The vaccine that protects people against most cervical cancers elicits an immune response so potent that just a single dose will do, according to the World Health Organization.
An April review by the WHO's Strategic Advisory Group of Experts on Immunization concluded that one dose of human papilloma virus (HPV) vaccine "delivers solid protection against HPV" comparable to the two-dose schedule most adolescents in Australia currently receive.
The WHO recommended nations update their vaccination schedules accordingly.
And in some parts of the world, the wheels are already in motion.
In February, the UK's vaccine advisory committee issued advice to change the HPV vaccine schedule to a single dose for under-14s.
Evidence that one dose of the HPV vaccine is enough has been building for some time, according to Julia Brotherton, medical director of population health at the Australian Centre for the Prevention of Cervical Cancer.
"We have a limited supply of the vaccine, and it's very expensive," said Professor Brotherton, who is also a public health physician at University of Melbourne.
But how do we know one dose provides enough protection, and should Australia — one of the first countries to roll out the HPV vaccine nationwide — make the switch from two shots to one?
Remind me: what does the HPV vaccine do?
There are two approved HPV vaccines in Australia. Currently, the most used is Gardisil-9, available on the National Immunisation Program.
It protects against seven cancer-causing HPV types — not just cervical cancer, but also anus and throat cancers — and two types that cause genital warts.
In 2018, it replaced an earlier version of Gardisil that was quadrivalent, meaning it immunised against four types of HPV.
The other HPV vaccine, Cervarix, is bivalent. It protects against HPV types 16 and 18 only.
Because HPV spreads through sexual contact, vaccines are best given to people before they're sexually active.
In Australia, they're mostly administered to adolescents under 15, usually around 12 or 13 years old.
When the HPV vaccine was first introduced for non-immunocompromised adolescents under the National HPV Vaccination Program in 2007, a "completed course" was considered three doses over six months.
That changed in 2018, after studies showed two doses of the same vaccine, spaced at least six months apart, worked just as well.
(People starting HPV vaccination at 15 years or older, or who are immunocompromised, are still recommended to get three doses, if possible.)
And now, it seems one dose does the trick.
How do we know one dose is enough?
In 15 or so years since the HPV vaccine was first rolled out, researchers have tracked cervical cancer rates in millions of girls and women around the world.
But recent studies have presented compelling evidence that just one dose of the vaccine is sufficient.
The first hint came from a vaccine trial in Costa Rica. It was designed to evaluate the efficacy of three doses, but a group of women in the trial inadvertently received only one or two doses.
"This wasn't intentional," Professor Brotherton said.
"People got pregnant or something else happened, which meant they only got one dose.
The vaccine in the Costa Rica study was bivalent. Would the same hold for a quadrivalent vaccine?
An answer would come from India, where a large trial into a three-dose schedule was stopped partway through. This meant many of the girls in the trial, aged between 10 and 18 years old, received just one dose.
"But what we saw coming out of that cohort study was that the quadrivalent vaccine did, again, show equivalent levels of protection in the girls that only got one dose as those who got two or three," Professor Brotherton said.
While these and other studies, including data from Australia and the US, were intriguing, Professor Brotherton said the "pivotal study" was likely the randomised controlled trial that ran in Kenya.
Some girls received multiple doses of HPV vaccine — either bivalent or nine-valent, like Gardisil-9 — while others got one dose. A third cohort acted as the control and received a meningococcal vaccine.
In a paper published in April this year, the team found efficacy for a single dose of either bivalent or nine-valent HPV vaccine was 97.5 per cent.
"It's this staggering finding that I think has really been convincing to the WHO," Professor Brotherton said.
Why is one dose enough?
The HPV vaccine, which was developed at the University of Queensland by Ian Frazer and Jian Zhou in the 1990s, is made of what are known as "virus-like particles".
These are proteins that, when injected into our body, reassemble into a sphere that looks like the HPV shell, which our immune system makes antibodies against.
It's this spherical conformation that's thought to be important in developing long-lasting immunity to the virus, Professor Brotherton said.
"We think what's going on is [the sphere is] making the body respond a lot like it would to a real virus.
"And compared to a natural infection, the antibody levels you get [with vaccination] are sky high."
That's because HPV has evolved ways to slip past our immune defences.
Will Australia switch from two doses to one?
Quite possibly. National immunisation schedules are reviewed, and changes are recommended, by the Australian Technical Advisory Group on Immunisation (ATAGI).
A Department of Health spokesperson said "ATAGI routinely reviews any vaccine where there is significant development in the evidence with potential material impact on the vaccination schedule".
Australia already has decent HPV vaccination coverage, Kirby Institute epidemiologist and senior research fellow Dorothy Machalek said.
About 79 per cent of children aged 15 (80 per cent of girls and 77 per cent of boys) have had two HPV shots.
Add those who've only had one vaccine, and that total proportion jumps to 85 per cent.
"Those are pretty high rates, which have slowly increased over time since the start of the program [in 2007 for girls and 2013 for boys]," Dr Machalek said.
But there are good reasons for Australia to follow the WHO's lead and switch to a single-dose schedule for children — not least because it halves the cost of vaccination, she added.
How much the Australian government spends on Gardisil-9 each year isn't public, but it's not cheap.
Since introducing the HPV vaccine onto the National Immunisation Program in 2012, it has spent "close to $386 million on HPV vaccines and distributed around 6.4 million doses", which works out to an average of about $60 per dose.
This price can vary, with the manufacturers charging between $US4.50 to $US154 ($6.50 to $223) per dose.
For comparison, the hepatitis B vaccine costs less than $US1 a dose.
More HPV vaccines are coming down the line, such as China's bivalent Cecolin vaccine, which will help meet demand and drive prices down.
Australia adopting the single-shot schedule would also send a signal to low- and middle-income countries that have low HPV vaccine uptake, perhaps due to hefty costs and tricky logistics, Dr Machalek said.
These are areas where the HPV vaccine is most needed: of the roughly 340,000 deaths from cervical cancer in 2020, 90 per cent of those were in low- and middle-income countries.
That said, some of the highest HPV vaccine rates are in countries like Rwanda, where 98 per cent of eligible girls received their first dose between 2011 and 2018, and Bhutan, which has more than 90 per cent coverage of adolescent girls.
Australia is developing a cervical cancer elimination strategy in response to the WHO's global initiative to quash the disease, Professor Brotherton said.
Part of the WHO's strategy is aiming for 90 per cent of 15-year-old girls fully vaccinated by 2030.
"And obviously, if you only need one dose instead of two, it makes it much more feasible, and much more affordable."
