Researchers have discovered how a virus found in both humans and cows that causes cervical cancer in women disguises itself to hide from the immune system.
Certain types of human papillomaviruses (HPV) cause cervical and vulval cancer. However they are difficult to treat because following initial infection the virus can lurk in cells undetected for years before becoming active.
The research, funded by Cancer Research UK and the Medical Research Council, is published today1 and could lead to a new treatment for the disease in its earliest stages.
The researchers discovered the virus’s method of masquerade in the bovine papillomavirus (BPV), but the mechanism is shared by the virus that infects humans.
The team, led by Professor Saveria Campo at the Institute of Comparative Medicine, Glasgow University, has discovered that a papillomavirus protein called E5 makes the virus a master of disguise. This deception prevents the body’s natural defences from spotting the infection early and dealing with it.
There are over 70 types of HPV but only some are linked to cervical and vulval cancer. These high risk types can cause changes in the cells covering the cervix or vulva that make them more likely to become cancerous.
“We know the viral E5 protein is present in high risk types of HPV. Now we understand how it works it could lead to treatments that will target this protein and inhibit it. The body will then make an effective immune response – stopping infection early and preventing the development of cancer,” says Prof Campo.
E5 works by blocking the transport of a molecule called MHC class 1 to a cell’s surface. This molecule would normally act as an alarm signal to the body’s immune system – warning that the cell was infected and needed to be attacked.
Cancer Research UK experts have reported that around 99 per cent of cervical cancer biopsies contain high risk HPVs. The virus is also believed to be responsible for between 30- 50 per cent of vulval cancers.
Dr Lesley Walker, Director of Science Information at Cancer Research UK, says: “Particularly with cervical cancer we’ve seen a huge drop of 33 per cent in the number of cases since 1982, largely due to screening.
“An effective HPV treatment that allows the immune system to do its job could really push these figures down further. By preventing women developing the earliest stages of infection we can block the route of the cancer’s development.”
About 3,200 women are diagnosed with cervical cancer each year in the UK. It is the second commonest cancer in women under 35.
Sir Paul Nurse, Chief Executive of Cancer Research UK, says: “The cervical screening programme has been highly successful. The prevention of cancer at as earlier point as possible is of great importance – Prof Campo’s study of the masking mechanism is another step towards achieving this goal for cervical cancer.”
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- Oncogene21 (51) pp.7808-7816
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The human papilloma viruses (HPVs) are a group of more than 70 different types of virus. They are given numbers to distinguish them. Some types of HPV are linked to cervical cancer, primarily numbers 16 and 18.
The research was conducted on bovine papillomavirus. Both this virus and a cancer causing virus, HPV type 16, use E5 to inhibit MHC class 1. E5 works by trapping MHC class 1 in the cell’s Golgi apparatus – the cell’s transport centre.
HPV is sometimes called the wart virus or genital wart virus as some types of HPV cause genital warts. In fact, the types of this virus that cause warts are not the types that cause cervical cancer.
There is currently an NHS pilot screening programme for HPVs.
Professor Campo is part of a MRC cooperative group specialising in virology and “viruses of medical importance” based in Glasgow. This group shares knowledge, equipment and techniques about molecular mechanisms used by different viruses.
