Vaccine development

Researchers are trying to develop a vaccine that could prevent initial infection with the strains of HPV associated with anogenital cancers.

Gardasil, developed by Merck, has been approved in countries including the UK and the US. Over three years, Gardasil caused a 90% decrease in the incidence of persistent infection or disease with these types of HPV, and it was 100% effective against precancerous lesions and genital warts.1,2 Gardasil has also been shown to reduce the risk of developing pre-cancerous cervical lesions caused by ten other types of HPV.3

Both Gardasil and another vaccine, Cervarix, have been most effective as preventive vaccines in women not yet exposed to HPV. Very little therapeutic effect has been seen in those with pre-existing HPV infection. Therefore, the vaccines will probably be most effective if given before people become sexually active.4 Experts have recommended that all girls in the UK between the ages of twelve and thirteen should be vaccinated. As with other sexual health programs including condom use and safer sex promotion, this has been controversial in certain quarters; as well as intimations of encouraging sexual activity, discussions have been raised over issues of cost-effectiveness, patient and family consent, and pharmaceutical interest.

There are currently no recommendations for HPV vaccination for men and boys. However, Gardasil is currently being tested in men for evidence of effects on HPV transmission and anal cancer incidence. Widespread prevalence of anal infection with HPV types 16 and 18 among gay men has led many investigators to suggest that vaccination would be appropriate for gay men.

Another vaccine targeting HPV types 16 and 18, called Cervarix, has been shown to reduce cervical and vaginal infection. The vaccine caused a reduction of new infections with these HPV types by 92% after 27 months, as well as 100% protection against persistent infection and cross-protection against several other HPV types.5 Its manufacturer, Glaxo SmithKline, plans to market the vaccine only to women, and has no plans to investigate the effect of the vaccine in men or in preventing anal disease.

Another HPV 16 virus-like particle (VLP) vaccine has been found, in phase I trials, to stimulate high levels of antibodies and cause only minor side-effects.6 More recent placebo-controlled clinical trials including over 1500 women have shown that this vaccine prevents persistent HPV infection in 94% of women, and is 100% protective against the development of CIN grades 2 and 3 over 36 months.

Other vaccines under development include:

  • A therapeutic vaccine against HPV type 16, being developed by Australian company CSL. The vaccine targets HPV 16 proteins E6 and E7. A dose-ranging study in HIV-positive gay men showed good tolerability and immunologic response to the vaccine, although the study was too small to demonstrate any clear trends in efficacy.7
  • A vaccine which combines preventative and therapeutic effects, by stimulating antibodies against the HPV protein L1, as well as stimulating CD8 T-cells to target the cancer-associated proteins such as E7. To date, studies in mice have provided encouraging results.8
  • A vaccine called SGN-00101 or HspE7, made from the E7 protein of HPV type 16 fused to a protein from a bacterium, has been found to be safe in HIV-positive patients with anal intraepithelial neoplasia (AIN)9. The study found some evidence that the vaccine could be useful in treating the condition, and further studies are underway.9

Vaccine development has focused on the HPV strains 16 and 18, most generally associated with cancerous cell abnormalities. However, recent studies have indicated that other strains, not previously regarded as oncogenic, may also be associated with cervical cancer.10 This may have implications for vaccine development.

References

  1. Garland SM et al. Quadrivalent vaccine against human papillomavirus to prevent anogenital disease. New Eng J Med 356: 1928-1943, 2007
  2. Future II Study Group Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. New Eng J Med 356: 1915-1927, 2007
  3. Brown D et al. HPV type 6/11/16/18 vaccine: first analysis of cross-protection against persistent infection, cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS) caused by oncogenic HPV types in addition to 16/18. 47th ICAAC, Chicago, abstract G-1720b, 2007
  4. Villa LL et al. Prophylactic quadrivalent human papillomavirus (types 6, 11, 16 and 18) L1 virus-like particle vaccine in young women: a randomised double-blind placebo-controlled multicentre phase II efficacy trial. Lancet Oncol 6: 271-278, 2005
  5. Harper DM et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial. Lancet 364: 1757-1765, 2004
  6. Schiller JT et al. Developing HPV virus-like particle vaccines to prevent cervical cancer: a progress report. J Clin Virol 19: 67-74, 2000
  7. Anderson J et al. A randomised, placebo-controlled, dose escalation study to determine the safety, tolerability and immunogenicity of an HPV therapeutic vaccine in HIV-positive participants with oncogenic HPV infection of the anus. Fourth International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 1004, 2003
  8. Gissmann L Papillomavirus-specific vaccines for prevention and treatment of cervical cancer. Eleventh International Congress on Virology, Sydney, abstract 22192, 1998
  9. Palefsky JM et al. A trial of SGN-00101 (HspE7) to treat high-grade anal intraepithelial neoplasia in HIV-positive individuals. AIDS 20: 1151-1155, 2006
  10. Luque AE et al. Prevalence of human papillomavirus genotypes and related abnormalities of cervical cytological results among HIV-1 infected women in Rochester, New York. J Infect Dis 194: 428-434, 2006
This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.