Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Gardasil (Merck Sharp & Dohme)
vials containing 0.5 mL liquid
Approved indication: prevention of human papillomavirus infection and associated genital disease
Australian Medicines Handbook section 20.1
Human papillomavirus is one of the most common sexually transmitted viral infections. While most of these infections are transient, some can persist and lead to the development of cervical cancer. In Australia there are approximately 800 new cases of cervical cancer each year. Cervical screening, which is regularly undertaken by 63% of Australian women, has reduced the mortality associated with cervical cancer due to the early identification and management of precancerous lesions.1
Over 40 different types of human papillomavirus have been identified that infect the genital mucosa. Human papillomavirus types 6 and 11 cause 90% of genital warts. In Australia, the most prevalent types found in invasive cervical cancer are types 16 and 18.1
A quadrivalent human papillomavirus vaccine has been approved in Australia for intramuscular injection in males and females aged 9-15 and in females aged 16-26. This is not a live virus, but contains virus-like particles derived from the major capsid (L1) protein of human papillomavirus types 6, 11, 16 and 18. The vaccine is indicated for the prevention of cervical, vulvar and vaginal cancer, precancerous or dysplastic lesions, genital warts and infection caused by these viral types.
The safety and efficacy of the quadrivalent vaccine has been compared to placebo in one phase II trial and two phase III trials. These trials involved a total of approximately 18 000 women aged 16-26 with a history of normal cervical smears. Participants received three doses of either vaccine or placebo at 0, 2 and 6 months. Human papillomavirus infection and associated genital disease were monitored for up to 36 months after the initial vaccination.
The phase II trial enrolled 552 women from the USA, Europe and Brazil. The efficacy analysis was done on the per-protocol population, which was defined as women who did not have antibodies to vaccine-type human papillomavirus at the beginning of the trial and remained free of infection from vaccine-type human papillomavirus through to completion of the vaccination regimen. At 36 months after the initial dose, 94%, 96%, 100% and 76% of women given the vaccine were seropositive for human papillomavirus vaccine types 6, 11, 16 and 18 respectively. There were 4 cases of persistent vaccine-type human papillomavirus infection or associated genital disease in 235 vaccinated women compared with 36 cases in 233 women in the placebo group, representing a vaccine efficacy of 89%.2
The efficacy of the vaccine appears to be similar in the phase III trials, but as yet the results have not been published in full. In the per-protocol populations, the number of cases of cervical intraepithelial neoplasia or cervical adenocarcinoma in situ was reduced from 80 in 7628 women given the placebo to 4 in 7623 women given the vaccine. Likewise, there was only one case of genital warts, vulval intraepithelial neoplasia or vaginal intraepithelial neoplasia in the vaccine groups compared with 110 cases in the placebo groups. The vaccine did not prevent disease caused by other viral types that were not present in the vaccine.
Although this vaccine is indicated for boys aged 9-15, published evidence of its efficacy in males is lacking.
There were no vaccine-related serious adverse effects reported in the trials. However, there were more injection-site reactions (pain, redness and swelling) and fever in women given the vaccine compared to those given the placebo.
It is likely that this vaccine will reduce human papillomavirus infections, which will in turn reduce cervical cancer and other human papillomavirus-related genital conditions. Men and women are at risk from human papillomavirus infection for as long as they are sexually active. Longer follow-up studies will therefore be needed to assess the duration of efficacy for this quadrivalent vaccine, and to determine whether booster doses will be needed.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Brotherton JML, McIntyre PB. Planning for human papillomavirus vaccines in Australia. Commun Dis Intell 2004;28:249-54. http://www.health.gov.au/internet/wcms/publishing.nsf/Content/cda-pubs-cdi-2004-cdi2802-htm-cdi2802p.htm [cited 2006 Aug 18]
- Villa LL, Costa RLR, Petta CA, Andrade RP, Ault KA, Giuliano AR, et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 2005;6:271-8.