Many cancers are driven by complex interactions between genetic and environmental factors, making identifying singular causes challenging at best. When we think of ways to prevent such diseases, we may first consider lifestyle choices: eating healthier, not smoking, or not drinking excessively; and yet, we are likely still rolling the dice as to whether these will guarantee health in the long run. However, for cancers with known etiologies—such as those driven by viral infections—prevention can be as simple as getting a vaccine, as is the case for Hepatitis B and Human Papilloma virus (HPV). HPV can cause a variety of cancers in both men and women, but it’s most known for its ability to cause cervical cancer in women, which accounts for about 93% of HPV-related cancers (WHO). Cervical cancer was the fourth most common cause of cancer and cancer deaths in women in 2022 and appears to disproportionately affect middle- and low-income countries and those living with HIV. Vaccines against HPV have been available for nearly two decades and have shown to be incredibly effective in protection against HPV infection and development of HPV-related cancers; however, their administration in many heavily affected regions is difficult due to supply, cost, and logistic considerations. Making this issue even more complicated is the fact that current guidelines for HPV vaccine administration recommend 2- or 3-dose regimens, resulting in lower widespread accessibility and variable retention for the entire course of shots.
However, there is now evidence that an updated approach is in order for HPV vaccination, thanks to Dr. Denise Galloway, of the Fred Hutch Human Biology Division and Dr. Ruanne Barnabas (formerly UW), contributors to a recently published article in Nature Medicine. As a longer-term follow up to a mid-study evaluation published in 2022 in NEJM Evidence, this article showed that a single-dose of HPV vaccine can result in strong and durable protection from HPV infection. Despite this being a change from the previously licensed and recommended regimens, there was precedent to believe that one dose would provide comparable responses to two or three doses. This is because the virus-like particle used in the vaccine formulation can generate a strong immune response after just a single dose, not unlike what we observe with other standard one-dose vaccines. When asked why multiple doses was originally chosen for this vaccine, Dr. Galloway explained that the dosing was empirically based on the subunit Hepatitis B vaccination regimen at the time, which also followed a multi-dose series. However, it seemed like it was time to re-assess if that was truly the best approach.
To be able to conclusively address this, the research team designed and carried out a multicenter, randomized, placebo-controlled trial with young Kenyan women, aged 15-20, who would not otherwise be eligible for the WHO-recommended 2-dose vaccine series, which is administered to 9–14-year-old girls. Participants were randomized to one of three vaccine groups: bivalent (targeting two strains of HPV), nonavalent (targeting nine HPV strains), or control (meningococcal) vaccines. By the 18-month follow-up, the research group already saw a clear efficacy, resulting in significantly increased protection from HPV infection in groups receiving either HPV vaccine compared to those in the placebo group. “It was so striking after 18 months that we had to change the study design so that the girls in the placebo group got vaccinated then,” Dr. Galloway recalled. With their updated design, they implemented a blinded cross-over vaccination, wherein the placebo group then receives the vaccine, and the original vaccine groups receive a placebo. By 36 months, there was still evidence of a strong and durable protective response due to the vaccine, supporting their initial hypothesis that this would be an effective approach to vaccine administration. As follow-ups to this report, Dr. Galloway explained that they also planned a final 48-month assessment, as well as serological and B-cell response analyses, all of which will be helpful in building out a fuller picture of whether a single-dose HPV vaccine elicits long lasting and efficacious immunity.
As a result of this study, the WHO has already revised its recommendation for HPV vaccination to one dose, which represents a major milestone for the future of HPV vaccination and the prevention of cervical cancer. It is important to note that for young women living with HIV, “the current guideline remains for two-doses, as it has been observed that they don’t produce as good an antibody response,” explained Dr. Galloway. However, the team hopes to repeat the one-dose study in young women with HIV to potentially address this concern. Dr. Galloway highlighted that “one-dose will really be a game changer for low- and middle-income countries…since that is where nearly all of the deaths from cervical cancer occur”. In fact, cervical cancer rates are much lower in developed nations such as the U.S., in part due to effective screening and vaccine coverage; Dr. Galloway also expressed interest in whether these countries would chose to adopt the one-dose approach as well. Until then, however, she is grateful that the one-dose strategy could represent a scalable and cost-effective approach to increased vaccine accessibility in countries where HPV-related cancers are most concentrated, emphasizing that “Making a difference there will really save lives”.
The spotlighted research was funded by the Bill & Melinda Gates Foundation and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases (R.V.B.).
Fred Hutch/University of Washington/Seattle Children's Cancer Consortium members Drs. Denise Galloway, Elizabeth Brown, Rachel Winer, and Nelly Mugo contributed to this work.
Barnabas RV, Brown ER, Onono MA, Bukusi EA, Njoroge B, Winer RL, Galloway DA, Pinder LF, Donnell D, N Wakhungu I, Biwott C, Kimanthi S, Heller KB, Kanjilal DG, Pacella D, Morrison S, A Rechkina E, L Cherne S, Schaafsma TT, McClelland RS, Celum C, Baeten JM, Mugo NR; KEN SHE Study Team. Durability of single-dose HPV vaccination in young Kenyan women: randomized controlled trial 3-year results. Nat Med. 2023 Dec;29(12):3224-3232. doi: 10.1038/s41591-023-02658-0. Epub 2023 Dec 4. PMID: 38049621; PMCID: PMC10719107.