Prophylactic HPV vaccines – an update

Abstract

Cervical cancer affects nearly half a million women each year, and nearly half of them die. The greatest problem is in the developing world, though even in the UK nearly 3 000 women develop cervical cancer each year.Infection with certain types of sexually transmitted human papillomavirus (HPV), in particular HPV 16 and HPV 18, is the main cause of cervical cancer. It has been shown that 99.7% of cervical cancers contain HPV DNA. Infection with HPV appears to be extremely common in young people, but is usually transient. It appears that the presence of HPV is more meaningful in older women (over 30), who have persistent infection.Screening tests detect cellular abnormalities early, but the ultimate solution to a viral disease is obviously a vaccine. A problem is the number of cervical cancer HPV types which need to be included (potentially 15). Two vaccines have proved extremely effective in clinical trials, with recent results demonstrating 100% efficacy against persistent HPV infection and development of CIN up to five years of follow up (Harper 2006, Villa 2005). One of these (Gardasil, recently licensed) contains four HPV types and would thus protect against genital warts (types 6 and 11) as well as the commonest cervical cancer HPV types (16 and 18). Gardasil®is licensed for children and adolescents aged 9 to15 years and adult females aged 16 to 26 years. The NHS cost of one dose of the vaccine is £80.50, three doses are required to provide protection.In clinical trials Gardasil® showed 100% (95% CI 92.9 – 100) efficacy in the prevention of CIN2/3 related to HPV 16 and 18. Gardasil® was also 100% (95% CI 41.4 – 100) effective in preventing VIN2/3 related to HPV 16 and 18. In addition, there were no cases of high‐grade vaginal lesions (VaIN2/3) due to HPV types 16 and 18 in those who received Gardasil®, compared to five in those who received placebo (not statistically significant). Gardasil has shown 98.9% (95% CI 93.7–100) efficacy in the prevention of genital warts related to HPV types 6 and 11 (Siddiqui & Perry, 2006).The other vaccine (Cervarix) contains types 16 and 18, and thus targets cervical cancer alone. Recent data (Harper 2006) have suggested a degree of cross‐protection, against HPV types 31 and 45, which are phylogenetically related to types 16 and 18. If confirmed, this would significantly increase the level of protection afforded by the vaccines.There are still a number of questions to which we do not have answers. We do not know at present how long the immunity conferred by these vaccines lasts: ideally, such a vaccine would be administered with other childhood vaccines, removing any link with sexual activity in the minds of parents. However, that would depend on the immunity lasting for decades, or boosters being given. At present, it is envisaged that the age group between 11 and 12 is probably going to be the target, and indeed, this is what has been recommended in the US. But should we not vaccinate boys as well as girls?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? What might be the effect of a vaccine in HIV positive women? There are no answers to these questions at present.A fundamental issue underpinning the potential resistance to an HPV vaccine is the lack of education of both the public and health professionals about HPV. Possibly the most important aspect will be how the information is presented, and work needs to be done to ascertain the most effective ways of doing this. This has been a woefully neglected aspect of strategies proposed for the introduction both of HPV testing and vaccines.In theory, an HPV vaccine could prevent almost all cervical cancer, eventually removing the need for cervical smears. However, there is at least one whole generation of women for whom the vaccine will come too late, and who will continue to require screening. Also, until the number of HPV types in the vaccine is increased, there will still be cancers not prevented by vaccination. The exact point at which vaccination supersedes screening will depend upon the percentage of cancers preventable by the vaccine, the percentage being prevented by the screening programme in place, the attitude of women to having smears and the attitude of the society in which they live to vaccination against a sexually transmitted virus. It is therefore clear this will vary considerably.