How cow warts, clergy sex surveys moved along cervical cancer vaccine

Jun 9 2006

The creation of a successful vaccine against cervical cancer, approved today by the U.S. Food and Drug Administration, is the culmination of research that occurred thanks not only to scientists and physicians, but also to generous farmers and veterinarians, priests and nuns willing to tell all - and some very patient cows.

At the University of Rochester Medical Center, the initial research more than 20 years ago included visits to veterinarians and meat-packaging plants in Upstate New York to collect scrapings from "prized" cow warts, and surveys of people unlikely to be infected with a sexually transmitted disease - priests and nuns who had taken a vow of celibacy.

The work with the cows, the warts, the nuns and the priests illustrates how basic research can pay off in big and unexpected ways. The research by a trio of University of Rochester virologists - William Bonnez, M.D., Richard Reichman, M.D., and Robert Rose, Ph.D. - helped bring about the cervical cancer vaccine, poised to prevent cancer in thousands of people. The University is one of several institutions in whose laboratories work on an HPV vaccine blossomed. Rochester's contribution is recognized with a patent issued by the European Patent Office and by royalty agreements with the companies commercializing the vaccine.

The research project in Rochester began with an effort to develop a blood test to detect infection by a class of viruses known as human papillomaviruses or HPV, which cause warts as well as cervical cancer. To do so, the researchers needed large amounts of papillomavirus - and while there are plenty of warts in this world, finding people willing to collect and analyze them is quite a different story. So as a starting point the team turned to bovine papillomavirus or BPV in cows, and Bonnez found himself visiting veterinarians and others with access to cows with warts, seeking samples.

In the world of warts, cows offer a particularly plentiful lode of papillomavirus, Bonnez said, because they are particularly rich in viral particles. Many other warts, such as genital warts in humans, don't provide enough viral particles.

The trips to the countryside were successful - Bonnez ultimately collected enough cow warts and still keeps a stash in his laboratory freezer - and the research moved ahead. The next step involved assessing the test, and doctors needed a large control group of adults who were unlikely to have been infected with genital HPV. So the group turned to area nuns and priests who allowed themselves to be polled about their sex lives and who donated blood samples. (Clergy have been crucial to other Rochester research projects as well; several have volunteered to test HIV vaccines, for instance.)

A few years into the project, the scientists faced difficulty improving their blood test using BPV, so they scrapped the cow warts and learned to grow human HPV in the laboratory. Soon after that they discovered that the three-dimensional outer shell of the virus was crucial to creating an immune response that could prevent infection.

The scientists then turned their attention to determining how to make a safe, non-infectious form of the viral coating, and that led them to figure out how to make harmless virus-like particles (VLPs) to trigger the same immune response. They did this by putting an HPV gene into insect cells using a virus called baculovirus, which infects insects; the HPV gene then produces VLPs that mimic the shape of real HPV particles. The team made VLPs of the specific cancer-causing strains of HPV and showed that they protected against the disease. VLPs are crucial to the vaccine approved today by the FDA, as well as another cervical cancer vaccine in development; both protect against multiple strains of the virus.

The new vaccine is given as a series of three shots administered a few months apart. Most doctors say the vaccine needs to be given before a person becomes sexually active to do the most good.

HPV causes about 9,700 new cases of cervical cancer in women in the United States annually, and about 3,900 women in the nation die of the disease every year. The toll is much worse in other parts of the world, where Pap smears to detect the disease in its earliest stages are not widely available. In some parts of the world, cervical cancer is the leading cause of death by cancer in women - doctors estimate that more than 230,000 women around the globe every year die from the disease.

In the United States, more than 15,000 people every day, or about 5.5 million people a year, get sexually transmitted HPV infections from their partners. About three out of every four sexually active people will get an HPV infection at some point during their lifetime; in some age groups, such as sexually active men and women under the age of 30, doctors estimate that 40 percent of people are currently infected.

Most people fight off the virus and never even know they were infected. Others have warts or abnormal cell growth known as dysplasias. In the most serious cases, it progresses to cervical cancer. Two types of HPV, type 16 and type 18, cause about 70 percent of cervical cancers, and those are the types that the new vaccine is designed to prevent.

While the new vaccine is certainly great news, there are still millions of people infected with the virus. That's why Reichman, Rose, Bonnez and many other researchers continue to do research on HPV. Bonnez, for instance, is part of a federally funded network of research centers that tests drugs against viruses. In the last 15 years he has evaluated more than two dozens drugs to treat HPV. Rose is exploring new methods to treat a person once he or she is infected.

The Rochester team, based in the Infectious Diseases Division of the Department of Medicine, makes up one of several laboratories whose work helped bring about such a vaccine. In addition to pharmaceutical giant Merck, which received approval from FDA to market its vaccine product, GlaxoSmithKline also has a product in development. Other institutions that have contributed include the National Institutes of Health, Georgetown University, and the University of Queensland in Australia.