Human Papilloma Virus And a Cervical Cancer Vaccine
Chris - Margaret Stanley is someone from the Department of Pathology at Cambridge University and she's spent a lot of her life working on Human Papilloma Viruses, the viruses that cause warts and verrucas, but they also cause cervical cancer. Tell us about your research.
Margaret - My research has always been asking how does this virus change cells, and more importantly, how can we intervene early in the virus infection to prevent either infection or to prevent the consequences of it.
Chris - How does a virus trigger cancer, because for many people that will be a pretty unusual thing to have said?
Margaret - It's rare. Viruses exist to make more viruses but as part of their life cycle they turn cells on to divide and make DNA. If there is an accident during the virus's replication, when the virus is making its own DNA, and the virus proteins are expressed at the wrong time or in the wrong amount, then they can change the behaviour of the cell. That's basically how this virus causes cancer. It's a rare accident.
Chris - How was it first picked up that this was linked to cervical cancer?
Margaret - That all starts in the 1970s. Everyone's heard of the Pap smear. Well there was a smart cytologist in Canada who realised that some of the cells you saw in the Pap smears were the same types of cells you saw in warts. We'd always assumed from the epidemiology of cervical cancer that it was a disease that had an infectious basis, and so as soon as this was found there was a big effort to find out whether these viruses were involved. The next big step was a German scientist that isolated virus DNA from a cervix cancer, identified what it was and it turned out to be a papilloma virus.
Chris - Was there some anecdotal evidence that nuns were very rare among the bunch of people that got cervical cancer and Jews and Muslims were also very rarely implicated?
Margaret - In essence, you're right. It's an apocryphal story. About 15 000 Belgian nuns were surveyed and only one of these ladies had cervical cancer. Her behaviour before taking the veil was rather extreme.
Chris - So that was a weak link for the nuns. But how did you go about making a vaccine to stop this virus?
Margaret - Again, that was tricky. What you need to do is present the body with the protein that the body first sees with the natural virus infection. In other words, the protein against which you make antibodies. This is actually very difficult for papilloma viruses for all sorts of reasons. Microbiology, recombinant DNA technology, came to the rescue. You isolate the gene that makes the protein of the virus coat. A virus is like and egg: it's got a coat and it's got an interior. So you isolate the gene that makes the protein of the coat and then you express this gene in something like a yeast that grows extraordinarily quickly. As the yeast grows, it expresses the gene and makes the protein, so you make huge amounts of the virus protein. When you make the virus that way, the protein forms its natural shape. In other words, it forms what we call 'the native shape'. It looks like a ball of wool with a set of railway lines. It's the ball of wool that you need for an immune response to be made.
Chris - And at what age is this effective? At what age would you need to challenge someone with this vaccine to guarantee that they're going to be protected?
Margaret - When you immunise someone with a prophylactic or a preventative vaccine, you must give it before they're infected. This is a virus that you acquire as a consequence of sexual activity. I have to say that everybody gets this. This is not a rare virus infection. The only other thing you get as much of with sex is pregnancy so this is very common. So obviously you've got to immunise people before they start having sex. The best age at which to immunise is at childhood. The reason for that is that children make much better antibody responses than adults. I have bad news: as soon as you hit puberty, then immune system goes downhill, so that's why you immunise children. So the optimal age is probably nine or ten.
Chris - Where is it in clinical trials now? It's in humans isn't it?
Margaret - Yes, it's in the large trials called phase three trails and at the moment we've got five year data on about 8000women. I can tell you that it's 100% effective in the women who've been vaccinated.
Chris - So internationally what are the implications?
Margaret - This is the biggest killer from cancer in the Third World. This is a vaccine that prevents infection.
Chris - And I guess, sensitive subject as it is, that this couldn't have been developed with out the use of an animal research model?
Margaret - Absolutely. This has depended on rabbits and dogs because rabbits and dogs were the animals with natural warts and we showed the virus worked there before we went to people.
Chris - So you can actually cure animals and dogs from their own infections if they actually had it?
Margaret - You can indeed.