Completion rates for the three-dose HPV vaccine have been lower than anticipated, but will it weaken the public health benefits of the program? Kate Woods reports.

ON THE 29th of November 2006, the Australian government announced plans to fund a human papillomavirus (HPV) vaccination program.

Aimed at 12-year-old girls, with a catch-up program introduced for girls and women aged 13–26 years, the chosen vaccine, Gardasil (quadrivalent human papillomavirus recombinant vaccine), is administered to participants in a three-dose schedule over a six-month period. 

Both medical and public health professions enthusiastically welcomed the funded program, and it’s easy to understand why. The vaccine promised to prevent more than 90% of genital warts, eliminate at least 70% of cervical cancers and save the lives of up to 300 Australian women annually.

Health economists could also see the benefits to the public purse. Cost-effectiveness analyses suggested that adding the vaccine to the National Cervical Screening Program would be associated with an incremental cost-effectiveness ratio of $51,103 per life-year saved when compared to screening alone.1 This figure was calculated on a number of factors, including the achievement of an 80% coverage rate though a school program involving girls aged from 12 years.

Coverage concerns

Five years on and the early enthusiasm – while still maintained – has been tempered with some concern. Recent data on the performance of the program has revealed we are falling slightly short of the 80% coverage expectation. 

According to the figures, more than four out of five girls (83%) aged 12–13 years in 2007 had received their first HPV vaccine dose by the end of 2009. However, only 80% had received their second dose, and only 73% had received their third and final dose.2

The medical director of the National HPV Vaccination Program Register, Dr Julia Brotherton, admits that higher vaccination coverage within the community would be preferable.

However, she says that these figures are consistent with the uptake of other adolescent vaccines in Australia, and are “very good” compared to other countries such as the US, where only 32% of 12- to 17-year-olds had completed all three doses in 2010.

Positive benefits 

Dr Brotherton is buoyed by Australian data linked to the HPV vaccination program indicating we have already seen a decrease in genital wart presentations among young females (59%) attending sexual health services and among heterosexual men (28%)3 since the program began.

A further study has also reflected a decrease in the incidence of histopathologically defined high-grade cervical abnormalities in Victorian girls younger than 18 years since the introduction of the program.4

“Obviously, the higher the coverage, the better the protection in the community. [But] studies suggest we are seeing herd immunity benefits... already with current coverage rates,” she says.

Dr Brotherton points to a number of reasons that girls are not completing the three-dose course, including being absent from school when the vaccine is due, forgetting and not realising that three doses are needed, or seeing the third dose as a ‘booster’.

“In young women 18–26 years, other common reasons include going travelling or becoming pregnant,” she says. “Another issue may be under-reporting to the register when dose three is missed at school and given in general practice.”

Hopefully, she adds, uptake will continue to improve as the vaccine becomes routine.

Barriers identified 

Associate Professor Rachel Skinner, an adolescent physician at the Children’s Hospital at Westmead and associate professor in the discipline of paediatrics and child health at Sydney University, has been researching the acceptability of the HPV vaccine for a number of years.

She says as well as understanding the reasons young girls do not complete the three-dose course, we need to uncover the barriers stopping them from actually commencing the course if we want to improve uptake. 

“Our research shows that one of the main barriers is lack of knowledge,” she says. 

“Parents don’t really have a great understanding of what the vaccine does, how it works or what it even prevents.

“Similarly, young people often don’t know why they are being vaccinated; many parents are not discussing the issue with them, teachers don’t have any information, and the nurses are often busy vaccinating and so don’t have time to answer questions in much detail.”

Due to this lack of knowledge, Professor Skinner says myths such as ‘the vaccine has a cancer in it’ and ‘it is an extraordinarily painful vaccine’ have developed, leading to fear and anxiety among adolescents and, in turn, refusal of the vaccine.

The other major barrier, says Professor Skinner, is consent.

Parents must provide written consent for vaccination as well as consent for notification of vaccination to the HPV vaccine register and linkage to state cervical cytology and cancer registers.

She says these forms, which are given to children to take home, are too often lost or forgotten.

“One way to overcome this problem may be to consider the way the vaccine is given overseas,” she explains.

“In the UK, young people don’t need parental consent. Instead, a nurse assesses the young person’s understanding of the risks and benefits and gives the vaccine when they believe the young person has the maturity to understand the implications of their decision.

“They also have a very good educational program, and I think both these reasons are why they have an uptake level of above 80%.” 

Dr Skinner adds that Denmark also has a high uptake, but this is because they are able to link vaccination status to national identification numbers and send reminders to patients.

“I don’t believe that our 70% uptake is reflective of parents or adolescents not wanting to be vaccinated. I think it is more reflective of the need to improve our logistical processes and the education and information available about the vaccine.”

She said a number of different strategies aimed at improving these two areas are currently being trialled.

“We are on track, we just need to think carefully about the best ways to move forward.”  

Early data on two doses

Professor Ian Frazer is the research director at the Translational Research Institute in Brisbane and inventor of the HPV vaccine.

He is not too concerned with current coverage rates, saying two HPV vaccinations do provide women with some degree of protection against the infection.

“The little bit of data we do have suggests two shots gives good protection at least in the short to middle term, and there are several big studies underway in India and Canada looking at whether this is true in the long term also,” he says.

While Professor Frazer says he would not recommend women have only two of the three vaccinations based on the current evidence, our knowledge of ‘risk of infection’, combined with data on the long-term durability and effectiveness of two doses, may change this in the future.

“[HPV] is a virus that women are much more likely to get when they first become sexually active. 

“By the time 10, 15 years has passed, risk of infection has fallen substantially because women are now less likely to indulge in the activities that would have given them the infection in the first place.

“So it may not matter very much if you don’t get lifelong protection. It may be that two shots will turn out just fine in terms of protecting the community.”

Particularly if we also begin immunising boys, he adds.

“All vaccination programs work on the basis that you get as many eligible people as you can, accepting that for one reason or another that this will not include everyone,” he says.

“If you get the majority – boys as well as girls – then the people who have missed out will also become protected by virtue of the fact that virus is not being passed on anymore. That is the great thing about vaccination programs.”

Media stories fuel anxiety

NEGATIVE media reports relating to the safety of the HPV vaccine have continually undermined community confidence in the school-based vaccination program over recent years.

Shortly after it commenced in 2007, negative media reports emerged after 26 girls experienced dizziness, syncope and/or neurological symptoms within two hours of being immunised at a Melbourne school.5

An investigation later revealed symptoms were due to a psychogenic response to mass vaccination in a school setting.

“Of significance was the fact that key opinion leaders and the minister for health rapidly stated ongoing confidence in the vaccine program, and the program was not interrupted,” according to a recent review article.5

The negative reports continued in 2009 after a JAMA article reported that almost 12,500 vaccine recipients experienced mild to serious side-effects after receiving Gardasil, and then again after a 14-year-old girl died within hours of receiving an HPV vaccine in Britain. 

An autopsy later uncovered that an undiag­nosed malignant tumour was to blame.

Dr Julia Brotherton, medical director of the National HPV Vaccination Program Register, says while it is hard to say whether adverse media stories have stopped girls from completing their vaccine course, vaccine providers and schools are very aware of the issue.

“School programs across Australia have guidelines in place to minimise anxiety amongst students and reduce the chance of ‘hysterical’ reactions,” she says.