How will HPV vaccines affect cervical cancer?

Abstract

Cervical cancer is the second largest cause of cancer deaths in women worldwide. Persistent infection with human papillomavirus (HPV) is necessary but not sufficient to cause cervical cancer, and preventing HPV infection can prevent the disease. Cervical cancer is currently prevented by Pap smears and/or HPV testing and ablation of high-grade squamous intraepithelial lesions (HSILs). However, the US Food and Drug Administration approved a preventive HPV vaccine on 8 June 2006 for the immunization of women between 9–26 years of age. HPV virus-like particle (VLP) vaccines based on the major capsid antigen L1 show very high protective efficacy and good safety profiles so far, and therefore have the potential to globally affect cervical cancer. However, guidelines on when to vaccinate and whether a boost is necessary depend on the duration of protection, which remains to be determined. Protection with the L1 VLP vaccine shows strong HPV type restriction, therefore highly valent vaccines are required for broad protection. Minor capsid antigen L2-based vaccines might have potential for broad coverage with a monovalent vaccine. There is little evidence that HPV VLP vaccines have therapeutic activity in patients, and the continued development of therapeutic vaccines is warranted. The influence of herd immunity through the vaccination of men is likely to be beneficial, but it will have a relatively modest effect on cervical cancer rates compared with the broad vaccination of women. However, trials to evaluate the HPV vaccine in men are ongoing, as men do contract genital warts and HPV-related cancers at other sites in addition to transmitting HPV to women. Societal response is developing and will have an effect on the introduction of HPV vaccines. Cervical cancer normally occurs in developing countries that lack the resources for screening. The development of alternative HPV vaccines that are low cost and heat stable will be important for the worldwide introduction of the vaccine. Approaches to needle-free vaccination are also being tested. Immunodeficient patients suffer more severe HPV disease and have greater susceptibility to HPV-related cancer. It is important to determine whether these patients will respond less well to HPV vaccines.