CSL celebrates cervical cancer vaccine success

Cancer research is all hard slog, a long journey of many small steps, punctuated all too rarely by a genuine leap forward -- like the one announced today by CSL and its partner, pharma giant Merck and Co.

It won't get much better, or simpler: a prototype vaccine that completely protects women against the most dangerous strain of Human Papilloma Virus (HPV), the agent of genital warts and cervical cancer, the second most common female cancer.

"In my medical research career, working on women's health, I'd put this as number 1," said Prof Suzanne Garland, of the Royal Women's Hospital in Melbourne. "We have a virus that has been shown to be oncogenic, which has been listed by the World Health Organisation as a cancer-causing agent, and we are now trialling a vaccine, with fantastic preliminary data. It's phenomenal news."

Garland described the technology behind the vaccine as "potentially one of Australia's most important medical discoveries."

Merck's proof-of-principle study, published in this week's issue of the New England Journal of Medicine, confirmed the efficacy of a monovalent vaccine, which targets only strain 16, the culprit in around some 50 per cent of cervical cancers.

Garland's team is already trialling the new commercial prototype of the Merck-CSL Human Papilloma Virus vaccine -- a polyvalent vaccine developed to protect against the four major pathogenic strains of the virus.

Melbourne's Royal Women's Hospital is currently attempting to recruit 300 healthy young women aged between 16 and 22, who have no history of genital warts or a positive pap-smear test, in the Australian leg of an international trial of the polyvalent vaccine.

It covers four HPV strains: 16 and 18, which account for 70 per cent of cervical dysplasia and cervical cancer, and strains 6 and 11, which cause 90 per cent of genital warts cases.

The multi-centre trial of the polyvalent HPV vaccine will run for four years, and Garland, like CSL's director of research and development, Dr Andrew Cuthbertson, believes the vaccine could be available in around five years.

It has already been more than a decade in development. In 1991, Professor Ian Frazer, of the University of Queensland, identified the virus' L-1 coat protein of HPV as a prospective target for a vaccine.

The L-1 protein shows considerable variation between HPV strains, so a successful vaccine would have to generate a neutralising antibody response against the major pathogenic strains that cause genital warts and cervical cancer.

CSL signed an agreement with the University of Queensland in 1991 to commercialise Frazer's discovery -- the vaccine uses recombinant DNA technology to produce L-1 proteins that aggregate into f virus-like particles.

The particles, lacking the virus' genetic material, are non-infectious, but generate a strong neutralising antibody response.

In 1995, CSL gave Merck an exclusive licence to commercialise the technology, in return for a royalty on all overseas sales, and the right to market the vaccine itself in Australia and New Zealand.

"We know that about 20 per cent of women will be infected by HPV-16 at some time in their lives," Cuthbertson said. "In most, the infection resolves spontaneously, but a small number of women will develop cervical dysplasia, which, if undetected, can develop into cervical cancer. In Australia, about 1000 women per year develop cervical cancer, despite our excellent screening programs."

Cuthbertson said the vaccine represents "the best face of academic-industry collaboration in Australia".

"Ian Frazer and CSL have delivered the basic advance, and we were able to attract Merck as a partner," he said. "We stated in 1991 that development of a vaccine would require dedication and patience -- we now have a vaccine, and we believe it represents a fabulous achievement for Australian science."

In a commentary accompanying the paper in this week's New England Journal of Medicine, Prof Christopher Crum from the Harvard Medical School said: "This study puts to rest the recurring question posed by immunologists as to whether this type of vaccine can protect the highly vulnerable cervical epithelium (lining) from cancer-causing HPV.

"The study demonstrates that the vaccine not only prevents the disease from developing, but also prevents the causative agent from residing in the genital tract."

Garland said that if the polyvalent vaccine proved as successful as the monovalent prototype, it would be used to vaccinate adolescent girls -- and boys -- before they became sexually active and were exposed to HPV.

Garland said it would be necessary to vaccinate both sexes, because infected males play a significant role in transmitting the virus to females, and are also susceptible to genital warts.

• The Royal Women's Hospital has established a web site to recruit young women for the vaccine trial. Potential volunteers can also call 1800 55 88 66.