The vaccine that protects people against most cervical cancers, according to the World Health Organization, elicits an immune response so potent that just a single dose is enough.
Most important points:
- The HPV vaccine immunizes against viruses that cause most cervical cancers, as well as some throat and anal cancers
- Research from around the world shows that a single dose of HPV vaccine elicits as much immune protection as two doses
- Countries are urged to adjust their HPV vaccination schedules accordingly
An April review by the WHO’s Strategic Advisory Group of Experts on Immunization concluded that a single dose of human papillomavirus (HPV) vaccine “provides solid protection against HPV” comparable to the two-dose schedule most adolescents in Australia currently receive.
The WHO has recommended that countries update their vaccination schedules accordingly.
And in some parts of the world, the wheels are already moving.
In February, the UK’s Vaccine Advisory Committee issued advice to change the HPV vaccine schedule to a single dose for children under 14.
Evidence that one dose of the HPV vaccine is enough has been building for some time, according to Julia Brotherton, Medical Director of Health at the Australian Center for the Prevention of Cervical Cancer.
“We have a limited supply of the vaccine and it is very expensive,” said Professor Brotherton, who is also a public health physician at the University of Melbourne.
But how do we know if one dose is enough protection, and should Australia – one of the first countries to roll out the HPV vaccine nationwide – make the switch from two injections to one?
Remember: What Does the HPV Vaccine Do?
There are two approved HPV vaccines in Australia. Currently, the most commonly used is Gardisil-9, available on the National Immunization Programme.
It protects against seven cancer-causing HPV types — not just cervical cancer, but 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 was immunized against four types of HPV.
The other HPV vaccine, Cervarix, is bivalent. It only protects against HPV types 16 and 18.
Because HPV spreads through sexual contact, vaccines are best given to people before they are sexually active.
In Australia, they are usually administered to adolescents under 15, usually around 12 or 13 years old.
When the HPV vaccine was first introduced to 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 that two doses of the same vaccine, spaced at least six months apart, worked just as well.
(People who begin HPV vaccination at age 15 or older, or who are immunocompromised, are still recommended to get three doses, if possible.)
And now it seems that one dose is enough.
How do we know that one dose is enough?
In about 15 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 provided compelling evidence that just one dose of the vaccine is enough.
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 study accidentally received only one or two doses.
“This was not meant to be,” Professor Brotherton said.
“People got pregnant or something else happened and they only got one dose.
The vaccine in the Costa Rica study was bivalent. Would the same be true for a quadrivalent vaccine?
An answer would come from India, where a large trial of a three-dose schedule was halted halfway through. This meant that many of the girls in the trial, aged between 10 and 18, received only one dose.
“But what we saw from that cohort study was that the quadrivalent vaccine again showed equivalent levels of protection in the girls who received only one dose as those who received two or three,” Professor Brotherton said.
While these and other studies, including data from Australia and the US, were intriguing, Professor Brotherton said the “critical study” was likely the randomized controlled trial conducted in Kenya.
Some girls received multiple doses of HPV vaccine — bivalent or nine-valent, such as Gardisil-9 — while others received one dose. A third cohort acted as a control and received a meningococcal vaccine.
In a paper published in April this year, the team found that the efficacy of a single dose of a bivalent or nine-valent HPV vaccine was 97.5 percent.
“It is this staggering finding that has really convinced the WHO,” said Professor Brotherton.
Why is one dose enough?
The HPV vaccine, developed in the 1990s by Ian Frazer and Jian Zhou at the University of Queensland, is made of so-called ‘virus-like particles’.
These are proteins that, when injected into our bodies, reassemble into a sphere similar to the HPV shell, which our immune system makes antibodies against.
It is this spherical conformation that is thought to be important in developing long-term immunity against the virus, Professor Brotherton said.
“We think what’s going on… [the sphere is] making the body react just like to a real virus.
“And compared to a natural infection, the antibody levels you get are [with vaccination] are towering.”
That’s because HPV has evolved ways to slip past our immune defenses.
Will Australia switch from two doses to one?
Very likely. National immunization schedules are reviewed and changes are recommended by the Australian Technical Advisory Group on Immunization (ATAGI).
A spokesperson for the Ministry of Health said: “ATAGI routinely reviews each vaccine when there is significant development in the evidence with a potential material impact on the vaccination schedule”.
Australia already has decent HPV vaccination coverage, said epidemiologist and senior research associate Dorothy Machalek of the Kirby Institute.
About 79 percent of 15-year-old children (80 percent of girls and 77 percent of boys) have had two HPV injections.
Add in those who have had only one vaccine, and that total share jumps to 85 percent.
“Those are pretty high rates, which have slowly increased over time since the program started.” [in 2007 for girls and 2013 for boys]said Dr Machalek.
But there are good reasons for Australia to follow WHO’s lead and switch to a single-dose schedule for children – not least because it cuts vaccination costs in half, she added.
How much the Australian government spends on Gardisil-9 each year isn’t public, but it’s not cheap.
Since the HPV vaccine’s introduction into the National Immunization Program in 2012, it has “spent nearly $386 million on HPV vaccines and distributed about 6.4 million doses,” which works out to an average of about $60 per dose.
This price can vary with the manufacturers charging between $4.50 and $154 ($6.50 to $223) per dose.
In comparison, the hepatitis B vaccine costs less than $1 per dose.
More HPV vaccines are coming to the market, such as the Chinese bivalent Cecolin vaccine, which will help meet demand and drive prices down.
Australia’s approval of the single-shot schedule would also send a signal to low- and middle-income countries that have low HPV vaccine uptake, perhaps due to high costs and tricky logistics, said Dr. Machalek.
These are areas where the HPV vaccine is most needed: Of the roughly 340,000 cervical cancer deaths in 2020, 90 percent fell in low- and middle-income countries.
That said, some of the highest HPV vaccine rates are in countries like Rwanda, where 98 percent of eligible girls received their first dose between 2011 and 2018, and Bhutan, where more than 90 percent of adolescent girls are covered.
Australia is developing a strategy to eliminate cervical cancer in response to the WHO’s global initiative to eradicate the disease, Professor Brotherton said.
Part of the WHO’s strategy is to have 90 percent of 15-year-old girls fully vaccinated by 2030.
“And of course, if you only need one dose instead of two, it makes it much more feasible and much more affordable.”