The HIV virus
Cancer and AIDS – two of the most powerful and emotive words in the English language, and two diseases that touch the lives of millions of people across the world. Many researchers dedicate their lives to studying them.Cancer Research UK is working tirelessly towards beating cancer. And thanks to our pioneering work, countless lives have already been saved.
Of course, as no doubt anybody reading this is aware, we’re not an AIDS charity. But in this post – the fourth in Our Milestones series – we’re stepping back in time to the 1980s, when one of our scientists helped solve a complex medical mystery with implications for both AIDS and cancer.
Background: the early 1980s
It’s hard to believe – given the devastating global impact of the disease – that ‘AIDS’ only entered our vocabulary in the 1980s. It was early in that decade that US health officials in New York and California began to see an unusual number of young men appearing in clinics with small, purplish skin marks, or lesions, on their bodies.
It turned out that the lesions were not a new phenomenon. In fact, as far back as 1872 a skin expert at the University of Vienna called Moritz Kaposi spotted these same marks in a group of his patients.
Kaposi recognised that the lesions were actually a type of cancer – the purplish colour was from the tumour’s blood vessels leaking into the surrounding tissue. A couple decades later this cancer became known as Kaposi’s sarcoma, or KS for short.
The US doctors soon realised that they were witnessing an unprecedented rise in people with KS, but they were flummoxed as to why. The only clue was that all the young men who were being diagnosed with KS at this stage were homosexual.
Intriguingly, KS was also known to affect people who had undergone organ transplants. These people take drugs to suppress their immune system, to prevent rejection of the transplant. This link between KS and a weakened immune system was another vital clue.
Of course we now know that KS – and certain infections – are a sign of what we now call ‘Acquired Immune Deficiency Syndrome’, or AIDS, caused by infection with the human immunodeficiency virus (HIV).
It also quickly became apparent that AIDS affects both men and women and that HIV can be transmitted in a several ways, such as through unprotected sex, through injecting drugs with infected needles, and through blood transfusions.
So it is curious but true that a cancer was a harbinger of the AIDS epidemic – the outbreak of Kaposi’s sarcoma was how we first learned that AIDS existed.
So where does our Cancer Research UK scientist come into the picture? The answer comes a little later in the decade. Even after AIDS was accurately described and its cause – HIV – was discovered, there were still some unanswered questions. Why was KS one of the first ‘signals’ of AIDS? Was it caused by HIV itself or was it caused by something else? What might this ‘something else’ be?
This question intrigued Professor Valerie Beral, a world-leading epidemiologist (an expert in studying the patterns of disease within populations). In 1988, Professor Beral was offered the position of Director of our Cancer Epidemiology Unit in Oxford. But before moving to Oxford, she spent 12 months as a ‘visiting scientist’ with the Centres for Disease Control in Atlanta, Georgia, in the United States.
Given her role with Cancer Research UK, she was keen to study KS in people with AIDS.
What did they do and what did they find?
By 1990 Professor Beral was working back in the UK and had published the results of her US research with her colleagues Thomas Peterson, Ruth Berkelman and Harold Jaffe. The work appeared in The Lancet and was entitled “Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection?”
As the title suggests, the scientists built a compelling case for KS being caused by a sexually transmitted infection in people with AIDS – but not by HIV.
To come to this conclusion, they analysed 8 years’ worth of information about more than 90,000 people with AIDS. The CDC had been collecting data about everyone diagnosed with the disease in the US since 1981 – information like gender, age and country of birth.
Crucially, the CDC also classified people into different ‘transmission groups’, such as whether they were homosexual, bisexual or heterosexual; whether they had received a blood transfusion; and whether they were an injecting drug user.
Professor Beral and her colleagues drilled into the data and found that KS was exceptionally common in people with AIDS. In fact, it was at least 20,000 times more common than in the general population.
More intriguing still, there was a huge variation in how common KS was in different groups of AIDS patients, depending on how a person got the HIV virus. The big finding was that KS was more common if a person had contracted HIV through sexual contact than by any other way, like through a blood transfusion.
The risk was greatest in homosexual and bisexual men. In fact, 20 of every 100 homosexual men with AIDS developed KS, whereas 3 in every 100 people who’d contracted HIV through a blood transfusion had KS. This difference was much greater than would be expected by chance.
A new perspective
Although they were not the first to suspect that KS might be caused by an infection separate to HIV, Beral and her colleagues were the first to provide any concrete evidence to back up this theory.
They combined their analysis of the numbers with some compelling arguments:
- If KS was simply a ‘symptom’ of AIDS, then you would expect that whichever way a person contracted the HIV virus – through non-protected sex or other means – the number of individuals developing KS would be about the same in each group. This was clearly not the case.
- Other groups of people with suppressed immune systems, such as transplant recipients, are also at risk of KS. This points the finger to HIV infection causing the right ‘conditions’ for KS to develop – immune suppression – rather than actually causing it.
- Very few agents are known to increase the risk of cancer even by 100 times, let alone 20,000 times. And one of the most well-known examples of the time was infection by hepatitis B virus causing some liver cancers. This strengthened the case for KS being caused by an infection.
What’s the impact of this work?
Understanding what caused KS in AIDS patients was one of the hot topics of the late 1980s and early 1990s, and this was an influential piece of research.
Following the publication of this work, scientists began experiments to track down the infectious agent that Prof Beral’s research alluded to. And in 1994, a team of researchers in New York discovered a virus called ‘HHV-8’, which was found to cause KS.
So this work led to the unravelling of a medical mystery, illuminating how the outbreak of KS occurred in homosexual men. And it also paved the way for a whole raft of investigation by other Cancer Research UK scientists.
For example, further work by our researchers in the 1990s was crucial in showing how HHV-8 infection leads to cancer. And we’re currently funding the research of Professor David Selwood, who’s working on developing treatments for KS.
Our scientists’ work is tremendously diverse, but united by our shared aim of beating cancer. Since the publication of this paper, Professor Beral continued to work on KS, and now works on The Million Women Study, which is helping us understand how a woman’s lifestyle can influence her health and chances of developing breast cancer.
And we’re delighted that Professor Beral was named on this year’s New Year’s Honours list, and has been awarded a DBE for services to science – it’s a well-deserved honour.
- BERAL, V. et al (1990). Kaposi’s sarcoma among persons with AIDS: a sexually transmitted infection? The Lancet, 335 (8682), 123-128 DOI: 10.1016/0140-6736(90)90001-L