Faculty of 1000

Post-publication peer review

Fitter healthier

Posted by rpg on 14 January, 2010

The necessary length of time from an initial scientific breakthrough to a tried and tested application, clinical or otherwise, can often tarnish the initial thrill of that first result, or even make you forget about it altogether. I have a photograph of my then three year old daughter sitting on the breakfast bar in the kitchen in our house in Cambridge, ‘reading’ the edition of Nature in which the first draft of the Human Genome sequence was published. It struck me, then, that I remembered the debate about whether we should sequence the genome, over ten years previously; and there we were, with the answer in our hands. (I still have that copy of Nature, as well as a New Scientist from when I was at high school which laid out the arguments for and against. I intend to blog about that elsewhere.)

Twelve years ago (check out that old-time BBC retro goodness!), the BBC carried a story that carried hope for a vaccine against cervical cancer:

Scientists believe they are on the verge of creating a vaccine to combat some forms of cancer.

It is hoped eventually the vaccine could be used on children.

Just half a year later the BBC again carried a story, this time with news of promising trials:

Scientists in Britain and the United States say they have made a breakthrough in finding a vaccine for cervical cancer which kills about a quarter of a million women throughout the world every year.
The scientists, in Manchester and Georgia, say trials on animals indicate that it could provide immunity to the virus which is responsible for ninety-five per-cent of cervical cancers in humans.

However it is expected to take about ten years of such trails and tests before a final judgement on its effectiveness can be made.

Worldwide, there are about 500,000 new cases of cervical cancer each year, and about a quarter of a million deaths from it. In developing countries (where nearly 80% of new cases occur), it is the most lethal form of cancer, and is responsible for one in ten cancer-related deaths globally. Compared with other cancers, it disproportionally affects younger women, causing substantial societal effects. An effective vaccine is therefore high on the wishlist for a lot of people.

Developing countries suffer highest cervical cancer mortality rates
Mortality rates per 100k from cervical cancer

Rather splendidly, then, just this week we published an evaluation of a paper in The Lancet describing the long-term efficacy of such a vaccination in a double-blind randomized control trial. The efficacy of the combined Human Papilloma Virus (HPV)-16/18 vaccine has already been demonstrated, having been ‘robustly’ estimated at 98%, but in the current paper it hits 100%*. Now that’s truly remarkable, but we need to realize that this was not a huge trial (n=349 in efficacy cohort, 340 in placebo), and so it lacks some statistical power. But perhaps more important than its efficacy, especially for developing countries where the cost and complexity of  booster vaccinations might be prohibitive, the long-term immune response turns out to be pretty outstanding, too.

Because the vaccine should be given to virgins (it is prophylactic; it does not protect against an existing infection), it has to be given to reasonably young girls, and needs (ideally) to last them throughout their sexually active life (which means until death, effectively). The current study only tracks women for six years four months, which you might think isn’t very long at all. However, after an early (in the first ~18 months) drop off in antibody titre the IgG antibody concentration remained stable in the vaccine group. The trial was not powerful enough (that is, not enough ‘accrued events’—i.e. neoplasms—occurred in the placebo group) to detect a small waning of efficacy over an extended period. Nonetheless, there is good reason to suspect the vaccination will remain effective for another ten years at least.

The HPV-16/18 vaccine is also safe—there was no significant difference in recorded events between vaccinated and placebo cohorts. Indeed, there were slightly more adverse events in the placebo group, and in a previous study, three women in the placebo cohort withdrew due to a non-serious adverse event; and the only withdrawal from the experimental cohort was due to a spontaneous (non-vaccine related) abortion.

Just before Christmas my daughter—the same one who sat in my kitchen with Nature—came home from school with a consent form. She got her first HPV jab soon after.

Score one more for science.

*that is, it’s 100% effective against the 70% of cancers caused by HPV 16 and 18.

The GlaxoSmithKline Vaccine HPV-007 Study Group (2009). Sustained efficacy and immunogenicity of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine: analysis of a randomised placebo-controlled trial up to 6·4 years The Lancet, 374 (9706), 1975-1985 DOI: 10.1016/S0140-6736(09)61567-1

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2 Responses to “Fitter healthier”

  1. NHY said

    You will enjoy reading the award- winning book “The HPV Vaccine Controversy: Sex, Cancer, God and Politics ? It is authored by Shobha S. Krishnan, M.D, Barnard college, Columbia University. The book is written without the influence of any pharmaceutical companies or special interest groups. It is available at amazon.com and Barnes and Noble .com but you can also get it through your local library or request them to get it for you. It educates both professionals and the public about HPV infections, the diseases they cause and the role/ controversies surrounding the new vaccines. The book has been chosen as one of the most valuable books of 2009 and is the recipient of The Book of The Year 2009 Award. The Journal of the American Medical Association (JAMA, June 17th 2009) calls the book superb and a terrific contribution to the field. Website: http://www.thehpvbook.com/ – don’t miss it!

  2. rpg said

    Sounds interesting. Any chance of a review copy?

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