Pharmacology Update
Human Papillomavirus Quadrivalent (types 6, 11, 16, 18) Recombinant Vaccine (Gardasil®)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD, Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco; Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationships to this field of study.
The FDA has licensed the first vaccine to prevent cancer due to human papillomaviruses (HPV) types 6, 11, 16, and 18, the most common subtypes of this prevalent virus. The vaccine represents the first vaccine approved for the prevention of cancer. The quadrivalent vaccine is marketed by Merck & Co. as Gardasil®.
Indications
HPV vaccine is indicated in girls and women (age 9- 26 yrs) for the prevention of cervical cancer, genital warts, and precancerous or dysplastic lesions (cervical adenocarcinoma in situ (AIS), cervical intraepithelial neoplasia (CIN) grade 2 and 3, vulvar intraepithelial neoplasia (VIN) grade 2 and 3, vaginal intraepithelial neoplasia (VaIN) grade 2 and 3 and cervical intraepithelial neoplasia grade 1.1
Dosage
0.5 mL is administered intramuscularly in 3 separate doses over 6 months (0, 2, 6 months).
Potential Advantages
The vaccine has demonstrated effectiveness in preventing HPV infection, cervical dysplasia, and external genital lesions related to the 4 types of HPV.1-3 Studies were not long enough (~ 2 yrs) for cervical cancer to develop.4
Potential Disadvantages
The vaccine is not effective treatment for individuals who have already been infected with HPV (ie, PCR or seropositive) and does not protect against HPV types not included in the vaccine. The duration of immunity beyond 2 years has not been established. The most common adverse events are local injection site reactions—pain (84%), swelling (25%), erythema (25%), and fever (10%).1
Comments
The HPV vaccine is comprised of virus-like particles (VLP) derived from the L1 capsoid protein of HPV types 6, 11, 16, 18 using recombinant techniques. Each dose (0.5 mL) contains 20 μg, 40 μg, 40 μg, and 20 μg of VLPs respectively. The efficacy of HPV vaccine was established in four studies with 3 involving all four HPV types 6, 11, 16, and 18 (n ~ 18,000). Subjects were nonpregnant women ages 16-23. Combined efficacy in preventing AIS, CIN 1, 2, or 3 were 95.2% (95% CI, 87.2%-98.7%) and 98.9% (95% CI, 93.7%-100%) for genital warts in individuals who received all 3 doses and were PCR or seronegative at baseline and one month after the last dose.1 For those who received at least one dose, were HPV-naïve at baseline and 1 month after the first dose, the efficacies were 93.7% (95% CI, 87.7%-97.2%) and 93.4% (95% CI, 87.0%-97.0%) respectively. For the general population (HPV-naïve and nonnaive) under the same conditions, efficacies dropped to 46.4% (95% CI, 35.2%-55.7%) and 68.5% (95% CI, 57.5%-77.0%). The vaccine is only effective against types in the vaccine to which the patient is naïve. The vaccine appears to be as effective in young women and adolescents based on immune response. The vaccine is generally well tolerated with local injection reactions most frequently reported. The estimated cost for Gardasil is $360 per person.
Clinical Implications
HPV is a common infection among sexually active women as up to 70% of sexually active women may become infected in their lifetime.5 The American Cancer Society estimates that in 2006 there will be about 9,710 new cases of cervical cancer and about 3,700 will die from the disease.6 HPV types 16 and 18 causes approximately 70% of cervical cancers and types 6 and 11, 90% of genital warts.4 The vaccine is most effective when administered to HPV-naïve individuals (eg, before start of sexual activity). The Advisory Committee on Immunization Practices (ACIP) recommends HPV vaccine for females at age 11 to 12 years of age.7 Catch up vaccination is also recommended for females 13 through 18 years of age who have not been previously vaccinated or who have not completed the full series. The vaccine does not protect against less common HPV types not included in the vaccine. Therefore routine and regular pap screening must not be ignored.
References
1. Gardasil® Product Information. Merck & Co. June, 2006.
2. Siddiqui MA, Perry CM. Human papillomavirus quadrivalent (types 6, 11, 16, 18) recombinant vaccine (Gardasil). Drugs. 2006;66:1263-1271.
3. Villa LL, et al. Immunologic responses following administration of a vaccine targeting human papillomavirus Types 6, 11, 16, and 18. Vaccine. 2006;24:5571-5583.
4. FDA News June 8, 2006. http://www.fda.gov/bbs/topics/NEWS/2006/NEW01385.html. Accessed 7/28/06.
5. Bosch FX, de Sanjose S. Chapter 1: Human papillomavirus and cervical cancer—burden and assessment of causality. J Natl Cancer Inst Monogr. 2003,31:3-13.
6. www.cancer.org/docroot/home/index.asp. Accessed 8/2/06.
7. www.cdc.gov/nip/acip. Accessed 8/8/06.
The FDA has licensed the first vaccine to prevent cancer due to human papillomaviruses (HPV) types 6, 11, 16, and 18, the most common subtypes of this prevalent virus.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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