Every year more than 530,000 women worldwide receive the diagnosis of cervical cancer. It the second most common type of cancer in women, and one of the deadliest (about 275,000 women died from cervical cancer in 2013 alone, according to the World Health Organization). But there is hope: Australian immunologist Ian Frazer and his late Chinese colleague Jian Zhou, who died in 1999, developed a vaccine against cervical cancer. The method is ground-breaking because it focuses on prevention, which can be life-saving, in particular for women without regular access to healthcare.
Developing a vaccine has saved countless lives and also saved many women from a protracted and painful course of treatment, involving surgery and chemotherapy.
|Head Researcher||Professor Ian Frazer|
Prof Jian Zhou
|Body Part||Cervix Uterus|
Scottish-born Ian Frazer based his ground-breaking invention on the research of the German physician and Nobel Prize Winner Harald zur Hausen. For a long time, the medical world believed the herpes virus caused cervical cancer. In 1976, it caused a sensation when Dr zur Hausen first mentioned the human papillomavirus (HPV) as playing a role in cervical cancer. The sexually-transmitted virus infects the skin and mucosal tissues, which in the worst case can cause cervical cancer. In the early 1980s, the German virologist then identified the so- called “high-risk” types of HPV, mainly HPV 16 and HPV 18, as the main cause behind more than 70 percent of all cervical cancers, as well as a number of other types of cancer in both women and men.
Ian Frazer put these findings at the centre of his own research. As early as 1985, having emigrated to Australia, he set up the world's first research group to concentrate solely on developing a vaccine against cervical cancer. However, it proved impossible to grow the HPV virus in the laboratory, making a vaccine based on live viral elements unfeasible.
After many years of experimenting and various setbacks, Ian Frazer, together with virologist Jian Zhou, whom he had met whie on sabbatical in Cambridge, cloned HPV surface proteins for expression in vaccinia virus, and determined a way to enable these proteins to self assemble into virus like particles, representing the empty shell of the virus. The human immune system reacts to these harmless virus- like particles and forms antibodies, thereby building immunity. The vaccine derived from this offers full protection from the dangerous HPV types 16 and 18.
From these first successes, it took almost 15 years until the vaccine was ready for market. In 1991, working at the University of Queensland, Frazer and Zhou filed a patent application describing the necessary steps to enable self assembly of the viral capsid proteins in vitro using eukaryotic cells, and an appropriate transcription start site for the L1 capsid open reading frame. This was a milestone for production of the now-widely available HPV vaccines. In 1995, Frazer and Zhou licenced the technology through CSL to US pharmaceutical company Merck & Co, who used it to develop a vaccine based on virus types 6,11,16 and 18, now sold as Gardasil. After three years of testing, the scientists completed the first trials on humans in 1998 with outstanding results. A cycle of three injections offers full protection against HPV for up to five years. After Jian Zhou’s unexpected death in 1999 due to an illness at the age of 42, Ian Frazer continued their joint work until the vaccine was ready for market.
In 2011, Professor Frazer became the founding CEO and Director of Research at Australia’s Translational Research Institute (TRI) in Brisbane where today he researches therapeutic vaccines for patients already infected with HPV. The vaccines are currently in clinical testing. In 2014 he returned to research at the University of Queensland , but remains an Ambassador for TRI and Chair of the TRI Foundation.
In 2006, Gardasil was approved by the US Food and Drug Administration (FDA). The vaccine is now used in 121 countries and has been administered more than 125 million times. In 2013, Gardasil reached total worldwide sales of about EUR 1.49 billion.
In December 2014, the FDA approved Gardasil’s follow-up vaccine which is designed to protect against nine different strains of HPV and sales are expected to reach about EUR 1.55 billion by 2018. This vaccine received preliminary approval in Europe at the end of March 2015.
UK pharmaceutical company GlaxoSmithKline produces another widely-used cervical cancer vaccine, Cervarix, also based on Frazer’s and Zhou’s technology .
The WHO as well as public health agencies in Australia, Canada, Europe and the United States now recommend vaccination against HPV for young women aged 9 to 25. Most countries in the developed world now have government-funded school or community-based public health programs targeting 12-14 year old girls. Australia also has a public health program for boys, as HPV also causes some cancers in men.
In the western world, cervical cancer can be treated if diagnosed in good time, and, as a consequence, few women die from it. According to the WHO about 85 percent of all deaths from cervical cancer occur in low or middle-income countries. Without any interventions, the number of cervical cancer deaths will rise to over 400,000 by 2035, virtually all in the poorest countries.
The vaccine signifies a vital step forward in the fight against cancer, in particular for regions without basic healthcare and no preventive diagnostic procedures. Professor Frazer has been working on programs to help prevent cervical cancer in Vanuatu for around five years as there is a huge burden of disease among younger women. One in a hundred healthy women walking the streets already has cervical cancer, and, because there is no treatment available, the cancer will eventually progress and kill them. So this is a disease that occurs in twenty year olds in Vanuatu and really the only hope for preventing cervical cancer in Vanuatu is a universal vaccination program.
The University of Queensland has therefore waived royalties on Gardasil sales in 72 developing countries.
There have been a number of research trials and studies, in Australia and in other countries such as the United Kingdom, where there are government-funded, school-based vaccination programs, to determine whether Gardasil and Cervarix, another vaccine based on Prof Frazer’s work, reduce genital warts which can lead to cervical cancers.
Since the National HPV Vaccination Program was made available to females in Australia in 2007, studies have shown a greater than 70% uptake of the vaccine and a dramatic drop in HPV-related infections in females eligible for vaccination, along with declines in genital warts diagnoses in females, and in males due to herd immunity. As well as providing males with comprehensive protection against a range of HPV-related cancers and disease, vaccinating males will help to protect the almost 30 per cent of Australian females who remain unvaccinated.
Professor Ian Frazer