Cervical cancer is the fourth most common cancer among women globally, with more than 95 percent of cases resulting from HPV infection. HPV vaccines are highly effective; since their introduction, they have significantly reduced the incidence of HPV infections and precancerous cervical lesions. But though they have been available since 2006, HPV vaccines remain out of reach for girls and women in many low- and middle-income countries (LMICs)—where 90 percent of cervical cancer deaths occur.
The World Health Organization’s (WHO’s) global strategy to accelerate elimination of cervical cancer calls on countries to, by the year 2030, fully vaccinate 90 percent of girls with HPV vaccine by age 15. As more countries consider introducing HPV vaccine and as new, affordable HPV vaccine options enter the market, country governments must determine the best use of limited budgets to maximize resources and improve population health. PATH is supporting country decision-making through efforts to inform and demonstrate the health and economic benefits of HPV vaccination—including through a series of country-led cost-effectiveness analyses that help answer the question: are HPV vaccination programs cost effective?
Over the past several years, we’ve worked with partners in Mongolia, the Philippines, Mozambique, Kenya, and Burkina Faso to understand the cost-effectiveness of HPV vaccine in their specific countries.
The anatomy of cost effectiveness
A cost-effectiveness analysis examines the costs and health impact of one or more interventions by comparing them to each other and to the status quo to determine whether the intervention is a good use of resources. These analyses incorporate different pieces of information—including disease burden, vaccine effectiveness and impact, delivery costs, and illness costs—to help determine whether an intervention is a good value for money.
“The results of these analyses can help local leaders estimate the long-term health and economic impacts of different vaccination program,” said Anne Schuind, MD, HPV Vaccines Initiative Lead at PATH. “They are essential tools when trying to make decisions about the most appropriate vaccine programs, products, and schedules to implement all while ensuring sustainability.”
Our project, for example, compared the four HPV vaccines that are currently WHO prequalified—Merck’s GARDASIL® and GARDASIL®9; GSK’s Cervarix™; and Xiamen Innovax Biotech’s Cecolin®—to each other, and to no vaccination. This information can help the countries that have already introduced HPV vaccine (the Philippines, Kenya, Mozambique, and Burkina Faso) determine whether they are using the most cost-effective product or schedule; and help the countries that haven’t yet introduced but are considering it (Mongolia) determine whether HPV vaccine is cost effective at all, and if so, which products and schedules are the best choice.
There is no single magic number for cost-effectiveness, though; what works for one country might not for another. Moreover, because cost effectiveness is comparative, a vaccine can only be considered cost effective in relation to something else. Health economists determine this by estimating the incremental cost-effective ratio (ICER), which is the difference in intervention costs divided by the difference in health outcomes (such as years of life lost due to early death and/or disability) and weigh it against a given country’s willingness-to-pay threshold, which is defined as how much that country is willing to pay to avert one year of life lost. If the ICER falls below the willingness-to-pay threshold, the intervention is considered cost-effective; if it exceeds it, it is not.
Context matters
In all studies conducted as part of this project, HPV vaccination was cost effective when compared to no vaccination. These results align with those of other HPV vaccine cost-effectiveness analyses, suggesting that HPV vaccination programs may be cost effective globally.
That’s encouraging—but nuance matters and deciding whether to introduce HPV vaccine or change an existing vaccination program is more complicated.
“HPV vaccination saves lives and improves health—and health economic assessments like cost-effectiveness analyses can help ensure it makes good financial sense, too.”— Clint Pecenka, PhD, Director of Health Economics at PATH
While HPV vaccine is cost effective, affordability can still be a challenge, especially for middle-income countries that are no longer eligible for subsidized pricing via Gavi, the Vaccine Alliance. For instance, Kenya may soon transition away from Gavi support and see its vaccination program costs increase—exceeding US$10 million per year for HPV, the study demonstrated. Moreover, countries face competing health needs and may sometimes need to prioritize one intervention over another—meaning, even a cost-effective vaccination program may get skipped due to affordability limitations.
It's important to reassess cost-effectiveness as the HPV vaccine landscape and country circumstances change. Gavi transitions can impact affordability and vaccine pricing can change. New vaccines can enter the global market; for instance, Cecolin, a lower priced HPV vaccine, received WHO prequalification in 2021—11 years after the first HPV vaccines were prequalified. And vaccination recommendations can evolve; in 2022 the WHO’s Strategic Advisory Group of Experts on Immunization endorsed a single-dose HPV vaccination schedule as an alternative to the two-dose schedule, which impacts how much vaccine a country needs to procure to protect girls and women. HPV vaccination programs in Kenya and the Philippines, for instance, predate Cecolin’s approval and the single-dose endorsement—and our research shows that a product or schedule switch could be more cost effective or even cost saving in these countries.
Product choice in particular influences the degree of cost effectiveness. Pricing is of course a concern—GARDASIL 9, for instance, which at the time of study cost more than other vaccine options and isn’t supported by Gavi, generally wasn’t cost effective for the countries studied. But in addition to price variations, the virus types the vaccine protects against matter. The currently available vaccines directly protect against the two major virus types that cause cancer, and some potentially offer cross-protection against additional virus types not included in the vaccine. Type of protection offered impacts health outcomes, which in turn impacts cost effectiveness.
For instance, our research showed that in Mongolia, Cervarix may offer better value for money than GARDASIL even though Cervarix was priced higher at the time of study. This is because Cervarix has shown cross protection against some virus types not included in the vaccine but that were prevalent in a notable percentage of cervical cancer cases in Mongolia. Similarly, the study in Kenya showed that Cecolin provides better value for money when cross-protection is not considered, whereas Cervarix is the most cost-effective choice when it is considered.
“Vaccines are one of the best buys in public health but that doesn’t mean countries should say ‘yes’ to every new vaccine or schedule change that comes along,” said Clint Pecenka, PhD, Director of Health Economics at PATH. “HPV vaccination saves lives and improves health—and health economic assessments like cost-effectiveness analyses can help ensure it makes good financial sense, too. In the case of HPV vaccination, research shows that vaccination is often a wise economic choice for countries.”
Economics as a guide for decision-making
Though results are specific to the country studied, they could help guide countries in similar geographic regions or with similar disease burdens or economic conditions.
“Studies like these are essential—the economics of HPV vaccination can provide countries with crucial data to support health systems decisions and changes,” said Cathy Ndiaye, PhD, Director of HPV Vaccines Programs at PATH. “Whether they’re considering HPV vaccine for the first time or have been providing it for years, countries need to examine the economic benefits of different products and schedules, especially as new vaccines become available and policy recommendations evolve and change.”
The work doesn’t end here. PATH is continuing to support LMICs in understanding whether and how HPV vaccine is cost effective in their countries and are initiating new studies that can help advance sustainable HPV vaccine access and uptake around the world.
