With the licensure of GlaxoSmithKline's human papillomavirus vaccine Cervarix in October, we will soon have two vaccines that prevent cervical cancer in women. But they're not interchangeable, and this could lead to problems.
Cervarix is expected to join Merck's Gardasil on the U.S. market in February 2010. For the first time ever in vaccine history, we will have a situation in which two competing vaccines have very different components and adjuvants that could complicate the decision for practicing physicians—as well as insurers and buying groups—regarding which one to use. I think we need to view human papillomavirus (HPV) vaccines as exceptions to the usual rules of “equivalent and interchangeable” and consider stocking both. Parents should be informed of the features of each vaccine, and the decision to use one or the other should be made with informed consent.
Most clinicians know that both vaccines protect against HPV serotypes 16 and 18, the dominant causes of cervical cancer. But Gardasil also protects against HPV-6 and −11, primarily associated with genital warts, and has recently received approval for use in males, which Cervarix has not. But other differences between the two vaccines are less well recognized, and I believe will turn out to be important.
Although both vaccines are manufactured with similar technology using viruslike particles, Cervarix contains a novel adjuvant, ASO4, that is believed to be responsible for its ability to generate a greater antibody response to HPV-16 and −18, compared with Gardasil. According to a head-to-head comparison conducted by GSK, geometric mean titers of serum neutralizing antibodies ranged from 2.3- to 4.8-fold higher for HPV-16 and 6.8- to 9.1-fold higher for HPV-18 after vaccination with Cervarix, compared with Gardasil, across all ages (Hum. Vaccin. 2009;5:705-19).
Although not proven, we might infer from those data that Cervarix might provide longer-lasting protection against HPV serotypes 16 and 18 and, therefore, a longer duration of time before a booster is needed. Both companies are studying duration of protection with their respective vaccines, and a just-published study showed sustained efficacy and immunogenicity of Cervarix up to 6.4 years (Lancet 2009 Dec. 3 [doi:10.1016/S0140-6736(09)61567-1]). For both vaccines, we should have answers before current vaccinees begin to lose protection.
Both vaccines are indicated for the prevention of cervical cancer and cervical intraepithelial neoplasia (CIN) grades 1–3 due to HPV-16 and −18, and cervical adenocarcinoma in situ. However, Gardasil also has indications for the prevention of vulvar and vaginal intraepithelial neoplasias, which Cervarix does not.
Although not specifically mentioned in Gardasil's label (www.merck.com/product/usa/pi_circulars/g/gardasil/gardasil_pi.pdf
Meanwhile, data included in the label for Cervarix (http://us.gsk.com/products/assets/us_cervarix.pdf
These differences may seem slight, but consider a case in which a young woman who received Gardasil later develops a case of cervical cancer due to HPV-31. Might she be quite upset that she wasn't informed that there was another vaccine that could have prevented it? Conversely, a male or female patient given Cervarix later develops genital warts, or a female develops cervical atypia associated with HPV-6 or −11. Might these patients similarly feel that they were denied the chance to have prevented those outcomes?
Who decides which vaccine is used? In managed care settings, the decision is often made based on cost when vaccines are equivalent, but what about the HPV vaccines where the products are not equivalent?
The same goes for the manufacturer-run vaccine buying groups that offer discounts to increasing numbers of participating physicians who sign contracts that impose strict limits on the amount of vaccine that can be purchased outside of the specified brands.
This has not happened before with vaccines: The two competing brands are not interchangeable. I believe that health plans and vaccine buying groups need to recognize these factors and grant an exception to HPV vaccines.
I think we all should stock both vaccines in our practices, and explain the differences to parents. I plan to distribute pamphlets to patients and families and let them choose, with signatures confirming informed consent. I serve as a consultant to both GSK and Merck & Co. and have shared this information with both companies.
This is going to be complicated.