The results of two Phase III clinical trials published in the New England Journal of Medicine report that the HPV vaccine Gardasil® (Quadrivalent Human Papillomavirus [Types 6, 11, 16, 18] Recombinant Vaccine) has high efficacy when given to girls and women who are not already infected with HPV.
Human papillomaviruses (HPV) consist of more than 100 different viruses. Some types of HPV cause warts on the hands or feet; others cause genital warts; and some have been linked with cancer, most notably cervical cancer. The types of HPV most commonly linked with cervical cancer are HPV 16 and HPV 18, but several other high-risk types contribute to cancer as well.
The types of HPV that cause cervical cancer or genital warts are transmitted sexually. HPV infection is extremely common and generally occurs soon after an individual becomes sexually active. Although most infections resolve on their own, some persist and can lead to precancerous or cancerous changes to the cervix, vulva, vagina, penis, and anus.
Vaccines that prevent infection with high-risk types of HPV have the potential to greatly reduce the occurrence of cervical cancer. The HPV vaccine that is currently on the market is Gardasil®, which targets HPV types 6 and 11 (which are linked with genital warts) as well as the cancer-associated types 16 and 18. Another HPV vaccine that may be approved is Cervarix™, which targets HPV types 16 and 18 only. Because HPV types 16 and 18 are thought to account for roughly 70% of all cases of cervical cancer, widespread use of these vaccines would have the potential to eliminate most (but not all) cases of cervical cancer.
The efficacy of Gardasil against external genital warts and abnormalities and precancers of the cervix, vulva, and vagina was evaluated by a Phase III clinical trial known as FUTURE I. The study enrolled more than 5,000 women between the ages of 16 and 24 years. Study participants have now been followed for an average of three years.
- Among women who were not infected with HPV types 6, 11, 16, or 18 at the start of the study, Gardasil provided 100% protection against cervical, vulvar, or vaginal changes linked with these types of HPV.
- Among all study participants (including those who were already infected with HPV at the start of the study), vaccine efficacy was lower; efficacy against cervical changes due to HPV types 6, 11, 16, or 18 was 55%. Efficacy against cervical changes due to any type of HPV infection was 20%.
A second Phase III clinical trial, known as FUTURE II, evaluated the efficacy of Gardasil against high-grade precancerous changes to the cervix. FUTURE II enrolled more than 12,000 women between the ages of 15 and 26 years. Study participants have been followed for an average of three years.
- Among women who were not infected with HPV types 16 or 18 at the start of the study, Gardasil provided 98% protection against high-grade cervical precancers linked with these types of HPV.
- Among all study participants (including those who were already infected with HPV at the start of the study), the efficacy of Gardasil against cervical precancers due to HPV types 16 or 18 was 44%. Efficacy against cervical precancers due to any type of HPV was 17%.
These studies indicate that vaccine effectiveness is high when the vaccine is given prior to HPV exposure. This highlights the importance of vaccinating girls before they become sexually active. These studies also offer a reminder that the vaccine does not protect against all types of HPV, and that cervical cancer screening remains important following vaccination.
An editorial that accompanies these two studies notes, “On the one hand, the vaccine has high efficacy against certain HPV types that cause life-threatening disease, and it appears to be safe; delaying vaccination may mean that many women will miss an opportunity for long-lasting protection. On the other hand, a cautious approach may be warranted in light of important unanswered questions about overall vaccine effectiveness, duration of protection, and adverse effects that may emerge over time.”