Monograph: |
Human Papilloma Virus Vaccines
Drug Profile
A quadrivalent recombinant human papilloma virus (HPV) vaccine, prepared from purified virus-like particles of the capsid protein L1, is licensed in the USA to prevent genital warts, cervical cancer, and other pre-cancerous lesions caused by HPV types 6, 11, 16, and 18. Further vaccines are under investigation for the treatment or prophylaxis of genital warts and several malignant neoplasms.
The quadrivalent recombinant human papilloma virus vaccine is given in three doses of 0.5 mL intramuscularly. The first dose may be given at any time to girls and women between 9 and 26 years of age; the second dose is given 2 months later, and the third dose 6 months after the first dose.
Malignant neoplasms of the cervix.
More than 99% of cases of cervical cancer diagnosed are associated with the presence of sexually transmitted human papilloma virus DNA and this has prompted the possibility of vaccine development. Viral recombinant proteins are being studied as antigenic components of both prophylactic and therapeutic vaccines. Prophylactic vaccine candidates are based on the recombinant capsid proteins L1 and L2 which self-assemble into virus-like particles which induce antibodies that in turn neutralise the infecting virus. Therapeutic vaccines are based on the viral oncogenic proteins E6 and E7 and are designed to induce cell-mediated immune responses to eliminate infected cells. A prophylactic vaccine is licensed in the USA, while other prophylactic vaccines are in phase III and a further 3 therapeutic vaccine candidates are undergoing phase II evaluation. There is also some preliminary study being conducted into the possibility of a 'chimeric' vaccine combining both prophylactic and therapeutic components, but the immunogenicity and efficacy of such vaccines remains to be established.
For it to be claimed justifiably that a prophylactic vaccine prevents cervical cancer, it is necessary to demonstrate that such a vaccine not only prevents infection but also prevents cancer itself, or at least a defined precursor of disease. Since any placebo-controlled study defining established cancer as an end-point would clearly be unethical, an appropriate compromise is to use the appearance of high-grade dysplasia or pre-cancerous lesions as an end-point, this being regarded as a direct precursor to cervical cancer requiring treatment. However, true pre-cancerous lesions of this kind are relatively unusual in current practice and therefore phase III studies require tens of thousands of subjects in order to establish this efficacy.
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