Witnessing protection via the human papillomavirus vaccine
In the next month or so, thousands of girls and boys in their first year of high school across Australia will be nervously lining up to receive a vaccination that will protect them against human papillomavirus – commonly known as HPV.
After three doses of the vaccine, they will have almost 100 per cent protection against the strains of the virus that cause more than 70 per cent of cervical cancers, as well as many cancers of the anus, penis, mouth and throat in men, and genital warts in both sexes.
The vaccinated 12- to 13-year-olds will also become part of one of the country’s most remarkable medical success stories.
It was German researchers who discovered the presence of HPV in cervical tumours in the 1980s, sparking research into the specific types of HPV linked to cervical cancer. With four in five people thought to be exposed to the sexually transmitted virus, the race was on to develop a vaccine.
However, unlike other viruses for which vaccines had been developed, HPV could not be successfully propagated in the laboratory in cell cultures.
Australian clinical immunologist Professor Ian Frazer, working with the late virologist Jian Zhou, developed the technology for producing human papillomavirus-like particles, eliminating the need to grow the virus. His work was the basis for two preventive vaccines – Gardasil, which targets four strains of HPV (HPV 6, 11, 16 and 18), and Cervarix, which targets two strains (HPV 16 and 18). The vaccines have the potential to save an estimated quarter of a million lives annually.
Dr Julia Brotherton, medical director of the National HPV Vaccination Program Register, recalls reading the findings of the first trials that showed the vaccine was 100 per cent effective at preventing the targeted strain of HPV.
“When the first studies came out they were a bit jaw-dropping,” she says.
While there was much optimism about the vaccine’s potential, Brotherton recalls: “I don’t think at the time we imagined we would become a real flagship country for it.”
It was fortuitous timing that saw Australia take the lead in HPV vaccination, she believes.
Professor Frazer was named Australian of the Year in 2006, so was very much in the public eye. The same year, Gardasil was approved for use in Australia.
The stumbling block came when the body that considers which medicines should be publicly funded – the Pharmaceutical Benefits Advisory Committee – knocked back an application to fund a national vaccination program using Gardasil, on the basis that it was not cost effective.
“There was a huge outcry and various people from both sides of parliament were urging action,” Brotherton tells The Saturday Paper. “People wanted the vaccine, and they identified it as an Australian vaccine.”
The debate coincided with Janette Howard, wife of then prime minister John Howard, revealing she was a cervical cancer survivor – not a breast cancer survivor as many had assumed.
After behind-the-scenes negotiations on the vaccine price, John Howard announced in November 2006 that a national vaccination program would be rolled out just five months later.
“There was a confluence of circumstances that led to Australia being on the front foot and staying there,” Brotherton says.
So in April 2007, Australia became the first country to begin a government-funded vaccination program for girls aged 12 to 13 years, with a two-year catch-up program making the vaccine available to all women up to the age of 26.
Six years later, in another world first, boys aged 12 to 13 years were included in the school-based HPV vaccination program. The virus causes about 90 per cent of anal cancers, 35 per cent of penile cancers and 60 per cent of mouth/throat cancers.
By mid-2013, more than 5.3 million doses of the HPV vaccine had been given to school students, with the government funding the program to the tune of $51.1 million in 2013-14.
Australian data demonstrating the vaccination program’s success continues to stack up.
Frazer tells The Saturday Paper: “We are fortunate that the government-sponsored vaccine program has been so successful, with 70 per cent coverage.
“We can already record the disappearance of genital warts in young people, and a sharp reduction in cervical abnormalities amongst young women immunised before the age of 15. We have every reason to expect that this will lead to a corresponding reduction in cervical cancer in due course.”
As cervical cancer usually develops over 10 to 20 years after infection with HPV, the impact on rates of cervical cancer is not likely to emerge for another decade.
However, Victorian girls vaccinated in the school program had an almost 50 per cent reduction in the incidence of high-grade cervical abnormalities (a result that indicates probability of a persistent HPV infection that may develop into cancer if not treated), according to a study published in 2013.
Associate Professor Karen Canfell, chairman of Cancer Council Australia’s Cancer Screening Committee, says the vaccination program outcomes have matched predictions modelled prior to its rollout.
Factors in its success include the high coverage rates of the vaccine in young Australian girls and women compared with other countries, and the wide “catch-up” age range when the program started, says Canfell, of the Lowy Cancer Research Centre at the University of NSW.
“Australia has led the world in implementing a large-scale publicly funded HPV vaccination program,” she says, “and this is already having a dramatic effect in young women.”
But the very success of the vaccination program has led to one concern – despite recommendations women continue with regular Pap smears, recent data shows that those who are vaccinated are less likely to do so.
Brotherton says this is a genuine cause for worry, as many of the women who were vaccinated in the initial cohorts were already sexually active and thus may have been exposed to HPV before vaccination.
“A lot of those women might already have lesions from HPV and we don’t want them to think that can’t occur because they are vaccinated,” she says.
However, a complete overhaul of the cervical cancer screening program is set to be introduced in Australia as early as next year, in response to the vaccine’s success.
“Australia will become one of the first countries to transition from Pap smears to primary HPV screening,” Canfell says.
Rather than a two-yearly Pap smear, which screens for abnormalities in cervical cells, women aged 25-74 years will be tested for HPV every five years. Instead of a recommended 26 Pap smears in a lifetime, women will need nine or 10 HPV tests – a change that is expected to decrease cervical cancer incidence by a further 15 per cent or more, Canfell says. The screening program shake-up is set to be considered by state and territory health ministers within the next few months.
Eventually, the need for cervical screening could be reduced further, as even more effective HPV vaccines become available.
In December, the US Food and Drug Administration approved a new version of the HPV vaccine (Gardasil 9) that protects against an extra five types of cancer-causing HPV, giving it the potential to prevent about 90 per cent of cervical, vulvar, vaginal and anal cancers.
Gardasil 9 is yet to be approved in Australia, but Brotherton says it could become a “game changer”, perhaps reducing the need for women to undergo cervical cancer screening to once or twice in their lifetime.
While HPV vaccines are now available in 120 countries, she admits there is an element of guilt that some neighbouring countries, such as Papua New Guinea, have no cervical cancer screening program and some of the highest rates of cervical cancer in the world.
“I do like to think that our role is perhaps to show what vaccination can do and make it easier to promote the advantages of vaccination in other countries.”
The international vaccine alliance Gavi has now helped make HPV vaccination available in more than 20 developing countries.
“The potential is so huge,” says Brotherton.
Frazer concurs: “The research work by many that led to the vaccine development has paid off in our country – our challenge now is to make sure that the same benefit is seen globally.”
This article was first published in the print edition of The Saturday Paper on Feb 28, 2015 as "Witnessing protection". Subscribe here.