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Cervical cancer virus has longer reach

Published May 3, 2000

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Washington - The virus that causes most of the world's cervical cancer also appears to cause some oral cancer, mostly tumours found in the tonsils, scientists have reported.

The good news: tumours linked to the human papillomavirus may be much less deadly than other cancers of the head and neck that are caused by the usual culprits - smoking or alcohol.

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"We were surprised," said Maura Gillison, a Johns Hopkins University oncologist who began the study expecting to disprove the viral link. Instead, she said on Tuesday that "we think we found a cause for these cancers in people who don't smoke or drink".

Her findings are so strong that Hopkins researchers developing an experimental vaccine-like treatment to fight cervical cancer are now preparing to test the therapy on some oral cancer patients.

The discovery, reported in the Journal of the National Cancer Institute, was "very exciting", said Harvard medical school biochemist Karl Munger, an expert on human papillomavirus, or HPV.

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"If you know what causes a cancer, you can much better define what strategy to use to combat it."

About 350 000 people worldwide were diagnosed with oral cancer each year, said David Wong, oral pathology chief at the Harvard school of dental medicine.

It was very disfiguring, hard to treat, and half of all patients died within five years, a toll that hadn't changed much in two decades, he said.

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Smoking and heavy alcohol use were the chief causes, but about 15 percent of patients didn't have those risk factors, puzzling doctors.

The Hopkins research implicated a strain of HPV in some of those cases, suggesting it caused a unique type of oral cancer.

Approximately 40 million Americans are infected with HPV, a sexually transmitted virus that comes in over 80 strains.

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Most are benign; some cause the common wart, for instance. But about one percent of infected people have the HPV 16 strain that causes most cervical cancer - and HPV 16 is just what the new Hopkins study of oral cancers found, too.

Gillison tested head-and-neck tumours taken from 253 patients and detected HPV in 25 percent of them.

The virus was only in tumours in the tonsils and base of the tongue, and HPV-positive tumours tended to occur in nonsmokers who drank little alcohol.

More important, patients with HPV-positive tumours had a 59 percent lower chance of dying during the study.

But Gillison was still skeptical - just because the virus was in a tumour didn't mean it caused the cancer.

So, she gave the tissue samples to pathology specialists, who discovered that under a microscope, HPV-positive oral cancer had unique cellular characteristics almost identical to HPV-caused cervical cancer.

The next step: alcohol and tobacco both disable a gene called p53 that is supposed to fight cancer, and almost half of all oral cancers have specific alcohol- or tobacco-caused p53 mutations.

HPV, in contrast, could cause cervical cancer without stopping to mutate p53. Indeed, a gene check showed the HPV-positive tonsil cancer had far fewer p53 defects than HPV-negative tumours.

"With all of this, we were convinced," Gillison concluded.

The study didn't address how HPV was infecting people's throats, but Gillison said oral sex or something as simple as unwashed hands could explain it.

The bigger question was why a virus-caused tumour didn't appear as deadly as one caused by tobacco or alcohol.

Perhaps HPV-caused tumours didn't invade deep tissues and spread as quickly, meaning surgery or radiation could work better for those patients, Gillison speculated.

Whatever the reason, a virus gave oncologists a long-awaited new target in attacking oral cancer, said Harvard's Wong.

And, thanks to efforts at fighting cervical cancer, some experimental strategies are already under development.

The National Cancer Institute has funded Hopkins scientists, who are developing vaccine-like treatments that prime the immune system to recognise and attack HPV 16 in cervical tumours.

Now those scientists are expanding a planned clinical trial of the anti-cancer vaccine to include oral cancer patients, too. The clinical trial should begin within a year, said Gillison. - Sapa-AP

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