As HPV only infects humans, efficacy studies have been performed in animals with analogous papillomaviruses. These studies suggest that the efficacy of L1 virus-like particle vaccines is mediated by the development of a humoral immune response.
The vaccine is prepared from purified virus-like particles of the major capsid L1 protein of HPV types 6, 11, 16 and 18. These HPV types are responsible for approximately:
HPV 16 and 18
- 70% of high-grade cervical dysplasia (CIN 2/3) and adenocarcinoma in situ cases
- 70% of high-grade vulvar dysplasia (VIN 2/3) cases
- a majority of high-grade squamous vaginal lesions
HPV 6 and 11
- 90% of genital wart cases
HPV 6, 11, 16 and 18
- 35–50% of CIN 1 or low-grade cervical dysplasia cases
Up to 80% of sexually active women will become infected with HPV in their lifetime.1 Peak exposure to HPV occurs in late teens and early twenties.2
The efficacy of Gardasil was assessed in four placebo-controlled, double-blind, randomised Phase II and III clinical studies. A total of 20,541 women aged 16–26 years were enrolled and vaccinated without pre-screening for the presence of HPV infection.
Three vaccinations were given over one year scheduled at 0, 2 and 6 months. Efficacy analysis was performed primarily in women naive to the relevant HPV types prior to the first dose and through one month after the final dose (these results are summarised below). In women who were seropositive and/or PCR positive to one or more of the HPV types, there was no evidence of protection from disease caused by these HPV types. However, Gardasil did provide protection against clinical disease caused by the remaining HPV types.
Gardasil demonstrated significant protection benefits against cervical disease. The studies showed 100% efficacy against cervical cancer and high-grade pre-cancerous lesions (CIN 2/3) caused by HPV 16 and 18. The incidence of low-grade cervical lesions (CIN 1) was also significantly reduced. This efficacy was observed up to 4.5 years after completion of the vaccine course.
The studies showed that Gardasil also has benefits beyond the cervix. The vaccine demonstrated 100% efficacy against pre-cancerous vulval lesions (VIN 2/3) caused by HPV 6, 11, 16 and 18. The vaccine also showed 98.9% efficacy against genital warts caused by HPV 6 and 11. Also, a reduction in high-grade vaginal lesions (VaIN 2/3) was observed, although it was not statistically significant.
Overall, 99.9%, 99.8%, 99.8% and 99.6% of women who received Gardasil became anti-HPV 6, anti-HPV 11, anti-HPV 16 and anti-HPV 18 seropositive, respectively, by one month after the third dose.
The vaccine was well tolerated; the most commonly reported adverse events were injection site reactions and mild fever.
1. CDC factsheet on HPV available at www.cdc.gov
2. Data on file. Sanofi Pasteur MSD
Further information: Sanofi Pasteur MSD 01628 785291