IARC 50th Anniversary Conference

Halving cancer mortality

Prof Richard Peto - University of Oxford, Oxford, England

You are addressing the issue of halving cancer mortality, how are you tackling this?

Several big issues: there’s prevention, there’s treatment. Now, on prevention the key thing still is tobacco. Thirty years ago when we were writing about the causes of cancer in the United States we said that about 30% of all US cancer deaths were due to tobacco, that was far more than the sum of all the other reliably known causes put together. In the United States that proportion rose a bit then fell a bit but it’s still around 30%, so that figure is still about true but the difference is that in those days tobacco deaths were rising, now tobacco deaths are falling but still it’s 30%. In the United Kingdom a quarter of all cancer deaths are due to smoking; in the European Union the same is true. The governments are taking smoking seriously now and the British government has just passed laws that all cigarettes have got to be sold in plain packages, let’s hope many other countries do similarly. But we’ve got to take this seriously and we’re going to have to continue to take it seriously for many decades. In 2050 smoking is still going to be one of the main causes of cancer, the main causes of premature death in rich countries. People talk now about we’re now into the tobacco endgame, well in many places it’s not ending and it’s not a game.

In which countries is tobacco consumption increasing?

Take China, that’s the most important example. There are 300 million smokers; Chinese men constitute 8% of the world’s population but they smoke 40% of the world’s cigarettes. Back in 1990 cigarettes were causing 10% of all deaths, all deaths from all causes in Chinese men, now it’s 20% and by the 2030s it’s going to be about 30%. Now, you put that increase from 20% of all male deaths to 30% of all male deaths, you put that together with the increase in population that is taking place in China and you’re going to go from about a million deaths from smoking now in China to two million by the 2030s and three million by mid-century, just if present patterns continue. Of course if the women start smoking then there will be that added to it as well. But mainly it’s the men.

Smoking is actively being promoted in emerging countries too.

I think if we see it just as a question of tobacco industry villainy then we’re actually missing the point. This is addictive – Russia, China, Eastern Europe, there was no tobacco industry advertising and yet you’ve got two-thirds of the men smoking. So it’s not just a question of industry villainy, I think you’ve got to say why is it that people smoke? How can we help explain the risks and how can we help people to escape from those risks?

Aside from tobacco, what other causes of cancer can be prevented?

The obvious things are the infections, the human papilloma virus infections, hepatitis B, H. pylori for stomach cancer, although it’s not quite so obvious how to really reduce exposure to that. We have vaccines against those viruses at least, against hepatitis B and against the most important types of human papilloma virus and these vaccines are being used – hepatitis B vaccination is now getting about 80% coverage worldwide, 80% is wonderful. And human papilloma virus, HPV vaccine, isn’t yet up at those levels of coverage but it could be. So we can vaccinate but the thing is you’re vaccinating either in infancy, in the case of HBV, or in childhood for HPV, against deaths from cancer in middle and old age. So these vaccination campaigns will have a big effect on cancer mortality in the second half of this century but they will not have a big effect on cancer mortality in this half of the century. Again with smoking, if we hear kids not to smoke that’s great, it will reduce cancer deaths in the second half of this century but not the first half of this century. If we want to reduce, if we want to avoid large numbers of the 300 million or so tobacco deaths this side of 2050 we’ve got to get those who now smoke to stop. The key thing on that, well one of the key things, is price. At the moment the governments of the world make $300 billion per year in either profits on making cigarettes or taxes on the sale of cigarettes. So the governments of the world make $300 billion a year. Now this is not big money for governments, it’s reasonably big money but not enormous. They lent $700 billion to try and bail out the banks in the big crash, so it’s big enough to be interesting though. If the World Health Organisation achieves its aim of a one-third reduction in tobacco consumption by either 2025 or 2030, they’ve been two separate goals, but the aim anyway is a one-third reduction. Now, if prices stay the same and tobacco sales go down by a third, the governments of the world lose $100 billion. But if you double, if you increase excise taxes on tobacco so that prices increase substantially, you’re doubling the overall price of tobacco by means of excise taxes, then that alone would reduce consumption by a third but in that circumstance the governments of the world would gain $100 billion.. Now, I don’t believe that the governments of the world are really going to encourage the loss of $100 billion but I do think they could be persuaded to accept $100 billion by doubling the price.

In regards to treatment, how do you propose to halve cancer mortality?

Obviously in treatment, because we’re sequencing the cancers now and we’re understanding the mechanisms, it might be we’re going to get very specific treatments for very specific cellular abnormalities. That could well happen and the best example of this is an anti-cancer drug that got invented fifty years too early, which is tamoxifen. Now, it’s a 21st century drug, it takes a particular mechanism in the cancer cell, blocks it and then has a huge effect on long-term survival. If you just give five years of tamoxifen, which is out of patent and for most women is really quite tolerable although some get side effects that really are uncomfortable, then you can reduce the fifteen year risk of death from breast cancer by about a third. And it seems now that if you use slightly different endocrine treatments, which are also out of patent now, aromatase inhibitors, then these have a slightly greater anti-breast cancer effect even than tamoxifen. And it seems in both cases that if you continue beyond five years of treatment then it seems as though ten years of treatment with endocrine therapy will substantially reduce twenty year cancer mortality. And chemotherapy for breast cancer, simple chemotherapy, not very complicated chemotherapy, surgery, accurate surgery, and we can make surgery more accurate and then radiotherapy, if you’ve done breast conserving surgery you do need to give radiotherapy to the conserved breast otherwise you’re at quite a risk of local recurrence, these things, better local control and quite cheap systemic drugs, actually have in total reduced British breast cancer mortality by more than half since 1990. So if you say what’s the probability that a British woman is going to die from breast cancer before she’s 70 then these risks were drifting up during the ‘50s, ‘60s, ‘70s, ‘80s, they were just drifting gently up and then suddenly these treatments started to become available and it turns over and goes steeply down and it’s now less than half of what it was.

Now, a lot of those treatments would be available in the cities of middle income countries so you could have the simple breast cancer treatments available, the problem, of course, is people don’t turn up early enough and various other things but that’s an example.

Intestinal cancer is another example where actually there has been a succession of moderate gains and actually the national death rates are down quite substantially. If you look at the UK intestinal cancer death rates they’ve come down. Death rates are drifting down due to a lot of not very striking improvements in treatment. A lot of that could be spread at least to the cities of middle income countries.

Does early detection have a role?

Oh yes, it depends on the type of cancer of course. With cervix cancer when you’re screening for cervix cancer you’re not going for early detection, you’re going for detection of lesions before they are cancer at all so you’re actually preventing cancer arising by finding things that might turn into cancer and taking them out before they do. So that can work well where it’s practicable to organise it. But if you take worldwide, yes, a lot of the places with quite a lot of cervix cancer could get screening better organised. And there’s plenty of prospects that the use of HPV tests, testing for the causative virus, could improve the screening procedure and mean that unskilled staff could actually do the screening. The trouble is that it’s really quite complex to interpret slides down microscopes whereas tests for particular types of virus could be done by trained technicians who aren’t anything like as highly trained as the histologists.

What are your key clinical messages to help prevent cancer and lower cancer mortality?

For the general community the key thing is just don’t mix up big causes with small causes. Smoking is enormous, it’s something that those who smoke can do something about. We’re going to have hundreds of millions of tobacco deaths over the next few decades and if you are a smoker then stopping really works ridiculously well. If you can stop smoking before you’re 40 then you’ll avoid more than 90% of all the risk of tobacco killing you. If you can stop before 30 you will avoid more than 97%. Of course it’s better not to have started but that’s not much use if you already smoke. So if people smoke then stopping really works. I think that the WHO’s present concerns about nicotine delivery devices are misplaced. There’s a debate on this today and I think that they should be encouraged, yes it is an addictive drug, an addiction to nicotine is causing five million deaths a year, that’s ten times as many as the total number of deaths from malaria, because that’s what’s  making people smoke. But the nicotine delivery devices, if they’re not marketed in ways which cross-market, which cross-brand with cigarette smoking, really have quite a lot to offer. I think that we’re worrying so much about whether we can guarantee the safety of the nicotine delivery devices but certainly we can guarantee the danger of continuing to smoke. So I would say, yes, stop smoking. Most people stop smoking without any pharmacological help, if pharmacological help helps you then use it, just do take that seriously. More than half of all smokers get killed but stopping works, it’s your choice.

A lot of the other concerns are perhaps exaggerated and they can divert attention from the fact that one thing is bigger than everything else put together in those cases. Now obviously if you’re a woman living in some part of China where there is still a lot of aflatoxin contaminating stored foodstuffs then this is irrelevant. Most Chinese women don’t smoke and HPV vaccination is no use; you can vaccinate the kids but that’s not going to protect those who are already born, and you can reduce aflatoxin contamination. So IARC has got a nice handbook on reduction of aflatoxin contamination in poor countries and that really works. Where you’ve got enough aflatoxin to really be causing liver cancer you can reduce it just by changing the way the food is stored. So there are other things to do; there are workplace things – asbestos was the biggest occupational disaster there ever was; radiation protection has got to be continued. Do these various things but don’t let the small divert attention from the big. And don't minimise the importance of treatment. Where surgical services are available you would like health structures to be such that they can be offered. China has just got health insurance for the rural population so suddenly a woman in a village who has got a cancer that should be operated on, should be cured in her breast, but who would not previously have been able to do so unless the entire village clubbed together to pay for it, suddenly can go to hospital and at least she’s got the chance that’s offered by surgery. I think this will also have somewhat of a cultural effect that instead of knowing that cancer kills you and knowing that it’s better not to know about it, that one could get to the point where they would go and get things operated on. So treatment has a serious part to play. But in most countries, in most poor countries, the cancers turn up so late that they’re essentially inoperable.