HPV vaccine: Some studies say one and done might be better

This week, at the World Health Organization’s 76th World Health Assembly, health leaders from nearly 100 countries will join with thousands of others who have signed off on a global initiative to eliminate cervical cancer.

Globally, cervical cancer is the fourth most common type of cancer in women, according to WHO, but many cases are completely preventable with the human papillomavirus vaccine.

HPV is a group of more than 200 related viruses. Many don’t cause any symptoms at all. Some strains cause warts, and some cause cancer. The HPV vaccine protects against the strains that cause most HPV-related cancers.

“Vaccines are bringing the dream of eliminating cervical cancer within reach,” WHO Director-General Tedros Adhanom Ghebreyesus said in his remarks to the World Health Assembly on Monday.

The vaccine is recommended for children because it works best before someone has been exposed to the virus. HPV is often spread through sexual contact, and the US Centers for Disease Control and Prevention says that almost every sexually active person who is not vaccinated will get HPV at some point.

The vaccine’s introduction to the US in 2006, along with more regular screening, has led to a notable drop in cervical cancer cases and deaths in the US, according to the American Society of Clinical Oncology. Cervical cancer rates among the first American generation to get vaccinated have dropped significantly. Among women ages 20 to 24, cervical cancer incidence rates declined 65% from 2012 through 2019, according to the American Cancer Society.

But not every country has the same vaccination options, which is part of the reason WHO has been pushing to change the way doctors give the HPV vaccine.

The organization has ambitious goals. By 2030, WHO hopes to get 90% girls around the world fully vaccinated against HPV by the time they turn 15. At the moment, coverage is just 13%, according to WHO.

Currently, in the majority of countries including the US, the vaccine is given in a series of two or three shots. The CDC suggests vaccination around age 11 or 12, but the process can be started as early as 9.

In 2022, WHO’s Strategic Advisory Group of Experts on Immunization decided instead that based on the latest science, one shot would provide enough protection, and countries should offer a one- or two-dose schedule for girls and women ages 9 to 20 and a two-dose shot with a six-month interval for women older than 21.

This single-dose approach could be a game-changer for the prevention of cancer, WHO said. Logistically, one dose is a lot easier to administer and would be much cheaper than multiple doses. Studies also show that when people need a series of shots over time, they’re less likely to get them all.

The UK, Ireland, Australia and at least 18 other countries have switched their protocols to align with WHO’s recommendations.

A recent study provided additional evidence that one shot of the vaccine is highly effective over three years, if not longer. A single dose has an efficacy of 97.5% a year and a half later and is comparable to multidose regimens 24 or 30 months out, the researchers found.

The study, which has not been fully published, focused on a randomized double-blind controlled trial – the gold standard of research – to see whether one shot would protect healthy young women who were vaccinated at three study sites in Kenya. It involved 2,275 participants: A third got a vaccine that protects against two HPV types, a third got a nonavalent vaccine that protects against nine types, and a third got a control, a meningococcal vaccination.

Scientists collected cervical swabs every six months that were tested for HPV DNA. They also looked at the effectiveness of the vaccine in each young woman after three years.

“We reported that at three years, efficacy continued to be very high, and the effect of the vaccine was durable, with no waning effect,” said Dr. Ruanne Barnabas, co-principal investigator on the study and chief of infectious diseases at Massachusetts General Hospital. “These results add to the growing body of evidence to support use of a single dose, especially to facilitate access and coverage for HPV vaccines, which are among the most effective vaccines that we have. They work so well, and we know that they prevent cancer. And so this is another tool we can use to reduce cervical cancer.”

Another slice of this study, published last year in the journal NEJM, had similar results.

An official from the Gates Foundation, which funded the research, said that if the HPV vaccine were a single dose, twice as many people could get protection in an ideal situation.

“This data is really cementing confidence around the durability of that protection,” said Peter Dull, who leads the foundation’s work supporting HPV vaccine development

Dr. Kathleen Schmeler, a professor in the Department of Gynecologic Oncology and Reproductive Medicine at MD Anderson, agreed that the study found “really good evidence” that one shot would work.

Schmeler, who was not involved with the new research, said observational studies from 2014 and 2020 also showed that immunity with one dose is lasting.

“Some could argue that the WHO decision to recommend just one was premature and that we need to wait for years and years of data, but sometimes the enemy of good is perfect, as they say,” she said.

It may be helpful for researchers to check in after a decade to see whether protection is falling off and whether people need to be revaccinated.

“The US has the luxury of having a lot of resources, but not everywhere is so lucky. If you could just have to do one dose, it just simplifies things so much and brings the cost down so much,” Schmeler said.

Dr. Ted Teknos, an otolaryngology-head and neck specialist at University Hospitals in Cleveland, is more cautious.

He said the findings of the study are “encouraging,” but he wants to see longer-term results.

“These patients will need to be studied longer to ensure that one shot is sufficient for a lifetime for protection,” said Teknos, who is also a clinical professor in the Department of Otolaryngology at Case Western Reserve University’s School of Medicine and who was not involved in the research.

Dr. Quintin Pan, who is working on HPV research at University Hospitals Seidman Cancer Center, is also reluctant to change the current protocol. His concern is that one shot may not protect against all the strains of HPV.

“So [it’s] really similar to the Covid vaccine, where one vaccine appears to be only effective for certain variants, and then you can have other variants that are not going to be eliminated with only certain vaccines. This is certainly the case with HPV as well,” said Pan, a professor in the Case Western Department of Otolaryngology who wasn’t involved with this study.

A one-and-done approach to the HPV vaccine could be a huge help around the world, experts say. Dull said a large number of countries haven’t even introduced the vaccine, in part because of the cost and the implementation challenges of multiple doses.

“In many of these geographies, giving two doses a year apart is really complicated. So this just reduces the barrier to countries that really want to introduce the vaccine but have logistical challenges or cost challenges, that it helps to remove one critical barrier to bring additional countries into into use of this important vaccine,” he said.

Teknos said he hopes more people – girls, boys and men – get the shot. The CDC recommends it for everyone, but WHO considers boys and older females “secondary targets” who should get vaccinated only “where feasible and affordable.”

Globally, the number of boys who have gotten it has lagged. A 2019 study found that about 4% of boys had received the full course of the vaccine, compared with 15% of girls.

HPV doesn’t just cause cervical cancer. It can also lead to cancer in the back of the throat or in the anus, penis, cervix, vagina or vulva.

Despite the success with reducing rates of cervical cancers, Teknos said, the US has seen a huge surge in HPV-related head and neck cancers. Cancers of the throat have gone up 300% since 1988, he said. There’s also been an increase in other HPV-related anal and penile cancers.

“HPV-related head and neck cancers has become an epidemic in the United States,” Teknos said.

Dr. Anisha Abraham, chief of the Division of Adolescent and Young Adult Medicine at Children’s National in Washington, said she too would like to see more long-term data before switching to a different vaccine schedule. But she’d also like more people to get the HPV vaccine.

“Starting the vaccination series early can really protect kids from cancers and diseases that are caused by HPV and potentially could save their lives. So I think that’s really, really important,” Abraham said.