol Assess Health Care 2013;29:131–9.
cross-ref  pubmed  

6 Miller AB, Gribble, S, Nadeau C, et al. Evaluation of the natural history of cancer of the cervix, implications for prevention. The Cancer Risk Management Model (crmm)—human papillomavirus and cervical components. J Cancer Policy 2015;4:1–6.
cross-ref  

7 Choi YH, Jit M, Gay N, Cox A, Garnett GP, Edmunds WJ. Transmission dynamic modelling of the impact of human papillomavirus vaccination in the United Kingdom. Vaccine 2010;28:4091–102.
cross-ref  

8 Bogaards JA, Xiridou M, Coupé VM, Meijer CJ, Wallinga J, Berkhof J. Model-based estimation of viral transmissibility and infection-induced resistance from the age-dependent prevalence of infection for 14 high-risk types of human papillomavirus. Am J Epidemiol 2010;171:817–25.
cross-ref  pubmed  

9 Malagón T, Drolet M, Boily MC, Laprise JF, Brisson M. Changing inequalities in cervical cancer: modeling the impact of vaccine uptake, vaccine herd effects, and cervical cancer screening in the post-vaccination era. Cancer Epidemiol Biomarkers Prev 2015;24:276–85.
cross-ref  

10 Peng HL, Tam S, Xu L, et al. Age-structured population modeling of hpv-related cervical cancer in Texas and US. Sci Rep 2018;8:14346.
cross-ref  

11 Baussano I, Dillner J, Lazzarato F, Ronco G, Franceschi S. Upscaling human papillomavirus vaccination in high-income countries: impact assessment based on transmission model. Infect Agents Cancer 2014;9:4.
cross-ref  pubmed  pmc  

12 Coupé VM, van Ginkel J, de Melker HE, Snijders PJ, Meijer CJ, Berkhof J. hpv 16/18 vaccination to prevent cervical cancer in the Netherlands: model-based cost-effectiveness. Int J Cancer 2009;124:970–8.
cross-ref  

13 Bird Y, Obidiya O, Mahmood R, Nwankwo C, Moraros J. Human papillomavirus vaccination uptake in Canada: a systematic review and meta-analysis. Int J Prev Med 2017;8:71.
cross-ref  pubmed  pmc  

14 Merck Sharp and Dohme Corporation. Provincially funded vaccination programs [Web resource]. Kenilworth, NJ: Merck Sharp and Dohme Corporation; 2018. [Available at: https://www.gardasil9.ca/provincial-programs/?province=alberta; cited 10 February 2019]

15 Khan MJ, Castle PE, Lorincz AT, et al. The elevated 10-year risk of cervical precancer and cancer in women with human papillomavirus (hpv) type 16 or 18 and the possible utility of type-specific hpv testing in clinical practice. J Natl Cancer Inst 2005;97:1072–9.
cross-ref  pubmed  

16 Yang DY, Bracken K. Update on the new 9-valent vaccine for human papillomavirus prevention. Can Fam Physician 2016;62:399–402.
pubmed  pmc  

17 Serrano B, Alemany L, Tous S, et al. Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect Agent Cancer 2012;7:38.
cross-ref  

18 Rebolj M, Rimmer J, Denton K, et al. Primary cervical screening with high risk human papillomavirus testing: observational study. BMJ 2019;364:1240.

19 Public Health Agency of Canada (phac). National Advisory Committee on Immunization (NACI) Statement: Update on the recommended Human Papillomavirus (HPV) vaccine immunization schedule [Web page]. Ottawa, ON: phac; 2016. [Available at: https://www.canada.ca/en/public-health/services/publications/healthy-living/update-recommended-human-papillomavirus-vaccine-immunization-schedule.html; cited 25 February 2019]


Correspondence to: April Smith, Canadian Partnership Against Cancer, 900–145 King Street West, Toronto, Ontario M5H 1J8. E-mail: april.smith@partnershipagainstcancer.ca

(Return to Top)


Current Oncology, VOLUME 26, NUMBER 2, April 2019








Copyright © 2019 Multimed Inc.
ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)