TORONTO - A new Canadian study offers some hope that two doses of HPV vaccines may work as well as the current regimen of three.
If that's true, it will help reduce the cost of the expensive public vaccination programs in Canada, but may also put HPV vaccination within reach in developing countries, where cervical cancer deaths are still common, said lead author Dr. Simon Dobson of the Vaccine Evaluation Centre of the University of British Columbia.
Dobson, who is a pediatric infectious diseases specialist, said the savings that could be made by cutting the third dose could be a real boon to public health — if the vaccine works well enough with two doses to protect against cancer-causing HPV infections.
"Can you stray off the licensed schedule because the public health value may outweigh the incremental benefit that you get from the extra dose?" he said in explaining the purpose of the study.
The work was published Tuesday in the Journal of the American Medical Association. It was funded by the ministries of health of British Columbia, Nova Scotia and Quebec.
Human papillomaviruses have been shown to be the cause of cervical cancer, as well as a range of head and neck cancers, penile cancer and anal cancer. Some strains of the viruses cause genital warts, which can require repeated visits to doctors and place a heavy burden on the health-care system.
In recent years, two new vaccines have come to market that protect against some strains of HPV. Gardasil, which is made by Merck Canada, protects against the two leading cancer-causing strains as well as two strains that cause genital warts. The second vaccine, Cervarix, is made by GlaxoSmithKline. It protects against the two leading strains that cause urogenital cancers.
But the vaccines are given in three doses and are expensive. They can cost between $400 and $500 per child if parents buy the vaccine. Large bulk purchases by provinces and territories secure lower prices, but the vaccines are still costly by public program standards.
All provinces and territories offer the vaccine for free to girls, with some starting in Grade 4 and most offering it in Grade 6. Ontario's program is the latest, offering the vaccine to girls in Grade 8.
Recently Prince Edward Island announced that starting this fall it will also vaccinate boys. Other provinces and territories are under pressure to follow suit, but the high cost of the vaccines is an impediment. A two-dose schedule might shift the cost-benefit analysis in favour of vaccinating boys.
Dobson and his co-authors decided to see if giving HPV vaccine to younger girls could allow provinces and territories to cut the number of doses. The goal, he said, was to see if the very effective immune systems of younger children would respond as well with fewer doses as the immune systems of girls in their late teens and early 30s.
The study used Gardasil, the four-strain vaccine. But other studies have looked at whether two doses of Cervarix would work and have found similar results.
In this study, the researchers randomly assigned 520 girls (aged nine to 13) to receive either three doses of vaccine or two, and then compared their antibody levels to those of 310 older teens and young women (aged 16 to 26) who received three doses of HPV vaccine.
The study is called a non-inferiority study, meaning the researchers were trying to see if the two-dose schedule in girls was non-inferior or not worse than the three-dose regimen in young women. And they found that to be true: Girls had at least as many antibodies at the end of their two-dose program as young women did after three doses.
The young girls who received three doses of vaccine had better antibodies levels than the young girls who got two doses, but Dobson said it's not clear that the extra boost provided by the third shot is needed to protect against HPV infections. As well, it's not clear how long the protection lasts and whether women who have had two or even three doses of the vaccine will need a booster shot (or shots) later in life.
More study and time will answer those questions, Dobson said.
Some answers may come from Quebec, where the province's HPV vaccination program is currently designed to give two doses and then wait five years to see if a third dose is needed. A study is underway there and will be submitted to the provincial health ministry, said Dr. Chantal Sauvageau, a public health specialist with Quebec's Public Health Institute. Sauvageau is also an author on the Dobson study.
Sauvageau cannot talk at this point about what Quebec is seeing. But she said the study that she, Dobson and their colleagues published in JAMA is helping to show a possible path for future use of these vaccines.
"It adds good information. But it has to be put with other information. This study is a good piece, a big piece, but one (piece)," she said.
A commentary published by the journal also called the findings preliminary. Dr. Jessica Kahn and Dr. David Bernstein, of the Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio, said longer followup of the girls who got two doses is needed. They also suggested data on whether a two-dose schedule would work in girls older than 13 would be required before anyone could recommend dropping one dose.
"Using different vaccination schedules for girls younger than 13 years and older than 13 years would not be practical," they wrote.
Dobson noted there is precedent for lowering the number of doses of a vaccine. Vaccines for hepatitis A and B initially followed a three-dose schedule when they were first introduced, but now are given in two doses.
And the vaccine against pneumococcal vaccine, Prevnar, was brought to market as a four-dose vaccine. But a temporary shortage forced some jurisdictions to use a three-dose schedule for a time and it was found to be sufficient to protect children.