Battling the Big C
Bangkok Post, December 11, 2012

http://www.bangkokpost.com/news/health/325517/battling-the-big-c

The man who won a Nobel Prize for striking a blow against cervical cancer talks about the need to make the HPV vaccine more affordable and widely available and reflects on our ongoing battle with cancer in general.

When Prof Harald zur Hausen published an academic paper in 1972 suggesting that the human papilloma virus (HPV) played an important role in the genesis of cervical cancer, it received a chilly reception in medical circles. His findings also attracted a great deal of criticism from those scientists who believed that the herpes simplex virus was the cause of this cruel and often fatal carcinoma.

But the German virologist stuck to his guns. Back in the mid-1960s he had participated in a study in the United States into a virus called Epstein-Barr which was known to induce changes in human chromosomes.

Later he had been able to show that this organism had the ability to transform healthy cells called lymphocytes into tumorous growths, confirming that viruses can indeed cause cancer in humans.

Much later, in the early 1980s, the professor was working at the University of Erlangen-Nuernberg in the German state of Bavaria when he solidified the link between HPV and cervical cancer.

Not only were the conclusions of his ground-breaking paper subsequently confirmed, but he went on to identify several other strains of HPV that can cause disease in humans.

"After we isolated the high-risk papilloma viruses, the situation changed, of course, because everyone in the world could repeat our experiments.

"We also provided samples. It was easy to prove," said Prof zur Hausen who was in Bangkok recently to give the keynote speech ("Cancer prevention as a challenge for global health") during the 4th Asean "Bridges: Dialogues Towards a Culture of Peace" event.

Prof zur Hausen and his team identified HPV16 and HPV18, two strains of the virus which together are thought to be responsible for 75% of all cervical cancer, in 1983 and 1984, respectively. This breakthrough made it possible to develop a vaccine effective against four different types of HPV and this was first made available to the public in 2006.

In addition to HPV16 and HPV18, the vaccine also protects against two other strains which cause genital warts: HPV6 and HPV11. To provide the greatest protection, however, the vaccine should be given to people _ men as well as women _ before they are exposed to any of these four strains of HPV, the ideal recipient being someone who has not yet become sexually active.

With nearly 530,000 women worldwide being diagnosed with cervical cancer annually, according to World Health Organisation figures, and an average of 275,000 fatalities from the disease every year, the vast majority in developing countries, where it is the most common cancer in women, it is hardly surprising that Prof zur Hausen's discovery was universally acclaimed.

In 2008 the importance of his achievement was recognised when he was awarded the Nobel Prize for Medicine.
During his recent visit to Bangkok Prof zur Hausen voiced concern about the fact that developing countries, including Thailand, have only had limited access to the HPV vaccine.

"The price is the problem," said the virologist who is now 76 and officially retired from academic life. "It needs to be reduced."

Competition in vaccine production is a key factor in bringing the price down, he went on, pointing out that two pharmaceutical firms currently dominate the global market for this potentially life-saving formula.

"It's all about negotiations between governments and the companies. Some countries have been quite successful in doing this. Developing a national vaccination programme that is supported by the respective government would also be an important step," he said.

"Statistics can really demonstrate its [the vaccine's] effectiveness. I anticipate that if a global vaccination programme for hepatitis B and cervical cancer is set up, the rate of cancer in females would go down by 12 to 15% and in males by 4 to 5% because males are less susceptible to cancer formation by papilloma viruses."

The professor insists that men could also benefit from the HPV vaccine.

Although males seem to be less susceptible than women to HPV-related carcinoma, they also tend to expose themselves to greater risk, he pointed out, with men between the ages of 15 and 25 usually having many more sexual partners than women in the same age group.

''It's a message which really needs to penetrate to the population, to physicians, medical officials, health ministries and sons,'' he said.

Generally, it can take as much as 15 to 20 years after a person is exposed to HPV for cancer to develop. According to the professor, the vaccine may provide more than 90% protection from infection by HPV16 and HPV18.

In Europe and the United States, a startling 80% of women are thought to come into contact with one or other of these dangerous strains of the virus at some stage in their lives.

''It's probably protective against three other types that are closely related to 16 and 18,'' he said.

''These are types 31, 33 and 45. But there are a few [other] types that are not affected by the vaccination.''

Vaccination could also reduce the need for cone biopsies, he added. A cone-shaped wedge of tissue is removed from a woman's cervix and examined under a microscope, usually after a pap smear or colposcopy has indicated moderate to severe cell changes.

The procedure is carried out to confirm or rule out a preliminary diagnosis of cervical cancer or to see how extensive the disease is or to remove abnormal tissue as part of treatment. Since it is a very intrusive operation, it can increase the risk of premature birth or miscarriage in young mothers.

''Vaccination prevents the occurrence of [cancerous] lesions and that [obviates the need for] surgical intervention to remove these lesions. So it can make a big difference.''

The professor conceded that public anxiety over possible side-effects was understandable, given that the HPV vaccine was still relatively new, but he was quick to point out that since the vaccine does not contain any genetic material, there is no risk of it causing any long-lasting disease.

The only adverse effects reported have been attributed to allergic reactions, he said, and even those only occur about once in 100,000 cases.

The vast majority of press reports about the vaccine's side-effects are simply wrong, he declared.

''And [the incidence of side-effects is] extremely low even compared to some vaccines that are presently applied to small children. It's a safe and effective vaccine.''

He went on to cite a study carried out in Australia which found that side-effects were reported by only 25 of the 300,000 young girls who received the vaccine over a period of 1.7 years.

And when these 25 cases were carefully investigated, only three individuals were found to have had a genuine adverse reaction to the vaccine; the rest were judged to have merely had an allergic reaction to a protein in the vaccine.

''You need to balance this with the benefits of the vaccine. You can roughly calculate how many women are being protected against cancer, if, say, 100,000 girls are vaccinated, and how many of that same number, if not vaccinated, will die later on. And then you can calculate that the risk of developing allergies is one in 100,000 cases.

''I would greatly encourage girls to get vaccinated, just like my granddaughter was,'' he said. His interest in infectious diseases and microbiology began when he was a student doctor in the 1950s. In 1961, not long after graduating with a degree in medicine from the University of Dusseldorf, Dr zur Hausen got his first job at the Institute of Microbiology, also in Dusseldorf.

He later became convinced that viruses play a vital role in the development of many cancers. He noted that statistics indicate that more than 20% of global cancer incidence could be linked to viral infections.

''I feel that there are too many questions that need to be resolved,'' he said.

''Should I identify those agents? There are novel means and modes to prevent the diseases of hepatitis B and cervical cancer.

''We have a novel tool for the early diagnosis of a patient's risk and we have the means to interfere with agents present in those materials. But in order to be really successful in reducing the occurrence of cancer, we need to put more work into the preventive aspects.

''More needs to be done,'' said the Nobel laureate, whose list of international accolades also includes the Prince Mahidol Award.

So does he think there's a possibility that connections will be found between other viruses and other types of cancer?

''I guess there's a good chance. In epidemiological studies, there are certain types of cancers that might be linked to infections. We have been working on childhood leukaemia and there is some evidence that infection may play a role.''


The Asean ''Bridges'' series is facilitated by the International Peace Foundation. To find out more about upcoming events in the series (all free of charge to the general public) involving the Nobel laureates for Peace, Physics, Chemistry, Medicine and Economics as well as UN Special Envoy Romano Prodi (a former president of the European Commission), visit www.peace-foundation.net.