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Vaccines to Prevent and Treat Cancer

Vaccines to Prevent and Treat Cancer

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Virus infections are responsible for about one in five human cancers. In his lecture Professor Frazer discussed how this knowledge has been used to develop vaccines for the prevention of cervical cancer, and how they have been shown to be effective. The challenge is to see them used in the developing world, where the majority of cervical cancers occur.

This lecture was in association with the Scottish Cancer Foundation, supported by The Cruden Foundation.
Virus infections are responsible for about one in five human cancers. In his lecture Professor Frazer discussed how this knowledge has been used to develop vaccines for the prevention of cervical cancer, and how they have been shown to be effective. The challenge is to see them used in the developing world, where the majority of cervical cancers occur.

This lecture was in association with the Scottish Cancer Foundation, supported by The Cruden Foundation.

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Published by: The Royal Society of Edinburgh on Aug 23, 2013
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The Royal Society of EdinburghJoint lecture with the Scottish Cancer Foundation,supported by the Cruden Foundation
Vaccines to Prevent and Treat Cancer 
Professor Ian Frazer FRSCEO and Director of Research,Translational Research Institute, Brisbane, Australia
24 June 2013Report by Jennifer Trueland
Sometimes described as ‘God’s gift to women’ for his work in developing the HPVvaccine which aims to wipe out cervical cancer, Professor Ian Frazer gave somefascinating insights into the role that immunotherapy already plays in preventing andtreating cancers – as well as some glimpses to the future.
If he’d been asked to give this talk 20 or 30 years ago, said Professor Frazer, itwould have been a very short lecture indeed; it’s only recently that we’ve known forsure that viruses cause cancer in humans. Likewise, using the immune system toprevent or treat cancer is a relatively new concept, but one in which there has beentremendous progress in the last two to three decades.In his lecture, Glasgow-born and Edinburgh-educated Professor Frazer outlined the21
st
Century challenge of healthy ageing, explained why cancer is such an importanttarget, and looked at what can be done to prevent and treat it. He focused inparticular on the human papilloma virus (HPV), which causes cervical cancer, and onthe vaccine (which he was instrumental in developing) that is already drasticallyreducing incidence of the disease in countries running immunisation programmes.Finally, he looked at the prospects for using immunotherapy to treat established HPVinfection, and the challenges that remain.So why should we focus on cancer? In Australia, cancer is the most common causeof death, and there have been estimates that this will be the case worldwide by 2050.Around 70 per cent of cancer is preventable (with effort) and we can now curearound 50 per cent. Our chances of getting cancer depend on our genes (accountingfor around 10 per cent of risk); what we do to ourselves, for example, smoking (30per cent); what we do to the environment (30 per cent); and what we catch it from (30per cent). There’s quite a listof things we can do to prevent cancer, he said, but themessages have tended to be confusing, and too full of ‘thou shalt nots’. For example,on one page of a newspaper it might say that coffee prevents cancer, while anotherpage might say it causes it. “It’s not just about telling people what they need to do,”he added, although he pointed out that behaviour modification is effective. Forexample, smoking accounts for around 40 per cent of avoidable cancer worldwide,obesity (in the developed world) around 10 per cent, and alcohol also around 10 percent. If these avoidable cancers were prevented, then it would save around 30 percent of healthcare costs – and mean more money was available for medicalresearch, and for treating the cases that remained.Immunotherapy, that is, using the immune system to tackle disease, is now anestablished component of cancer therapy. There are several approaches. These
 
include prophylactic vaccines, for example, hepatitis B and HPV, and usingimmunotherapy to treat cancers in practice, for example, Herceptin for breast cancer.Around 20 per cent of cancers are caused by infections, including papillomavirus,hepatitis B and C, and Epstein Barr virus. Focusing in particular on cervical cancer,he pointed out that it is a disease of the developing world.Over the years, there have been a number of theories about what causes cervicalcancer; perhaps most notably (following a study comparing incidence among nuns tothat among non-nuns, which found abnormal cells in the latter but not the former)that it is not caused by ‘licentious behaviour’ but that the risk is greater amongwomen who are ‘excessively sensitive morally’. It is now established, however, thatcervical cancer is a rare consequence of chronic infection with papilloma viruses,which are transmitted sexually. Since it is a challenge to control infection, it is betterto prevent it – hence the search for a vaccine.[At this point Professor Frazer declared a potential conflict of interest, in that he andthe University of Queensland benefit financially from the commercial sale of theprophylactic HPV vaccines discussed in the talk.]It was around 1980 that Harald zur Hausen found the viral link between HPV andcancer; he was disbelieved at first, but went on to win a Nobel Prize. HPV infection iscommon, and 95 per cent will resolve spontaneously, but around two per cent willprogress to cancer over 15 years. Unusually, it is possible to detect pre-cancerouscells one to two years after infection – it is these cells which are detected viascreening programmes, when treatment will be effective in most cases.It took around 15 years to develop an HPV vaccine, in what Professor Frazerdescribed as a billion-dollar process. Development of the vaccine was possiblebecause of genetic engineering research, and was challenging in as much as itnecessarily had to involve many thousands of people and a ‘hard end point’ to proveefficacy, and even more to prove safety. Post-marketing surveillance has shown thatfrom 44,000,000 doses over 24 months, 12,424 people reported possibly associatedevents, mostly non-serious, with fainting the most common. Adverse events inpregnancy were similar in both the vaccine and the placebo groups.Following the introduction – and good uptake – of the vaccine in Australia, theproportion of Australian-born women with genital warts fell markedly (in younger agegroups). The proportion of heterosexual men diagnosed with genital warts also fell(across all age groups) suggesting that vaccinating women protects men (who werenot vaccinated) too.Professor Frazer described a project to introduce an immunisation programme inVanuatu, a group of islands off Australia with just five doctors for 250,000 people,one vaccine fridge, no reliable electricity, and high risk of HPV infection andassociated pre-cancer. Immunisation was delivered as part of a programme whichincluded educational sessions, aimed at parents, children, school staff andgovernment. The people of Vanuatu were keen to protect their women, and uptakerates were high. “Mothers tell their children: ‘get this shot’,” he said.Bhutan, a poor country which values its health, did it too, largely down to influencefrom the ‘royal grandmother’, he added. Professor Frazer said the case forintroducing immunisation programmes worldwide is compelling, adding that theevidence suggested it has a bigger impact in terms of benefit than the polio vaccine.But what about when the virus is already there? Professor Frazer said there is noevidence that cervical cancer vaccines are therapeutic for existing HPV vaccines.Despite promising results in the lab, it has to be borne in mind that “mice lie”, he

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