Vaccines for cervical cancer

Human papillomaviruses (HPVs) are responsible for the nearly 450,000 cervical cancers that occur each year throughout the world. In the United States, the cancer rate is low (13,500 cases per year); nevertheless, HPVs affect millions of men and women annually in the form of genital warts and preinvasive diseases of the cervix and anogenital region. The expense of cancer prevention via precancer and cancer management is high, yet most HPV infections resolve spontaneously as a result of a successful host immune response. Recently, the discovery of methods to reproduce HPV virions (viral-like particles) in vitro has resulted in a successful clinical trial of preventing HPV infection and its associated precursor lesions. Although prevention is type-specific and duration of immunity is unknown, these results validate a vaccine strategy targeting prepubertal children that could prevent a significant proportion of genital warts and cervical precancers and cancers from occurring during reproductive life. Reversing advanced preinvasive and invasive cervical neoplasia with immunotherapeutics is a more difficult challenge, inasmuch as little or no evidence for natural immune-mediated regression of these diseases exists. Nonetheless, recent controlled trials have shown some success in inducing precursor regression with vaccines targeting viral oncoproteins. Anecdotal reports of therapies that augmentcellular immunity raise hopesthattherapeutics targeting multiple pathways of anti-viral or anti-tumor immunity will be beneficial to women with established cervical cancer. However, success will require identifying and circumventing the mechanisms by which tumor cells evade the immune system.