HPV vaccine

Human papilloma virus vaccine.

Although cervical cancer is now relatively uncommon in the UK, world wide it is the second most common cause of cancer related mortality in women. Oncogenic types of human papillomavirus (HPV) DNA are detected in virtually all cervical cancers and persistent infection with oncogenic HPV is the single most important factor in the development of pre-invasive and invasive cancer. HPV is a common sexually transmitted infection, which is usually only transient. Most women will clear the infection spontaneously with no long-term clinical consequences and fewer than 10% of women with a persistent high risk HPV infection will subsequently develop cervical disease. Whilst cervical intra-epithelial neoplasia (CIN) is easily treated conservatively, at present there is no treatment for HPV infection per se.

HPV vaccines may help by preventing HPV infection (immunoprophylaxis) and possibly by treating HPV related disease (immunotherapy). There is ongoing clinical research world wide into HPV vaccines covering a range of applications including prophylaxis in the female and male population and in 'high risk' groups and into the treatment of a spectrum of HPV disease including genital warts, CIN, VIN and invasive cancer. Such strategies could prevent cancer deaths, especially in developing countries where population screening is not feasible and therapeutic options can be limited.

Early results on prophylactic HPV 16 vaccination of young women are very promising and support the hypothesis that prophylactic vaccination will prevent persistent HPV 16 infection. The vaccine appears to be safe and able to produce a significant serological response. An interim analysis of a large double-blinded multicentre randomised controlled trial was reported in 2005 and it is restricted to 1533 (64%) women who meet the criteria of having no serological or DNA evidence of either current or previous HPV 16 infection at enrolment or one month after completing the vaccination regime. The median follow-up of this sub-group was 17.4 months but the final results will require 4 years of follow-up. Of the women receiving the active vaccine, 99.7% seroconverted with mean antibody titre of 1510mMU/ml compared with <6mMU/ml in the placebo arm. There were no serious adverse events reported. Thirty-one women subsequently developed a persistent HPV 16 infection and 9 women a HPV 16 positive CIN lesion. All these women had received placebo. This represents an incidence of persistent HPV 16 infection of 3.8 per 100 woman years for the placebo arm and 0 per 100 women years in the vaccination arm (P, 0.001). There were also 44 cases of CIN negative for HPV16 DNA that were equally distributed between the two trial arms.

So far HPV vaccine results have concentrated on HPV infection but it is fundamental to confirm whether preventing infection will prevent CIN and ultimately reduce deaths from cervical cancer. A public health vaccination programme cannot be directed by sexual behaviour and we need to know the effect of vaccination on a population based cohort. This is paramount in the developing countries with high prevalence and mortality from cervical cancer and where screening is not an option. This will require much larger population based studies with long term follow-up. There are still many questions unanswered such as who should be targeted for vaccination and at what age, how long does immunity last, is there cross cover against other HPV types, who will fund vaccination programmes in particular in developing countries, the benefit of vaccination against women who have already been infected with HPV.