Comparative analysis adds evidence in favor of one-dose HPV vaccination in girls

An analysis of data from two clinical trials in sub-Saharan Africa, a region with one of the highest cervical cancer rates worldwide, suggests that just one dose of a human papillomavirus vaccine is enough to protect girls from HPV infection for up to two years. 

These data support previous evidence showing the efficacy of a single dose and the recent World Health Organization endorsement of a single-dose HPV vaccine schedule. 

The analysis compared antibody levels in blood serum samples taken from young women aged 15–20 and girls aged 9–14. The study appears in The Lancet Global Health.  

Frederick National Laboratory’s Vaccine, Immunity, and Cancer Directorate performed the standardized laboratory assays to quantify the antibody levels in blood serum and participated in the large, multinational collaboration involving the trials. 

Several types of HPV, a pathogen most often transmitted through sexual contact, are key drivers of cervical cancer and other genital cancers, as well as some oropharyngeal and anal cancers. Effective vaccines for preventing infections and associated cancers came on the market in 2006 and were originally approved as three-dose regimens. 

That has posed challenges to vaccination in resource-limited areas, such as sub-Saharan Africa, where the burden from HPV-related cancers is high. Demonstrating that one dose is as effective as three could make vaccination more practical in these regions—and make existing vaccine stockpiles stretch further. 

Data in favor of a one-dose vaccine have been mounting for the past decade, and this latest study represents another encouraging piece of evidence. 

Evaluating results from two trials 

The study spanned samples from the KEN SHE Study in young Kenyan women and the DoRIS trial in Tanzanian girls. Participants in KEN SHE received one dose of either the Cervarix vaccine, formulated to counter two high-risk strains of HPV, or the Gardasil-9 vaccine, formulated against the same two strains and seven others. Participants in DoRIS received one, two, or three doses of either Cervarix or Gardasil-9. For the analysis, the researchers focused on samples from the women and girls who received one dose. 

They found that the young women in KEN SHE and the girls in DoRIS who received the same vaccine had comparable antibody levels at 24 months after a single dose.  

These latest results mean scientists can confidently infer that the girls in DoRIS—owing to having comparable antibody levels to the women in KEN SHE—are also protected, said Ligia Pinto, Ph.D., Vaccine, Immunity, and Cancer Directorate director and a senior investigator on the study. 

“[We’re] using an immune marker to bridge to a virological marker or endpoint—in this case, persistence of infection—which is another inference to a precancer disease endpoint,” she said. “That’s why serology is becoming so important to streamline vaccine assessment, particularly in cases in which you cannot do HPV testing.” 

Connecting dots and filling in gaps 

Immunobridging studies like the comparison between KEN SHE and DoRIS offer a way to evaluate reduced-dose vaccine regimens in young girls, the primary target group for HPV vaccination but in whom evaluating efficacy is difficult because of the age group or time needed to accrue virological or disease endpoints. 

“In the sense of the bridging aspect itself, multiple factors are involved that we had to consider when designing the testing scheme for these samples,” said Troy Kemp, Ph.D., an author on the study and the scientific manager of the HPV and COVID-19 Serology Laboratories within the Vaccine, Immunity, and Cancer Directorate. “To minimize bias from the two trial groups, the assays had to be well controlled and standardized.” 

In addition to overcoming practical concerns involving testing, such studies can provide a wealth of information about how the immune system responds at different ages. Individuals’ immune systems change as they age, so it isn’t possible to assert, without data, that people at certain ages are protected from an infection just because an older or younger population is protected. Trials like these fill the gap. 

‘Meaningful step forward’ 

While the findings are another mark in favor of one-dose vaccination, the study only examined antibody levels up to two years, the timepoint at which they plateau after HPV vaccination. It’s possible that those levels will decline over time or that a greater divergence between age groups may appear. 

In addition, the analysis only encompassed several hundred participants, all of whom had intact immune systems. Further studies in immunocompromised girls and young women will be important to evaluate one-dose responses in individuals with compromised immune systems. 

Still, the study represents a meaningful step forward in an expanding field—and importantly, the data were collected amid real-world conditions in areas with endemic malaria and high HPV infection and cervical cancer rates, Pinto said. These add strength to the findings. 

The Vaccine, Immunity, and Cancer Directorate worked closely with the London School of Hygiene & Tropical Medicine, which led the study, and other collaborators. The group at Frederick National Laboratory is supporting or involved in seven one-dose HPV vaccine studies around the world.