• 11/12/2007
  • Boston, MA
  • Scott Allen
  • Boston Globe

Scientists are only beginning to discover the hidden role of some viruses and bacteria

The almond-shaped lump on Brian Hill’s throat didn’t make sense to him. The doctor said it was a symptom of advanced oral cancer, but Hill had never smoked a cigarette or chewed a plug of tobacco, considered the main causes of the disease when he was diagnosed in 1997. So why was it there?

Not until four years later did Hill get an explanation for his brush with death: a microbe called human papilloma virus-16 had apparently moved into his tonsils, gradually turning normal cells into cancer. Hill, now 59, had become part of a wave of relatively young nonsmokers who contracted oral cancer from the sexually transmitted virus, fueling an overall increase in new cases.

Viruses such as human papilloma may be the most overlooked bad guys in the war on cancer, silent invaders that contribute to more than a dozen malignancies and may cause 15 percent of the cancer cases worldwide each year.

“What we know about HPV-16 as a cancer causer is just the tip of the iceberg,” said Hill, founder of the Oral Cancer Foundation, which funds research for a disease that strikes 34,000 Americans annually and is caused by the same virus that can lead to cancers of the cervix, vulva, anus, and penis.

The cancer toll from germs – both viruses and bacteria – may turn out to be higher as researchers discover more of these elusive microbes and how they do their grim work. Currently, scientists can’t even estimate how many viruses afflict human beings, let alone how they impact human health. Some suspect that unknown viruses may be causing cancers that are now blamed on something else, much the way doctors believed that stress and spicy foods caused stomach ulcers until scientists discovered the real culprit – bacteria – in 1982.

“There are a lot of infectious diseases that we just don’t know about, including a lot of cancers,” said Dr. Matthew Meyerson, a cancer genetics researcher at the Dana-Farber Cancer Institute in Boston and the Broad Institute of Cambridge. Unfortunately, he said scientists have not come up with a simple way to identify unknown viruses lurking inside human genes.

But it’s already clear that cancer is more contagious than most people realize: everyday acts of intimacy such as kissing and lovemaking potentially transmit viruses from one person to the next that, for an unlucky minority, will cause cancer years later as the genetic damage to cells slowly mounts. For instance, people who have oral sex with six or more partners triple their risk of developing oral cancer due to the transmission of the papilloma virus, according to a recent study from Johns Hopkins University in Baltimore.

Yet, medical advice on how to prevent cancer usually centers on avoiding tobacco, sunlight, cancer-causing foods, and environmental pollution, with only secondary mention of the need for protection against infections by cancer-causing viruses.

“We worry about ‘Should I eat those french fries or that apple?’ but we don’t manage our infections. I don’t say, ‘I think I’ll have a little less Epstein-Barr virus today,’ ” said Dr. Julie Parsonnet, a researcher at Stanford Comprehensive Cancer Center in California who focuses on infectious diseases. “We are probably focusing on the wrong thing.”

Ultimately, Parsonnet believes that infections from viruses and bacteria combined account for at least a quarter of cancers and more in developing countries where untreated infections are more common.

However, Parsonnet hopes the advent of the vaccine against cervical cancer, Gardasil, in 2006, may have begun to raise awareness. The maker, Merck & Co., ran national television advertisements that depicted average women expressing their surprise that cancer could be brought on by a viral infection. “That for the first time brought infections to the public mind as a cause of cancer,” Parsonnet said.

Scientists suspected long ago that cancer could be an infectious disease: 19th-century physicians observed that cervical cancer was common among prostitutes and rare among nuns, suggesting the disease was spread through sex. But it wasn’t until the last 50 years that researchers began to draw the direct connection between viruses – organisms that need to get inside healthy cells in order to survive – and the nation’s second leading killer. Even now, researchers are still figuring out exactly how the viruses cause cancer.

The human papilloma virus makes proteins that corrupt cells inside body openings such as the mouth and vagina, causing the cells to live longer and reproduce more frequently. Unchecked, the genetically defective cells can grow and spread, disfiguring and potentially killing its victims.

But only one-third of the more than 100 strains of papilloma have been linked to cancer, and even those trigger cancer in a tiny fraction of infected people: More than 20 million women will be infected with papilloma virus this year, for instance, but only about 11,000 will be diagnosed with cervical cancer.

A second group of cancer-causing viruses, hepatitis B and C, attack the liver, where they take over healthy cells and also cause inflammation that further damages the cells. Millions of people carry these viruses with virtually no symptoms, but the 10 percent of patients who suffer chronic liver inflammation have an increased chance of developing cancer, cirrhosis, or liver failure.

Viruses often prey on people already suffering from another disease that has weakened their immune systems, making them more vulnerable. The Kaposi sarcoma associated herpesvirus is best known in this country for striking HIV patients, causing widespread skin lesions and sometimes death when the cancer spreads to the lungs.

The Kaposi virus illustrates how viruses can cause cancer without being detected: In addition to taking over some cells to use as “hosts,” the Kaposi virus quietly kills neighboring cells, allowing cancer to spread without any genetic “fingerprint” left behind. Dr. Preet Chaudhary, the University of Pittsburgh medical school researcher who discovered Kaposi’s cell-killing ways, believes that other viruses may do the same thing, but no one has noticed.

“It is possible that the actual cancers that are linked to viral infections are much more common than we realized,” said Chaudhary.

Scientists don’t know why different viruses are so selective in causing cancer, but Parsonnet believes the answer lies in the complex relationship between humans and the viruses inside them. The difference between a harmless virus and a deadly infection, she said, may come down to very specific details, or a cascade of unconnected events. “Maybe herpes causes cancer but only if you previously had CMV (cytomegalovirus) and an exposure to hepatitis A before you were three,” she speculated.

Meyerson of Dana-Farber said it may be time for a systematic approach to studying cancer-causing viruses. The Human Genome Project, which identified the 25,000 or so human genes, could help researchers find microbial invaders in human tissue and fluids: If scientists find genes that aren’t in the genome, they must be from a nonhuman source such as viruses or bacteria.

“Once we find the first new pathogen with this approach, the field will explode,” Meyerson predicts.

In the meantime, oral cancer survivor Hill and his wife get tested regularly to see if the papilloma virus has returned, and he wants health officials to do more to fight viruses now.

Hill’s California-based Oral Cancer Foundation (www.oralcancer.org) is pushing to get the new cervical cancer vaccine, which protects girls against HPV-16 and HPV-18, to be offered to boys as well – something the vaccine makers are investigating. It’s possible, he said, to eradicate one major cancer-causing virus a generation from now. “We must act now.”