Cervical cancer affects nearly half a million women a year worldwide, and has a mortality rate of 50 per cent. The greatest problem is in the developing world, but almost 3,000 women are diagnosed annually in the UK alone.
Infection occurs with certain types of the sexually transmitted human papillomavirus (HPV), in particular HPV 16 and HPV 18. It has been shown that 99.7 per cent of cervical cancers contain HPV DNA.
Infection with HPV appears to be extremely common in young people, but is usually transient. The presence of HPV seems to cause more problems in women who have persistent infection and are over the age of 30.
Developing the vaccine
Screening tests are a way of detecting cellular abnormalities early, but the ultimate solution to a viral disease is a vaccine.
Most viral vaccines are based on an attenuated form of the virus, but this has been difficult with HPV because there is no effective culture system.
The answer has been to manufacture virus-like particles (VLPs) using the L1 and/or L2 virus coat proteins. VLPs have the outward appearance of the virus and generate a powerful immune response, but are harmless as they contain no DNA.
Another problem is that there are potentially 15 different cervical cancer HPV types to be incorporated. However, two prophylactic vaccines have proved extremely effective in clinical trials. One of these, Gardasil, contains all four HPV types and protects against genital warts (types 6 and 11) as well as the most common cervical cancers (types 16 and 18).
The other, Cervarix, contains types 16 and 18, and thus targets only cervical cancer.
Clinical trials have demonstrated 100 per cent efficacy against persistent HPV infection and development of cervical intraepithelial neoplasia after four and a half years of follow-up.
Recent data suggest a degree of cross-protection against HPV types 31 and 45, which are phylogenetically related to 16 and 18. This would significantly increase the protection afforded by the vaccines.
The HPV virus is very successful at avoiding the host immune system, so natural immunity is poor. Both vaccines, however, result in antibody titres that are 60 to 100 times higher than those generated by natural infection and persist for longer (10–16 times higher after four and a half years). The effect is thought to be caused by an adjuvant present in the vaccine.
The strength of the immune response produced by the vaccines could vary because they contain different adjuvants.
Gardasil is available in the UK now. It is expected that Cervarix will be approved in spring 2007.
A number of questions remain, however. It would seem logical to administer the HPV vaccine with other childhood vaccines, in order to remove any link with sexual activity in the minds of parents. But we do not know at present how long the immunity lasts and this method will depend on immunity lasting for decades, or on boosters being given.
It is currently envisaged that girls aged between 11 and 12 would be the target. But should we not vaccinate boys as well?
Cost-effectiveness is increasingly discussed. Studies are under way to evaluate the benefit of vaccinating previously infected women over 25 years old, with the aim of preventing not only reinfection, but also persistence of infection.
If these are successful, vaccination of a wider age range should be considered in order to have more immediate impact on cervical cancer rates.
A key question is the potential resistance to an HPV vaccine because of lack of education about HPV among both the public and health professionals. Possibly the most important aspect will be how the information is presented, and work needs to be done on finding the most effective way of doing this.
Other questions need to be considered. If we eliminate cancer due to HPV types 16 and 18, will other types take their place? Will we need different vaccines for different populations?
However, at least one generation of women will continue to require screening.
The number of HPV types incorporated in the vaccine must increase in order to eliminate all cervical cancers.
Thus, an important message is that even after the introduction of the vaccine, cervical screening will need to continue, certainly for women who have not been vaccinated before the onset of sexual activity, but in any case, for at least the next 20 years, to assess the longevity of immunity conferred.
Dr Szarewski is clinical consultant and honorary senior lecturer at the Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, London
This is an edited version of an article published in MIMS Women’s Health. To receive MIMS Women’s Health visit www.hayreg.co.uk/specials
Key points on HPV vaccination
- A nationwide vaccination programme targeted at young girls against HPV would confer huge health benefits.
- We do not know at present how long the immunity conferred by these vaccines lasts.
- This method of administration would depend on the immunity lasting for decades, or on boosters being given.
- Lack of education of both public and health professionals could contribute to the potential resistance to an HPV vaccine.
- Cervical screening would have to continue for at least 20 years.
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