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.
vial or syringe containing 0.5 mL liquid
Approved indication: prevention of human papillomavirus infection and associated genital disease
Australian Medicines Handbook section 20.1
This is the second vaccine to be registered in Australia against human papillomavirus infection and the cancer it can cause. Like the first vaccine (see New drugs, Aust Prescr 2006;29:138-43), this product is not a live vaccine but is made up of virus-like particles derived from the major capsid (L1) protein. It is a bivalent vaccine, designed to protect against human papillomavirus types 16 and 18. These virus types are responsible for around 70% of invasive cervical cancers worldwide and are the most common oncogenic papillomavirus types isolated from Australian women.
The bivalent vaccine has been compared to placebo in a randomised trial of 1113 North American and Brazilian women aged 15–25 years. These women were negative for type 16 or 18 DNA (by the polymerase chain reaction) and seronegative for virus types 16 and 18 at screening. Three doses of the vaccine or placebo were given, at 0, 1 and 6 months. Cervical and cervicovaginal specimens (taken at 3 or 6 month intervals) were analysed for human papillomavirus DNA and abnormal cytology for up to 27 months after the first injection.1
After 27 months, there were four cases of persistent infection with type 16 or 18 human papillomavirus in the vaccinated group (560 women) compared to 31 cases in the placebo group (553 women). Two women in the vaccine group had cytological abnormalities associated with virus type 16 or 18 compared to 27 women in the placebo group.1 These abnormalities included atypical squamous cells of undetermined significance and low- and high-grade squamous intraepithelial lesions.
A follow-up study continued to monitor the women. Some of them were followed in total for approximately 48 months. These women had received all three doses of the vaccine or placebo and their treatment allocation was still double blind. In the follow-up phase, 10 out of 340 women had persistent human papillomavirus type 16 or 18 infection (for 10 months or longer) in the placebo group compared with none of the 357 women in the vaccine group.2
During the combined initial and follow-up phases of the trial, there were four cases of abnormal cytology or histology associated with type 16 or 18 virus in the vaccine group and 83 cases in the placebo group. There were no cases of cervical intraepithelial neoplasia in the vaccine group.2
There seemed to be some cross-protection of the vaccine against infection with other human papillomavirus types, particularly types 45 and 31. This corresponded to fewer cases of cytological and histological abnormalities in the vaccine group compared to the placebo group.2
The vaccine should be given intramuscularly in the deltoid region at 0, 1 and 6 months. The second dose can be delayed for up to 2.5 months after the first dose if necessary. The need for booster doses is currently unknown.
This bivalent vaccine appears to be effective in providing long-term protection against human papillomavirus types 16 and 18 infections and the precancerous lesions associated with them. The previously approved vaccine is quadrivalent and contains antigens from virus types 6, 11, 16 and 18. As human papillomavirus types 6 and 11 cause genital warts, the quadrivalent vaccine is indicated for males and females whereas the bivalent vaccine is only indicated for females, but for a wider age range (10-45 years).
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
Note on references
At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).
- Harper DM, Franco EL, Wheeler C, Ferris DG, Jenkins D, Schuind A, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 2004;364:1757-65.
- Harper DM, Franco EL, Wheeler CM, Moscicki AB, Romanowski B, Roteli-Martins CM, et al. Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet 2006;367:1247-55.