Cervical cancer vaccine brings hope to patients

It was a test tube baby, born on a Thursday afternoon in April to two proud parents and some very high expectations.

How pretty it was, and oh, how tiny. Professor Ian Frazer, one of the men responsible for the new arrival, could only make it out through an electron microscope, magnified at least 50,000 times. The Scottish native can't remember the exact date when he first clapped eyes on it, but he remembers vividly what he saw: a perfect array of triangular faces staring back at him.

And so the beginning of a potential cure for two types of human papillomavirus (HPV), responsible for two thirds of cervical cancer cases, was born.

Frazer remembers making the announcement to his wife and children. For once, the then-junior doctor told his family, something at work - a cupboard-sized lab in the basement of Brisbane Hospital - had actually gone right.

Indeed it had. Last week, that pretty little something was hailed as "the biggest breakthrough in women's health since the contraceptive pill". Drug company Merck announced its first large study of the genetically engineered vaccine, called Gardasil, had proven to be an astounding 100 per cent effective against HPV. The extensive study involved almost 11,000 women in 13 countries.

Another drug company, GlaxoSmithKline, is not far behind with a similar vaccine showing similarly spectacular results. Both could be on the shelves as early as next year.

There is talk Frazer, who once had to re-mortgage his house to host a conference on his work and now stands to earn about $1 million a year in royalties from the vaccine, might receive a Nobel Prize for the discovery.

Though the signs look healthy, many issues still need working though. How does it work? Who should get it? How long will it last? Is it going to be expensive? And will this mean an end to those awful pap smears? "From our point of view, this is great news. We're enthusiastic about it," says Dr Peter Dady, medical director of the Cancer Society. "HPV does give rise to some rather nasty infections in the female genital tract ... so obviously if you vaccinate against it, that's a pretty damn important first step."

But he is also cautious. "It is important to realise that developments in medicine are made in small steps. Just occasionally a magic bullet comes through, but it's very rare."

Frazer himself is realistic. Its success will be most keenly felt in developing countries and those with poor or no screening programmes, where the death rate is four, even five times that of developed nations. The hardest issue, he thinks, is tackling how to get people, especially in these countries, to take the vaccine.

So Frazer will start with the easiest question: how the vaccine works.

"It's just basic immunology," he says understatedly. The discovery was, it transpires, unplanned. Frazer and his colleague Dr Jian Zhou were trying to find a treatment for women already infected with HPV. Because they preferred not to rely on patients as guinea pigs, they tried to mimic the lifecycle of the virus in a test tube. The first step was to make the coating of the virus, without all the nasty stuff inside, and that's what happened on that lucky Thursday.

"It was a bit of a serendipitous thing really. We weren't shooting for a vaccine of that sort, but when it came our way, we weren't going to let it go by."

They immediately realised that if their test tube baby looked like the virus to them, it might look like the virus to the body's immune system as well. By injecting the faux-virus into the muscle, the immune system is duped into panic mode, producing neutralising antibodies which mop up the faux-virus, and any real HPV that invades later in life.

"The immune system's got a very good memory for specific things. You can trick the body into thinking it's seen the problem, and it learns the trick for the rest of its life."

The way this fairly common but hard-to-detect virus invades is through sex. Therefore, to be most effective, the scientific boffins have concluded the vaccine should be given to children before they become sexually active. They say we could be talking as young as nine years old.

In America, the suggestion a child be lined up for a jab against a sexually-transmitted disease has caused a kerfuffle, with religious groups arguing it sends a message to kids that it's okay to have sex.

"Get real," is the response from Immunology Advisory Group head Dr Nikki Turner. "Yeah, it's an STD, but it's also cancer. This is not about condoning promiscuity, this is about treating a virus that can cause cancer. You only ever need one sexual partner who's had one sexual partner in their life to get this virus, and that's not an unreasonable assumption for any of us."

Turner, who favours immunisation at the age of 11, at the same time as rubella shots, does not believe New Zealanders will raise moral objections to the vaccine.

However, whether they will object to another mass immunisation programme is another question. The meningicoccal B campaign was the most recent to expose this public-health debate: is the Government playing mother to parents fearful only because of the Government's own scare tactics, or is it using its knowledge and ability to save lives?

Veteran women's health advocate Sandra Coney, perhaps best known for her role in the Cartwright Inquiry into botched cervical cancer experiments at National Women's Hospital in the 1980s, is one who is reluctant to support mass immunisation.

"Big government-led campaigns done for the good of the population can have really awful effects," she says. "Things like consent and information are extremely important. The responsibility absolutely lies with the people who go out and push these things."

But for Dr Ai Ling Tan, who is part of the fantastic team at Auckland's Greenlane Hospital who deals with patients fighting cervical cancer every day, immunisation is at least worth considering.

Tan, who is often the one who has to tell someone they have cervical cancer and face radical hysterectomy, chemotherapy, or both, would not begrudge a medical miracle doing her out of a job.

"If you could prevent it, of course that's better. There's nothing worse than having to tell a woman, regardless of her age, that she's got cancer. It's devastating to tell someone who hasn't had a family she won't be able to have children. You don't want to put any woman through that."

But cancer, in all its evil shapes and sizes, will keep her busy for a bit longer yet, she fears.

Tan and the team also see the benefits of the government-led mass screening effort. Every week about 60 women wait in the newly-renovated reception area. They're either here for a colposcopy - a pre-invasive, pre-cancerous treatment when a woman has had an abnormal pap smear - or a follow-up. Some are nervous. Tan is the first to acknowledge a colposcopy is not an experience women tend to cherish. But nor it is as painful as it sounds, she adds.

Indeed, despite its abysmal first run, the national cervical screening programme seems to be working well. Ministry of Health figures show that since 1991, when it was established, it has reduced cervical cancer incidence by about 40 per cent and mortality by up to 60 per cent.

Frazer: "For all the problems there may have been in New Zealand, it's still a much better programme than exists in many parts of the world where there are supposed to be good schemes."

There are, of course, a host of other issues attached to the efficacy of immunisation. Half of the 180 cases in New Zealand each year are found in women who have not had a smear test. It is likely that these are the same people who will fall through the cracks of an immunisation programme.

One doctor worries about the possibility a fix-it jab will make women think, incorrectly, that they no longer need to have regular pap smears. Another raises questions about whether, further down the track, the virus might mutate and fight back.

But, says Dr Hazel Lewis, clinical director of the screening programme, every new development has its bad points and its detractors. Yes, cervical cancer is quite rare and the vaccine does not stop about 30 per cent of its causes and it is fundamental women still get smears. But she's still excited about the breakthrough and the changes it could bring about.

"There are studies in the US and other countries that have shown there is quite a bit of acceptance around the vaccination. Give women some credit. Women are the same all over, whatever their culture. They care about their health."

Lewis says what is now needed is a treatment for women already infected with HPV. Making impressive headway into just that is our own Dr Merilyn Hibma, who heads of a four-strong research team at Otago University's microbiology and immunology department.

The virus is very good at "hiding" itself in the body, says Hibma, so the immune system doesn't realise it should be mounting an attack until too late. Hibma is currently looking at ways to expose this sinister cloaking mechanism.

Success is a way off, says Hibma, but Frazer's success has given all researchers a boost - and served a reminder that funding for health and science research does pay off.

Should the anti-HPV vaccine hit the shelves and our schools in the next few years, it won't mean the end of screening by any means. But couple immunisation with screening and patience, and you'll get a formidable combination, says Lewis.

"Maybe in 10 or 20 years' time we will start to see the change. It may mean screening is required less frequently, or later in life. It is a huge breakthrough. In 20, 30 or 40 years, we may see no more of what is a nasty disease, which is something we all hope for."

Ultimately, whether immunisation is added to the arsenal against cervical cancer will come down to how effective the drug is, how much it is needed, and the dreaded cost/benefit analysis.

Back in Brisbane, Frazer acknowledges that with health dollars limited, how - or even if - this vaccine is implemented depends on its cost. He doesn't yet know how much the drug companies will charge.

The meningicoccal programme has so far cost about $200 million. But even then, argues Frazer, there's a social utility to a vaccine to prevent cancer which can't be measured in terms of dollars.

But like a concerned father, he is pragmatic about the future of his brainchild. Though he stands to be a very rich man if the vaccine is marketed, he still rides his bike to work, and after the media circus of the past week, he is keen to get back to what he does best.

He is now tackling influenza - another epidemic will come, he says, and we need to be better prepared. And after that?

"Most people, if asked, would like to live long, healthy lives, and that's a pretty good thing to shoot for."

- HERALD ON SUNDAY