CIDRAP Op-Ed: One HPV vaccine dose may be enough, but how we get to that answer matters
Jake Scott, MDToday at 11:55 a.m.
Human Papillomavirus (HPV)
Childhood Vaccines
The American Academy of Pediatrics (AAP), which represents the nation's pediatricians, is considering whether one dose of human papillomavirus (HPV) vaccine is enough for adolescents. James Campbell, MD, who chairs its infectious diseases committee, told the Associated Press that a conclusion could come later this year.
In January, the Department of Health and Human Services (HHS) under its secretary, Robert F. Kennedy Jr., cut the recommended HPV schedule to one dose. If the AAP also recommends one dose, it will be easy to read that as an endorsement of Kennedy's decision. That would not make the two decisions equivalent.
The number may be the same, but the decisions would rest on very different processes. And that difference matters.
What the evidence shows
The strongest evidence comes from a large trial in Costa Rica, published in the New England Journal of Medicine in December 2025. About 20,000 girls aged 12 to 16 received either one or two doses and were followed for five years.The trial asked whether one dose was meaningfully less protective than two. It was not. Compared with a separate group of unvaccinated girls and young women, one dose and two doses were each at least 97% effective against infections with HPV types 16 and 18 that lasted six months or more. Those two types cause most cervical cancers. Protection showed no sign of fading over the five years.
A trial in Kenya has since shown a single dose protecting young women for at least four and a half years.
In May, CIDRAP's Vaccine Integrity Project, which reviews the scientific evidence on vaccines, published a review of the HPV vaccine research. (I contributed to the project's earlier respiratory vaccine review but had no role in this one.) In studies that followed people for more than five years, vaccinated women had a 66% lower risk of cervical cancer itself, not just precancerous changes, and an 80% lower risk if they were vaccinated at 16 or younger.
The review, together with two Cochrane reviews published in November 2025, also addressed the safety concerns that have followed this vaccine for years. They found no link between HPV vaccination and serious side effects. They also found no link with Guillain-Barré syndrome, a rare condition in which the immune system attacks the nerves and causes weakness, or with chronic fatigue syndrome, infertility, problems in pregnancy, or premature ovarian failure, in which the ovaries stop working before age 40.
Two recent studies reported an association with postural orthostatic tachycardia syndrome (POTS), a condition in which the heart rate rises abnormally when a person stands up, or with related conditions. Both had important limitations. One relied on unverified reports and compared groups of very different ages, and the other found an association with a broader category of conditions only in 18- to 26-year-olds. The Cochrane reviews, which include randomized trials, found no increased risk of POTS.
Kennedy has told a different story for years. He worked as a lawyer and consultant on lawsuits against Merck over its HPV vaccine, Gardasil, and has falsely claimed that it raises the risk of cervical cancer. The evidence shows the opposite.
By the end of 2025, 93 countries were using a one-dose schedule.
What we don't know yet
Nearly all the single-dose evidence comes from girls and young women, and it measures protection against infection and precancer of the cervix. No study has compared one dose with two in boys, or measured protection against HPV cancers elsewhere in the body.That gap is important. Based on 2018 to 2022 data, the Centers for Disease Control and Prevention (CDC) estimates that HPV causes about 16,800 cancers in American men each year, about 13,600 of them at the back of the throat, including the tonsils and base of the tongue. There is no established screening test for these cancers.
The trial that showed the vaccine prevents disease in males used three doses. Two doses later became the standard for children who start before age 15 after studies showed that two doses produced immune responses comparable to three. No study has shown that one dose does the same in boys, and the federal working group that reviewed this question noted some evidence that boys produce lower antibody levels than girls after a single dose. Merck, which makes Gardasil, announced in 2024 that it plans trials comparing one dose with three in males and in females aged 16 to 26.
The United Kingdom moved both boys and girls to one dose in 2023. Canada recommended one dose for everyone aged 9 to 20 in 2024, while noting that the evidence for one dose was limited to studies in females. Both applied the evidence from girls to boys. That is a reasonable judgment. Whatever the AAP decides, it should be equally clear about what has been shown and what is being inferred.
The federal working group did not discuss changing the three-dose recommendation for people with weakened immune systems.
Why the process matters
The AAP has published its own vaccine recommendations since the first edition of its Red Book in 1938, decades before the federal Advisory Committee on Immunization Practices (ACIP) was created to advise the CDC. The two have disagreed before. In 1989, both recommended a second measles vaccine dose but disagreed on the age to give it. Their first joint schedule, in 1995, allowed either age.That kind of process was under way for HPV. A working group of the ACIP, including representatives of the AAP and other medical societies, had been meeting monthly since July 2024 and planned to bring its recommendations to the full committee for votes in June 2025. That month, Kennedy removed all of the committee's voting members.
In January, HHS changed the schedule to one dose. Its assessment cited some of the same studies, but there was no committee vote, and the working group's review was never finished. A federal court put the change on hold in March, and an appeals court is scheduled to hear arguments next week, on October 6.
If the AAP moves to one dose, it will be after the kind of evidence review that the federal process never finished.
Where things stand
For now, CDC's recommendation has not changed. Children who get their first dose between ages 9 and 14 receive two doses. Those who start at 15 or older, and those with weakened immune systems, including people with HIV, receive three. That applies to boys and girls.If the AAP recommends one dose, families may hear different numbers from different sources for a while. That is understandable, and it is not a reason to wait.
The larger problem is the number of adolescents who never start the series. According to CDC data published in September, more than one in five adolescents aged 13 to 17 had never received a dose of HPV vaccine in 2025, and only 63.4% were up to date. HPV vaccination rates did not increase for the fourth year in a row.
By comparison, about 89% received the tetanus-diphtheria-pertussis (whooping cough) booster and the meningococcal vaccine, which are recommended at the same age. One fewer dose makes the series easier to finish. It does nothing for a child who never starts.
The message is the same whatever the AAP decides. HPV vaccine prevents cancer. It is recommended at age 11 or 12 and can be started as early as 9. A child who has not had a first dose does not need to wait for the dosing debate to be settled.
Dr. Scott is a clinical associate professor of infectious diseases at Stanford University School of Medicine, and a coauthor of "Updated evidence for COVID-19, RSV, and Influenza Vaccines for 2025-2026" in the New England Journal of Medicine.
The opinions voiced in CIDRAP Op-Ed pieces are the authors' own and do not necessarily represent the official position of CIDRAP.