How a single HPV vaccine dose can prevent cervical cancer

In 2022, the World Health Organization (WHO) reviewed a compilation of data—including those collated and synthesized by the Single-Dose HPV Vaccine Evaluation Consortium—leading to a decision to endorse the alternative use of a single-dose HPV vaccination schedule.

While shifting from a multi-dose to a one-dose regimen promised logistical and financial advantages, WHO’s central question was whether the quality of the evidence supported this shift. Did the data suggest that one dose of HPV vaccine protects against cervical cancer just as well as a series of doses? Would that protection be long-lasting?

Immune response analysis paired with clinical observation can help answer these questions.

HPV vaccine is a subunit vaccine, which is a class of vaccines that uses a piece of the virus to generate an immune response. Researchers used an HPV protein called L1, an important region for the immune system’s interaction with the virus. When the vaccines teach the immune system to recognize L1, we’re able to fight the real virus in the future.

Subunit vaccines typically require subsequent inoculations (boosters) to generate an adequate immune response, which is why HPV vaccines were recommended on a three-dose schedule when they first became available in 2006. But the success of HPV vaccines surpassed even the most optimistic projections, and one observation was particularly surprising: young women who, for various reasons, had fewer doses of HPV vaccine—even just one dose—still had a strong immune response and were equally protected from HPV infection.

Protection from just one dose of a subunit vaccine was unprecedented. To understand what set HPV vaccines apart, researchers took a close look at the immune response.

In HPV vaccines, the L1 protein is delivered using a virus-like particle (VLP) mechanism, which retains the protein’s original shape. In its native shape, the protein behaves in a specific way: hundreds of these L1 VLPs (360, to be exact) link up to form a kind of super-sphere, with the L1 targets fanning outward around the perimeter, inviting swarms of B cells (a type of immune cell) to bind them through their cell surface antibodies.

This simultaneous response to multiple L1 proteins (as opposed to one or two L1 proteins) results in potent B cell activation signals, and these strong signals stimulate the development of long-lasting plasma cells (LLPCs). LLPCs continuously churn out large numbers of antibodies into the blood for round-the-clock extracellular surveillance duty, humming along as a consistent backdrop of our immune ecosystem.

Critically, LLPCs don’t depend on additional vaccine doses or virus exposures to continue production. True to their name, these cells provide long-lasting protection.

Evidence of this type of immune response has borne out in clinical observation: after an approximately one-year decline following a single dose of HPV vaccine, the antibody level stabilizes at a steady plateau and is sufficient to provide solid long-term protection from infection.

So far, we have data on antibody levels after one dose through up to 16 years post-vaccination. While monitoring will continue, given what we know about this type of immune response, the levels are unlikely to dramatically change in subsequent years, and are expected to maintain protection against the HPV infections that are at highest risk of becoming cervical cancer.

While single-dose schedules have been evaluated in widely used HPV vaccines, researchers will assess the performance of new products on a single-dose regimen.

In late 2024, WHO used data from a PATH-sponsored study to add Cecolin® to the list of vaccine product options for use on a single-dose schedule. And in early 2025, PATH initiated participant enrollment in a new study to assess a nine-valent product (designed to protect against nine types of HPV) on a single-dose schedule.

Continued data collection to support the availability of new products will help expand the number of vaccine options for country use and facilitate greater access.

Since WHO’s endorsement, nearly 70 countries have adopted a single-dose schedule. Additional doses that are repurposed to reach more women and girls will prevent more cases of cervical cancer and save more lives, especially in low- and middle-income countries, where screening and treatment are limited.

The discovery of the potential of single-dose HPV vaccination illustrates not only the fundamental importance of basic science but also of continuous clinical research following product development. Each step of the way, evidence dissemination is paramount.

As additional countries consider their options, the Consortium continues to present evidence to national policymakers and to provide independent, objective evaluation of new evidence on single-dose HPV vaccination as it becomes available.

For further reading:

- Evidence to inform decision-making on single-dose HPV vaccination policy

- Summary of JNCI Monograph: State of the Science of Single-Dose Prophylactic HPV Vaccination