Work on Cervical Cancer Vaccine Puts NIH Duo in the Running for Major Award

Work on Cervical Cancer Vaccine Puts NIH Duo in the Running for Major Award

Washington Post
September 10, 2007

It started as one of those basic science projects, trying to understand the mysterious ways of a virus.

It ended with a discovery that led to a vaccine for the sexually transmitted virus that causes cervical cancer, the No. 2 killer of women worldwide.

The research that led to the breakthrough was conducted by two government scientists -- Douglas R. Lowy and John T. Schiller -- who have worked together for nearly 24 years. Their collaboration was made possible because of where they work -- a federal lab that is mostly free of commercial pressures and the academic red tape that goes with selling ideas to obtain research grants.

Lowy and Schiller are among 31 finalists for Service to America Medals, the awards sponsored by the nonprofit Partnership for Public Service to honor civil servants for their innovations and dedication. The award winners, including Federal Employee of the Year, will be announced Sept. 19 at a Washington gala.

For Lowy and Schiller, the honor of being a medal finalist in 2007, selected from nearly 600 nominations, is a reminder that most scientific research is a long-haul proposition. They are being recognized for a series of scientific discoveries that began in 1992.

Since then, they moved to other research, but found themselves still involved in their original project as others extended their findings in the large-scale clinical trials and studies needed before the vaccine could win federal approval for use by doctors. That approval was granted by the Food and Drug Administration in June 2006.

Lowy and Schiller work together at the National Institutes of Health, where Lowy is the lab chief and Schiller the senior investigator in the National Cancer Institute's Laboratory of Cellular Oncology. Wags like to joke that NIH stands for Not Invented Here, but Lowy and Schiller are immune to such teasing. They are the first and second inventors on government-owned patents for their discovery, making them eligible for limited royalties.

They began their research with a broad interest in the role of viruses in making cells grow abnormally and began to focus on human papillomavirus, or HPV, when other scientists provided evidence for HPV's link to cervical cancer.

But HPV was especially difficult to study, in part because it only grows in the skin or other body surfaces. Lowy and Schiller, however, found that 360 copies of the protein encoded by a single HPV gene could assemble into a particle that looks like the outer shell of the virus and that these protein particles could be mass-produced.

When these protein particles were injected into rabbits, their immune systems produced antibodies that could prevent the real tumor virus from infecting cells. "That was sort of the eureka moment," Schiller said.

The findings implied that a safe vaccine could be developed, because the protein particles did not contain the genes that cause cancer. "All you really need is this one protein," Lowy said.

Because they are laboratory-based researchers, Lowy and Schiller called upon clinical scientists at Johns Hopkins University to run early trials and validate that the vaccine was safe and induced a robust immune response in people.

Although some pharmaceutical companies had doubts whether the vaccine would stop a sexually transmitted disease, views began to shift in the mid-1990s. Merck and GlaxoSmithKline undertook large-scale human clinical trials that showed cancer-causing HPV infections could be prevented. Merck received its license in 2006 and is producing a vaccine for females ages 9 to 26. GlaxoSmithKline applied for its license this year.

The clinical trials have shown the vaccine is effective for at least four to five years. The National Cancer Institute is conducting independent trials on the vaccine, and Lowy and Schiller hope the vaccine proves to have a long-lasting protection and will someday be manufactured at lower cost for distribution in developing countries, where fewer women receive annual Pap smears to reduce their risk of cervical cancer.

Lowy, who has a medical degree, and Schiller, who has a doctorate in microbiology, prefer to share credit with others for their breakthrough. They emphasize that their work built upon decades of research by other scientists and was made possible through improvements in technology.

They also said their research was made much easier because of the freedom that NIH provides scientists. Because senior researchers have stable funding, they can jump into a project without having to spend time writing up justifications and applying for grants.

"You are given wide latitude on what you work on," Lowy said. "The assumption is that you will work on important problems."

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HPV Vaccine Flags Need for More Pap Tests

HPV Vaccine Flags Need for More Pap Tests
Posted on September 5, 2007, Printed on September 6, 2007

By Judy Norsigian and Heather Stephenson, Women's eNews

A little more than a year ago, the nation's first vaccine against some human papillomavirus (HPV) infections was released.

This medical progress against cervical cancer got swept up by fear-based marketing that helped to generate premature calls for government mandates.

"You could become one less life affected by cervical cancer" is the mantra in most of Merck's ads for its vaccine, called Gardasil. The ubiquitous marketing campaign may leave viewers thinking that cervical cancer is more prevalent than it really is.

Merck also lobbied behind the scenes to make its vaccine mandatory for school-age girls, quietly funding groups such as Women in Government that promoted mandatory vaccination bills in state legislatures. Such a mandate, if passed quickly, would have increased the firm's sales before a competitor's product -- soon to hit the market -- was available.

When Merck's funding was exposed, the tactic backfired, fanning suspicions that profit motives were overwhelming public health concerns.

Opposition came from other camps too. Some parents pointed to the new vaccine's side effects (which are usually minor and transient) and questioned whether it should be required. Social conservatives raised concern that the vaccine could lead to increased sexual activity among America's youth.

HPV vaccination has been approved for females ages 9 through 26 and appears to be most beneficial for girls with no prior sexual activity. Studies show that vaccination after virus exposure is only minimally effective. The vaccine is not recommended for pregnant women, anyone with moderate to severe acute illnesses or anyone with sensitivity to vaccine components.

All of this has left a number of questions simmering.

Would a Mandate Reduce Cervical Cancer?

The U.S. Centers for Disease Control and Prevention predict a 22 percent to 60 percent reduction in cervical cancer attributable to this vaccine. However, for these reductions to be realized, a high proportion of young women will have to be vaccinated. Even then, reductions in invasive cervical cancer won't be measurable for several decades.

Many believe mandates are premature. Gardasil appears safe and effective up to five years, the length of time studies have covered so far, and if its effects are as strong over the long term as early results suggest, then requiring and funding vaccination for school-age girls (with exceptions for families who opt out) may become the best way to ensure access and protection for all girls, regardless of class or race.

About 10,000 cases of cervical cancer will be diagnosed this year in the United States, and about 3,700 of these women will die from the disease.

Most who die of cervical cancer never had regular Pap tests. These screening tests can detect pre-cancerous tissue, which can be removed to prevent the development of cervical cancer.

In the United States, there are 6.6 cases of cervical cancer for every 100,000 white women and 10.5 cases for every 100,000 African American women. The racial disparity is due at least in part to women of color having less access to screening.

Globally, in regions where screening is much less common, the numbers are much worse. In areas of Africa, Central and South America, and Micronesia, there are more than 50 cases of cervical cancer per 100,000 women.

We don't know yet if requiring vaccination could reduce cervical cancer deaths and reduce racial and ethnic disparities in terms of HPV prevalence, cervical cancer incidence and cancer mortality. It is possible that women who do not get regular Pap screening and follow-up now will also be those least likely to be vaccinated, even with legislative mandates in place.

If there's one thing the discussions make clear, it's that we need to try harder on Pap tests. Cervical cancer used to be a leading cause of cancer deaths among U.S. women. But since the introduction of the Pap smear in the 1940s, those deaths have dropped about 75 percent, even as the population has grown.

What Does the HPV Vaccine Achieve?

HPV is the most common sexually transmitted infection in the United States, affecting about 1 in 4 women between 14 and 59. Exposure usually occurs within the first few years of sexual activity, but infections often go unrecognized because there may be no symptoms. The vast majority of HPV infections clear up on their own.

Worldwide, 70 percent of women who develop cervical cancer have been infected with either HPV 16 or HPV 18, two of the strains the Gardasil vaccine targets. But most women infected with even such "high-risk" strains of HPV will not develop cervical cancer.

In addition to effectively protecting against HPV 16 and HPV 18, Gardasil protects against types 6 and 11, two strains that can cause genital warts but not cervical cancer.

Cervarix, a vaccine that GlaxoSmithKline expects to introduce in the United States soon, also protects against HPV types 16 and 18, but not the strains that can cause genital warts. Both Gardasil and Cervarix may provide partial cross-protection against some additional HPV types.

Neither vaccine protects against all strains of HPV that can lead to cervical cancer. In addition, testing of Gardasil has shown that it is far less effective if women have been exposed to HPV before vaccination. This is one reason why vaccination of girls as young as 9 has been recommended.

Regular Pap tests and follow-up care are still needed, even for women who are vaccinated, because they may have prior exposure to HPV or may in the future become exposed to strains that are not covered by the vaccine.

It is worth noting that HPV vaccine trials have demonstrated only protection against HPV-related genital pre-cancers, not cancer.

Should HPV Vaccines Be Made Available to All?

Is spending public money on HPV vaccination of all girls and young women appropriate, when cash-strapped communities could put the funds to other uses? This may be the most difficult question of all.

It leads immediately to another question: Does Merck need to charge $360 per person for the vaccine as it does now? According to Glenn McGee of Albany Medical College, Merck could recoup in several years its development costs for this and other vaccines that never made it to market by charging one-tenth the current price (assuming that sales continue at the current rate).

Merck says it calculated the price taking into account research and development costs as well as what the vaccine could save in terms of HPV-related treatment expenses. It argues that the long-term cost savings justify the unusually high price for this vaccine. Other analyses (for example, a British Columbia Cancer Agency report) disagree with these calculations and conclude that the cost of vaccination greatly outweighs the amount saved by avoiding treatment of HPV-related disease.

As we consider how to proceed on HPV vaccination, a clear understanding of the research -- not marketing claims or lobbying funds -- needs to guide both our individual decisions and our public policy.

Judy Norsigian is the executive director of Our Bodies Ourselves. Heather Stephenson is the editor of "Our Bodies, Ourselves: A New Edition for A New Era" (Simon and Schuster, 2005); "Our Bodies, Ourselves: Menopause" (Simon and Schuster, 2006); and "Our Bodies, Ourselves: Pregnancy and Birth" (Simon and Schuster, forthcoming in 2008).

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Cervical Cancer Vaccine Stops Viruses Tied to Cervix Scourge

Cervical Cancer Vaccine Stops Viruses Tied to Cervix Scourge
August 30, 2007

If you watch Oxygen network, "Sex and the City" reruns or any programming geared to young women, you're bound to have seen the commercial for Gardasil, the new HPV vaccine. It features women professing to be "one less" victim of Human papillomavirus, a virus that is often sexually transmitted and can lead to cervical cancer.

In 2006, the Food and Drug Administration approved Gardasil, which is the first HPV vaccine to prevent four of the more than 100 strains of HPV in girls and women age 9 to 26.

Because cervical cancer will affect an estimated 11,150 women in 2007, according to the National Cancer Institute, many doctors and women in the at-risk demographic say the vaccination is a victory for prevention.

"In my opinion, for girls and women who've never had HPV, Gardasil can prevent four strains of HPV that cause 90% of genital warts and about 67% of cervical cancers," says Bronwyn Fitz, physician director of colposcopy services at Planned Parenthood of New York.

While the ideal age for the vaccination is 11 or 12, before girls are sexually active, doctors are pushing for women up to the age of 26 get the shot as a preventive measure.

But some observers are apprehensive about the pervasive marketing of the vaccine and wonder if the drug, which costs at least $120 for each of the three injections, is an unnecessary expense.

Elana, 26, of Manhattan, balked at the price. "If this is such an impactful thing, it should be affordable," she said. "There are tons of commercials and marketing campaigns, but what they don't tell you is you have to put aside money in order to afford that."

Kate, 23, of Manhattan said, "It's been pushed so heavily, I feel a little bit like I'm being sold the 'product.'" Still, last year, a pap smear found abnormal cells on Kate's cervix. The abnormalities turned out to be benign, but Kate intends to get a Gardasil vaccination soon. "Having been through a scare with it, I'm willing to take another measure." Kate's insurer, Aetna, will cover the vaccinations in full, she said.

Indeed, HPV is one of the most common sexually transmitted diseases. However, Planned Parenthood's Web site states that "most HPV infections go away within eight to 13 months" and Gardasil's Web site acknowledges an HPV infection sometimes goes away on its own.

Although Gardasil's Web site states in several places, "Gardasil may not fully protect everyone and does not prevent all types of cervical cancer, so it is important to continue regular cervical cancer screenings," some professionals are critical that the vaccine detracts attention from pap smears, which are comparatively cheaper.

"I'm annoyed at Merck [the drug company] for the way they've presented this," said Dr. Steven Goldstein, a professor of obstetrics and gynecology at New York University. He is concerned that Merck's advertising for Gardasil will lead women, especially young women, to believe they are immune to all forms of HPV and that they will not practice safe sex or keep up with visits to their gynecologist. He adds, "The people who need it the most aren't going to get it" due to the price.

Sigrid Fry-Revere, director of bioethics studies at the libertarian Cato Institute, is also skeptical. "The only reason Merck is marketing it so heavily is because this is where the money is," she said. In her opinion, "pap smears have all but eliminated the need for a vaccine," which she characterized as "experimental." She feels the FDA approval process was "rushed," and while she recognizes that no adverse side effects have come up, she thinks the samples in the trials are relatively small.

But Planned Parenthood's Fitz, disagrees. "I wouldn't call it 'experimental'." Fitz attests the vaccine offers an advantage that pap smears do not: the HPV vaccine prevents women from getting four strains of the virus, while pap smears only test whether the HPV infection has already occurred.

"If we could prevent infection altogether, that would be better," she said.

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Twins Help Study to Single out Cervical Cancer Risks

Twins Help Study to Single out Cervical Cancer Risks
August 20, 2007

LEE and Sharon Naylor might not look the same, but these Melbourne twins are identical in their support of a new study linked to cervical cancer.

The Victorian pilot project will use twins to investigate the human papilloma virus (HPV), an infection that can lead to cervical cancer.

Researchers want to find out why the virus, which is extremely common among the sexually active, causes no symptoms in some women, but disease in others.

Study co-ordinator Professor Suzanne Garland, of the Royal Women's Hospital, said the work would help scientists understand what made some women more at risk of cancer than others.

"We know that smoking increases a woman's risk of disease, but we don't know what are the other factors," she said. "So we are using twins to help us tease out the environmental from the genetic."

The study is seeking the involvement of female twins over the age of 30. Researchers will look at their Pap smear history and ask participants to complete a questionnaire.

Dr Lee Naylor, a former Olympic athlete, said she and Sharon were always happy to take part in twin studies. "If we can assist the population's general health, then I'm all for it."

And as mothers, the twins hope their involvement may also help improve the lives of their children. "As a parent, any way you can look after your kids, you do," Dr Naylor said.

Cervical cancer is the second most common cause of cancer death in women around the world. In 2004, there were 212 deaths from the cancer in Australia, including 47 in Victoria.

The HPV study is a joint project of the Royal Women's microbiology and infectious diseases unit, the Australian Twin Registry and the University of Melbourne.

National Science Week runs until Sunday. See scienceweek.info.au for the full program.

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