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Vaccine against cervical cancer virus passes phase 1 trials

BMJ 2001; 322 doi: (Published 03 March 2001) Cite this as: BMJ 2001;322:510
  1. Deborah Josefson
  1. San Francisco

    Women may soon be able to take a vaccine to protect themselves against cervical cancer, one of the most common malignancies to affect women.

    Cervical cancer affects over 400 000 women a year worldwide and results in the death of 200 000 of them. It is caused by infections with oncogenic strains of the human papillomavirus.

    Human papillomavirus is sexually transmitted, and infections are common in both developing and developed countries. Up to 25% of sexually active young women in Canada and the United States are infected with it (Canadian Medical Association Journal 2000;163:503-8).

    In non-industrialised countries, where cervical screening tests are rare, cervical cancer constitutes the most common and lethal of female malignancies. Even in the United States it leads to 5000 deaths a year.

    A vaccine against HPV16, the most prevalent strain of the human papillomavirus found in cervical cancers, has passed phase I clinical trials (Journal of the National Cancer Institute 2001:93:284-92). HPV16 is found in 50% of cervical cancers and HPV types 18, 31, and 45 account for an additional 30% of cervical cancers.

    Led by Dr Clayton Harro from the Johns Hopkins University School of Medicine in Baltimore, Maryland, and Douglas Lowy of the National Institutes of Health, Bethesda, researchers inoculated 72 volunteers aged 18–29 with a prototype vaccine. Fifty eight of the volunteers were women.

    Volunteers were inoculated intramuscularly with either placebo or HPV16 virus-like particles at 0, 1, and 4 months. Both naked vaccine and vaccine with adjuvants were tested. Immune responses were monitored via enzyme linked immunosorbent assays (ELISA) for the presence of IgG antibodies and via HPV virion neutralisation assays.

    The vaccine was constructed around a viral protein, L1, which is responsible for assembling the viral capsid or coat. It comprised the L1 capsid protein devoid of other genes, so that in effect the study subjects were vaccinated with an “empty” virus, eliminating the risk of oncogenicity from the vaccine itself.

    Only subjects deemed at low risk of infection with human papillomavirus were screened, and volunteers were excluded if they had had more than four sexual partners ever or more than two in the previous six months. Six of the 72 volunteers were found to be seropositive for the virus but were none the less included in the study. Exclusion criteria included history of immunodeficiency, abnormal cervical cytology, allergy to vaccine, and current pregnancy or lactation.

    The researchers found that the vaccine elicited a strong immune response, with antibody titres 40 times that seen in natural infections. An immune response was seen by the second month in all cases. Both IgM and IgG titres against HPV16 L1 were raised.

    Peak immunogenicity was seen at the fifth month (one month after receiving the higher dose inoculation), and the adjuvants enhanced the immunogenicity of lower dose vaccines but not the higher dose vaccine.

    All forms of the vaccine were well tolerated, with the most common side effect being pain at the injection site. One subject had transient microscopic haematuria and one experienced a mild rise in liver function tests, which remitted. The work is considered promising, but it remains to be seen if such vaccines will protect against naturally acquired genital infections. Future vaccines will likely be constructed to protect against multiple oncogenic strains.

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