Vaccine against cervical cancer passes ''proof of principle''

A recombinant vaccine against the human sexually–transmitted papillomavirus type HPV–16, which is thought to cause as many as half of all cervical cancers, has been shown to prevent long–term HPV–16 infections in a trial with 2400 young women.

This Merck vaccine is the first of what may be several candidates for a vaccine against HPV infections, some prophylactic and some therapeutic, but it has come through with flying colours. Although the trial was designed to measure HPV infection and not cancer, which occurs with only a small percentage of infections, it may prove significant that nine women in the placebo (unvaccinated) group developed clinical lesions — the beginning of cancer — but none did so in the vaccinated group (New England Journal of Medicine 2002;347:1645–51).

Sonia Pagliusi of the WHO Initative for Vaccine Research told the Bulletin ''This is a very interesting vaccine for developing countries as they have 80% of the world's cervical cancer. And they have few other options. They can do the Pap [smear test, requiring cytological observations] but it's not very effective — it's not working. People take the test, but follow–up is difficult''.

According to Andreas Ullrich, who works on national cancer control planning issues at WHO, ''Cervical cancer is a high priority: it's first or second in developing countries, among all cancers.''

Pagliusi added: ''This is the first proof of principle of an HPV vaccine in humans. But it is important to know if the result is relevant to the disease''. So it will be necessary to do larger trials measuring the effect of the vaccine on precancerous lesions. ''HPV is not like HIV — it's only a small percentage of infections that go on to cause cancer.''

Moreover, there are 15 high–risk HPV viruses. Type 16 causes 50% of cases of cervical cancer. Type 18 causes an additional 10–15%; then Types 31, 33, 45 and others account for another 5% or so. An ideal vaccine should cover several virus types. ''But the object of this trial was a proof of principle, which would be more difficult to show with the other viruses because they are relatively rare. You'd need even bigger trials to get a statistical result'' said Pagliusi.

Vaccines are the most cost–effective interventions to prevent life–threatening infections ''And we hope we will need to vaccinate only once in a woman's lifetime, before they become sexually active — with a three–shot course like HepB'' said Pagliusi.

The Merck HPV vaccine is based on the same principle as HepB: a recombinant capsid protein. The trial has so far only measured protection for 1.5 years. But it is a great beginning.

Robert Walgate, Bulletin

World Health Organization Genebra - Genebra - Switzerland