The Unrealized Promise of HPV Vaccination

The human papillomavirus (HPV) is an underappreciated threat to women’s health. A sexually transmitted virus that infects girls when they are young, HPV can lie dormant for years and threatens to develop into cervical cancer decades later, killing women in the prime of their lives. Accelerating the introduction of several highly effective HPV vaccines during early adolescence therefore presents a transformational opportunity to save lives and livelihoods. But strengthening HPV vaccination is not only a long-term strategic investment that could help win the global fight against cervical cancer—getting delivery right for HPV vaccines presents an unrealized near-term opportunity to strengthen immunization across the life course and contribute to the defense against future pandemic threats.

HPV vaccination platforms can serve as an entry point for adolescents to access many other health services, including routine and emergency interventions such as Covid-19 vaccination. Yet as high costs and volatile supply have created implementation challenges, countries have tended to undervalue HPV vaccination programs, devoting resources to other seemingly more immediate health threats. As a result, HPV vaccination coverage has lagged far behind that of other vaccines. This gap has expanded further as the Covid-19 pandemic has stretched health systems to their limits and HPV vaccine programs have been paused—global coverage has plummeted 15 percent since 2019. Beyond the operational challenges, the need for early intervention to prevent viral infection before girls reach sexual maturity means that HPV vaccination can sometimes stir controversy and provoke sensitivities around sexual norms, puberty, or fertility in some communities.

Meanwhile, cervical cancer continues to kill one person every two minutes, with the majority of those deaths disproportionately concentrated among women in Sub-Saharan Africa.

To regain lost ground and fully realize this opportunity to safeguard women’s health and strengthen a foundation for pandemic preparedness, the United States and global partners should consider the following strategies to bolster HPV immunization:

1. Plan long-term to stabilize supply. The global supply of HPV vaccines is improving, but has been unpredictable and is likely to remain tenuous as manufacturers scale up production. As international organizations such as Gavi, the Vaccine Alliance continue to negotiate prices down, bilateral and multilateral partners could provide targeted assistance to help both low- and middle-income countries forecast their vaccine needs over the next several years to ensure demand meets increasing supply and eventually stabilizes the marketplace.

2. Integrate services to build resilience. There is an opportunity to link existing local health programs provided to young adolescents with HPV vaccine delivery. This could make HPV vaccination more cost-effective for countries, less burdensome for health workers, more accessible for families, and less vulnerable to disruption in the face of future health crises.

3. Focus on demand generation. Introducing an unfamiliar vaccine to an underreached, potentially hesitant adolescent population at the sensitive age of puberty requires targeted efforts to build trust, acceptance, and uptake in communities. This is expensive and time-intensive. Committing additional financial resources to countries that are introducing HPV vaccination, over a longer timeline—including through Gavi, the Vaccine Alliance—could help provide low-income countries the resources they need to generate and sustain demand for HPV vaccines.

The push for expanded HPV vaccination is motivated by an imperative to eliminate one of the world’s deadliest cancers. But the failure to prioritize and scale such a powerful tool would also be a wider missed opportunity: a chance to build bridges for girls and young women to access critical health services, including and beyond HPV vaccination, during future health security emergencies.

Persistent Challenges

The 2006 World Health Organization (WHO) prequalification of the first HPV vaccines was a major moment for women’s health. Approximately 4.5 percent of all global cancer cases are attributable to HPV, and the vast majority—604,000 cases and 342,000 deaths in 2020 —are from cervical cancer, the fourth-most common and deadly cancer in women. The original HPV vaccines from Merck and GSK were shown to be over 90 percent effective in preventing most HPV-related cancers, and could reduce cervical cancer mortality by up to 99 percent if paired with screening and treatment later in life. But even with an armory of such powerful and cost-effective vaccines, integrating them into national immunization schedules has proven difficult due to a combination of cost, supply, delivery, and demand challenges, and under-prioritization by political leadership in the face of other immediate health threats.

High Costs Drive Disparity

At the time they were introduced, HPV vaccines were more expensive than other vaccines and limited in supply, meaning that high-income countries were able to purchase doses and introduce the vaccines much earlier and more quickly than low- and middle-income countries. The 147 countries and territories that have introduced HPV vaccination since 2006 are still disproportionately high-income, and cover just a third of eligible girls—aged 9 to 14 years-old—globally. Meanwhile, low- and middle-income countries bear over 80 percent of cervical cancer cases and 90 percent of deaths, with the greatest concentration of incidence and mortality in Sub-Saharan Africa, where it is the leading cause of cancer death in women.

To address this disparity, in 2012 Gavi, the Vaccine Alliance negotiated the HPV vaccine cost down from $100 per dose for the highest income countries to just $4.50 per dose for the low-income countries it supports. Gavi also began to support country introduction efforts, cofinancing the vaccines themselves along with initial delivery costs. Both Merck and GSK have committed to provide HPV vaccines to countries at the same Gavi-negotiated price for a limited time after they “graduate” from Gavi support to become fully self-financing.

Still, more work is needed to close the equity gap.

Middle-income countries, which have historically been ineligible for Gavi support, face particular challenges. Some progress has been made, with Gavi’s new middle-income-countries strategy allowing for targeted support to countries above the traditional income eligibility levels, and manufacturers offering lower, scaled pricing for middle-income clients. Even so, countries in the Americas that procure HPV vaccines through the PAHO Revolving Fund, which negotiates collectively on behalf of the region’s mostly middle-income countries, still pay twice the cost per dose of Gavi-eligible countries. Middle-income countries in other regions that self-finance their vaccines through UNICEF pay at least triple. These high prices limit countries’ appetite to pursue introduction. Even some Gavi-eligible countries such as Ghana, which has implemented successful HPV pilot projects, have not yet scaled immunization nationally out of uncertainty over how they would sustain programs once they eventually became ineligible for Gavi pricing.

In 2016, as the speed of introductions continued to lag, Gavi and the WHO Strategic Advisory Group of Experts on Immunization (SAGE) took steps to incentivize uptake of HPV vaccines on a national scale: expanding the number of countries eligible for Gavi introduction support, reducing the dosing schedule from three to two doses, and allowing countries more flexibility in designing their programs. These policy and financing adjustments led to a surge in demand, peaking with a record 16 national introductions in 2019. At the same time, the United States recommended HPV vaccine use for adults up to 45 years old leading companies to prioritize sales to this expanded market, and leaving behind low- and middle-income countries where the burden of disease is greater. The continuing supply shortages have delayed country introductions and left many adolescent girls unprotected and missing a critical link to access the health system.

Harnessing Innovation to Improve Supply

There are only a handful of licensed manufacturers capable of producing the authorized HPV vaccines, and they were unable to scale up to accommodate the unexpected surges in demand after 2016. This has contributed to enduring limitations on global supply that continue to restrict the scale and reach of HPV vaccination programs.

Although shortages are expected to continue until at least 2024, there are signs that supply constraints are beginning to ease. The new bivalent vaccine Cecolin®—manufactured by Chinese company Innovax—received WHO prequalification in October 2021, and is available to countries with Gavi support. Two additional products from Walvax (China) and Serum Institute of India have been licensed in their respective countries, and another candidate from the China National Biotec Group (Sinopharm) has entered phase 3 trials. Additional manufacturers in developing countries are expected to enter the market.

A new policy recommendation may help alleviate cost and supply challenges further: in April 2022, the WHO SAGE advised that countries could switch from a two-dose vaccination regimen to an off-label single-dose schedule, given that one dose of HPV vaccine showed high protection against the most carcinogenic strains of HPV. There are major financial and operational benefits to this shift, which would functionally double the supply of vaccine courses by cutting the dosage in half. Single dosing would also eliminate the need to follow up with clients for subsequent doses or conduct costly “catch-up” campaigns, which have been persistent challenges for reaching populations with multi-dose vaccines, including Covid-19 vaccines.

But uncertainties remain about single dosing, and the switch must be made with caution. It will be important to strengthen screening programs to ensure that single-dose immunity endures in the long-term as women age and their risk of developing cervical cancer increases. Especially if more low-resource countries adopt single dosing, this monitoring and evaluation will be critical to avoid an inequitable two-tiered approach to protection. And the single-dosing decision does not apply to some of the highest burden populations in Sub-Saharan Africa, including the population of immunodeficient HIV-positive women, which needs multiple doses to achieve protection and are the most vulnerable to HPV infection, with six times the likelihood of developing cervical cancer.

Efforts to build widespread demand for and strong delivery of HPV vaccines have been limited in recent years as supply struggled to keep pace. Now, as these new innovations allow manufacturers to expand and stabilize global supply, global demand must also rise to meet it to sustain the marketplace.

Designing a Delivery Platform

Compared to interventions for younger children and infants, there are fewer established opportunities to reach adolescents with health services. And neither childhood immunization nor reproductive and maternal health programs are positioned to assume responsibility for programs for adolescent girls. This has left HPV vaccination programs at a disadvantage because they are limited in their ambitions by constraints on supply and funding; this also leaves adolescents more vulnerable to falling through the cracks of the wider healthcare system.

Given these limitations, countries have had to weigh various tradeoffs as they design their HPV vaccination programs and concentrate on the age and approach through which they expect to achieve the highest initial coverage based on local circumstances. Countries with high adolescent school enrollment, such as India or Zimbabwe, may opt for school-based HPV vaccination campaigns, even if those programs may be costly, time-intensive, and leave limited resources to reach out-of-school girls. Some countries with strong routine health services, such as Senegal or Tanzania, may elect for a mix of outreach at schools and fixed health facilities. Others may rely on fixed health facilities over community outreach, because of the lower operational costs.

The Covid-19 pandemic demonstrated the fragility of all these approaches, as pandemic restrictions closed schools and facilities, limited community outreach programs, and raised the costs for all immunization activities. Since HPV vaccination tends to be managed separately from routine childhood immunization, it was among the one of the first programs to be put on hold as healthcare workers were diverted to the Covid-19 response. Global HPV vaccination coverage, which already lagged behind coverage against other vaccine-preventable diseases, continues to backslide, having fallen to just 12 percent in 2021—and even lower in Gavi-supported countries. Since the beginning of the pandemic, 3.5 million more eligible girls have missed out on HPV vaccination, and even more girls lost access due to increasing strain on healthcare resources and delays or postponement of new introductions. And the longer pandemic disruptions continue, as more girls miss their vaccinations or drop out of school completely, the more intensive the effort will be required to reach those girls once programs resume.

Since the impact of HPV vaccination has long-delayed returns, countries have prioritized more immediately deadly outbreaks of diseases such as measles, focusing on restarting those campaigns. Other countries are keen to introduce the new but expensive and supply limited malaria vaccine. Finding creative ways to integrate HPV vaccination with those campaigns or other targeted adolescent and family services may help increase the value of HPV vaccination to health officials and political leaders amid constraints on health budgets and health worker bandwidth, and enable programs to endure in the face of future shocks. These services may include HIV prevention and treatment, malaria prevention, and sexual and reproductive health services, depending on the country context. At the same time, bundling HPV vaccination within a broader suite of services can help soften the stigma and community sensitivity that may arise when discussing a health intervention against a sexually transmitted virus. Countries can integrate services across existing sites where families are likely to seek healthcare services, such as pediatric offices, and collocate many different programs to make adolescent services more accessible and economical for families.

Sustaining Demand

As the Covid-19 response has shown, the availability of vaccines is not always accompanied by a demand for vaccination. To be fully effective, efforts to expand the reach of vaccinators must be complemented by equally strong efforts to ensure that once adolescents can access vaccines, they and their parents are aware of them and inclined to accept them.

This will require significant investment year after year, beyond the limited timeline for Gavi introduction grants: finding time and resources to train and empower healthcare workers, especially female healthcare workers; identifying all the eligible girls in the age cohort; and performing social mobilization to encourage adolescents to seek out the vaccines.

Much more education and community outreach is needed to make the link between immunization, cancer prevention, and women’s health more explicit for health workers, schoolteachers, and families, and to convince parents that the time and cost of seeking vaccination services for their adolescent daughters will be worth their while. It will be critical to consider what messages and messengers—perhaps including cancer survivors or their family and friends—will be the most effective in championing the value of early prevention through vaccination, and achieving lasting behavior change. The most effective methods, such as peer mentorship and social mobilization platforms, will and indeed already have yielded dividends far beyond HPV vaccination by building adolescent awareness of safety measures during the Covid-19 pandemic, and they could be used similarly in the case of future emergencies and for future adolescent vaccines.

This personalized, proactive outreach is also a more effective counterpoint to misinformation and stigma, which has been especially pernicious in regard to HPV and Covid-19 vaccines. Countries have taken different approaches to mitigate rumors and achieve higher levels of coverage. In Zimbabwe, the more unfamiliar Covid-19 and HPV vaccines were delivered at the same time as more established, trusted childhood vaccines such as inactivated polio vaccines. This demonstrates the extra value that HPV vaccination could have, were it to become more widely accepted, in paving the way for new vaccines against unknown threats.

A Smart Investment

With global attention focused on raising the coverage of routine immunizations that have languished during the Covid-19 pandemic, now is a critical moment to regain momentum. There is high-level commitment to expanding HPV vaccination among multinational and bilateral partners: in November 2020 the WHO released its Global strategy to accelerate the elimination of cervical cancer as a public health problem for 2030, which ambitiously calls for 90 percent of girls to be fully vaccinated against HPV by the time they are 15 years old. The United States has been an active player through the efforts of the U.S. Centers for Disease Control and Prevention, the National Academies, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), and the U.S. Agency for International Development, through its support of Gavi. But in the face of recent regression, there is a need for a revitalized approach to recover HPV vaccination coverage and put programs back on a forward-leaning trajectory.

Many proven, localized, creative strategies to improve the performance of HPV vaccination programs are simply waiting to be scaled. The United States and its bilateral and multilateral allies will need to work with low- and middle-income country partners to stabilize the marketplace, better integrate services, and mobilize communities, one clinic and school at a time. These efforts will provide enormous returns by expanding service delivery for adolescent girls and eliminating preventable cervical cancer deaths for decades to come. But the wider, strategic investment may prove equally valuable in the near term by building a bulwark against the next inevitable pandemic threat.

Michaela Simoneau is a research associate with the Global Health Policy Center at the Center for Strategic and International Studies in Washington, D.C.

The author would like to thank Katherine E. Bliss for her invaluable guidance throughout the project and Noelle Huhn for her tremendous support with the original background research. Sincere thanks to the many other colleagues who generously shared their time and expertise in the development of this commentary , including Mackenzie Burke, CSIS; Zoey Diaz, global vaccine delivery expert; Amber D’Souza, Johns Hopkins University; Janet Fleischman, CSIS; Scott LaMontagne, PATH; Christopher Morgan, Jhpiego; J. Stephen Morrison, CSIS; Elizabeth Noonan, USAID (former); Lora Shimp, John Snow, Inc; Anissa Sidibe, Gavi; and Susan Wang, CDC, among others. These individuals contributed to the commentary in their individual capacity, not as representatives of their respective organizations, and language included in this commentary does not imply institutional endorsement by the organizations that experts represent. This is not a consensus document and the opinions expressed are the sole responsibility of the author.

Commentary is produced by the Center for Strategic and International Studies (CSIS), a private, tax-exempt institution focusing on international public policy issues. Its research is nonpartisan and nonproprietary. CSIS does not take specific policy positions. Accordingly, all views, positions, and conclusions expressed in this publication should be understood to be solely those of the author(s).

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