Exactly two years ago, the World Health Organization launched a new global strategy to eliminate cervical cancer. That strategy included a target of having 90% of girls fully vaccinated with an HPV vaccine by the age of 15. But to date, only 123 countries have introduced the vaccine in their national immunization programs, according to Dr. Kate O’Brien, the director of WHO’s Department of Immunization, Vaccines and Biologicals. As of 2021, only 13% of the world’s girls have been fully vaccinated.
Vaccines protecting against cervical cancer have been around since 2006. But access remains limited due to supply constraints. WHO however expects the HPV vaccine market to change soon with the entry of new manufacturers from China and India.
WHO has to date prequalified three HPV vaccines: those manufactured by GSK and Merck, who have been the main manufacturers, and one developed by Chinese company Xiamen Innovax Biotech.
But there’s now another vaccine by Walvax Biotechnology in China, which was approved in China in March and now has an application for WHO prequalification, and another vaccine developed by the Serum Institute of India whose manufacturing is expected to start by the end of 2022.
O’Brien expects their entry to contribute to a scale up of human papillomavirus vaccine supply globally, potentially improving access in the coming years.
“You're very much at this point of a real change in the market. And we're going to see, two years from now, this story about who's using [the] HPV vaccine is going to be a really different story,” she told Devex in an interview.
O’Brien said HPV vaccines are “a very heavily demanded vaccine.” But there are several potential barriers to scaling up access to them.
Devex spoke with O’Brien on the factors that have to date contributed to low HPV vaccine coverage globally, the potential impact of the entry of new manufacturers on pricing, and current threats surrounding access.
The text below has been edited for length and clarity.
According to the World Health Organization, only 13% of the population received two doses of HPV vaccines globally. Why do we have such low coverage?
Let me start by saying whatever is happening today is a reflection of the past. So there has been in the past a supply constraint, and … it has resulted in the necessity, in particular through the Gavi program, to pace the introductions, in order to assure that any introduction that happens is an introduction that can be followed up with sufficient numbers of doses that the program continues. We never want a country to initiate a program, and then be in a position where they can't continue it.
So partly, it has been in the past a supply constraint. And as a result of the supply constraint, then a management of the pace of introductions, and the demand. That's been the major issue around why we are where we are. But in addition to that, because of the pandemic, we've also seen a backsliding in HPV coverage.
[This is] in part because it's deployed largely, not entirely, but largely through school-based programs to girls. And school programs were one of the areas that took a very big hit as a result of the pandemic.
The Strategic Advisory Group of Experts recommended one-dose HPV vaccinations back in April. Can you talk about that?
At the April SAGE meeting, for the second time we reviewed data on what we referred to as a reduced-dose schedule approach. And the assessment was there was sufficient data in order to be confident that a single-dose regimen had equivalent performance to the two-dose regimen. However, the data for that regimen are not available for all of the products. So manufacturers do need to provide data around what happens after the first dose in order for that to be an authorized schedule from a regulatory perspective. And so we do point to the products for which those data are available.
In addition to that, for countries that are immunizing boys, there aren't data on the single-dose schedule in boys. But there's no reason that SAGE could think of why it wouldn't work as a one-dose regimen.
But our recommendation is really sort of specific to the products for which there is data, and the fact that this evidence is in females. And we are also specific that this is not a regimen for those who are HIV infected. Given the impact of HIV, a two-dose regimen is still needed.
Most of the time when people talk about HPV vaccines, it’s almost always for women and girls. What’s the current access situation for men and boys?
There are 123 countries that have a national HPV program. Forty-seven countries also vaccinate their boys. So that gives you a feel. Now, of the 123 countries that have female programs … those 123 countries represent only 33% of the world's girls … which you can take to mean that there are some very big countries that have not yet introduced [the vaccine in national immunization programs] — China, for instance, [and] India.
With more manufacturers in the market, what could potentially be a barrier to scaling up access to HPV vaccines?
Of course, on the supply side, nothing is guaranteed until you really see the supply. So we have full confidence and expectations that there won't be barriers to additional pre-qualification, that the manufacturers will stay in the marketplace, that they will be able to deploy … these vaccines and actually produce them at scale. I don't see that to be a particular risk. We see high interest from countries wanting to introduce it. I don't see that as a barrier.
However, I think we have to be realistic. Countries are facing an enormous number of priorities right now. So I think the biggest threats to HPV is that countries have so many demands on them right now, and so many resource issues. We have economic issues going on, we've got conflict situations scaling across the world, we've got inflation, we've got macroeconomic issues that are going to make it difficult for countries to balance their books in their budget, and to be able to commit to introducing new vaccines.
[Also,] Gavi is the funding source for these vaccines for countries. And Gavi, as you know, goes through funding cycles. So Gavi will be entering another replenishment in the coming years — the current investments go through 2025. If there was a reduction in the funding to Gavi, that would be a threat to this program.
In WHO’s recent report, the average price per dose of HPV vaccines varies: from $4.51 via UNICEF procurement to $20.06 for self-procuring middle-income countries to $81.61 for self-procuring high-income countries. Will the introduction of new manufacturers from China and India drive down the cost of HPV vaccine?
We do have very significant tiered pricing in the HPV market. … And we do expect that with more suppliers coming in that there will be what we refer to as market shaping. And this is what we see with basically all products — as the market matures, as developing country vaccine manufacturers come in, as the volumes that manufacturers can scale to their economies of scale, that these prices do drop. And we do expect that there will be further reduction in price for HPV vaccines and probably very significant reductions in price.