The War on HPV

Amelia Togba-Addy, a nurse at Emory Crawford Long Hospital in Atlanta, had always been in good health. But last October her gynecologist called with disturbing news: Togba-Addy's latest Pap smear showed abnormal cells on her cervix. First, doctors removed the suspicious tissue and examined it under a microscope--then they diagnosed Togba-Addy with cervical cancer. In January, she had a hysterectomy. "Even though the doctor says she believes I'm cured and my faith tells me I'm cured, there's still a little part of me that worries," says Togba-Addy, 39. "Before all of this, I didn't even think about cervical cancer."

Few women ever do. Until the Pap smear was introduced in the 1940s, cervical cancer was the No. 1 cancer killer among women. Since then, routine screenings--which detect damaged cells before they become cancerous--have made enormous strides. Over the past 50 years, deaths in the United States have plummeted by more than 70 percent to less than 5,000 a year. But the disease is far from eradicated. Developing countries, where good health care is either inaccessible or unavailable, account for more than 80 percent of deaths from cervical cancer, according to the 2003 World Cancer Report. Every year, half a million women are diagnosed with the cancer and close to 250,000 die.

The disease, however, has a unique and fortuitous characteristic that scientists have exploited in their battle against it: cervical cancer is caused by the human papillomavirus (HPV), a sexually transmitted infection. In June, the U.S. Food and Drug Administration is expected to approve a new vaccine that prevents key strains of HPV; if enough women receive the inoculation, tens of thousands of lives might one day be saved. "This is the first vaccine designed to strike at the root of a cancer," says Dr. Martin Murphy, executive editor of The Oncologist. "Boy, is this a new era."

HPV is one of the most common sexually transmitted infections on the planet--as many as 80 percent of women will be exposed to it at some point in their lives. More often than not, the virus causes no symptoms, is harmless and goes away on its own. Most people don't even know they have it. But certain varieties of HPV (there are about 100 altogether) are particularly aggressive, and two of them--HPV 16 and 18--cause 70 percent of all cervical cancers. Caught early, the disease can be treated with surgery and, if necessary, chemotherapy. But untreated in its advanced stages, it is a painful, gruesome and formidable enemy. In the end, "women bleed to death," says Dr. Diane Harper, of Dartmouth Medical School, and a leading HPV-vaccine investigator.

Under the microscope, HPV looks like a tiny molecular golf ball, with a tough outer shell surrounding a core of infectious viral material. It is a critical ingredient in the shell, a protein called L1, that makes vaccine production possible. Isolated on its own in a petri dish, L1 has acrobatic talent, assembling itself into what scientists call a "viruslike particle" that looks just like HPV, but has "none of the bad stuff inside," says Dr. Eliav Barr, head of the HPV-vaccine program at Merck. Injected into the body, the particles act as decoys, tricking the immune system into recognizing them as HPV. Later, if the real virus hits, the body sees trouble, then assaults and neutralizes the invaders.

Two vaccines, manufactured by Merck and competitor GlaxoSmithKline, have shown remarkable results in clinical trials: close to 100 percent protection against HPV 16 and 18. In rare instances, the strains can cause penile and anal cancer in men; Merck's vaccine also protects against two other types of HPV that cause genital warts in both males and females. Nobody knows exactly how long the vaccines will be effective and when, or if, boosters will be needed. But Merck plans to release five-year data soon and, in April, Glaxo reported that four and half years after receiving the vaccine, trial participants continued to show high levels of antibodies against the virus. "We're very encouraged," says Dr. Gary Dubin, Glaxo's head of clinical development.

So is Sarina Araujo, 40, of the National Cervical Cancer Coalition. After a DNA test came back positive for HPV in 2001, doctors removed several precancerous lesions from Araujo's cervix and she's being closely monitored today. "This is a very strong, persistent virus and my body can't seem to fight it off," she says. The CDC's vaccine advisory committee will make a recommendation on Merck's vaccine after the FDA decision in June. Glaxo filed for approval in Europe in March, and says they'll file for approval in the United States by the end of the year. The precise guidelines in terms of age--the vaccine has been tested in 9- to 26-year-old females--haven't been finalized, says the CDC's Lauri Markowitz. (Tests are still ongoing in males and in females older than 26.) But the committee is considering recommending it for 11- to 12-year-old girls so they can be protected before they become sexually active. Abstinence groups like the Family Research Council will be watching closely. While not opposed to the vaccine, the council believes it should be voluntary and include a warning about the risks of sexual activity. Araujo just wants her three teenage daughters safe: "If you can prevent cancer, how could you not want your children vaccinated?"

Vaccination cannot, however, save the lives of women who have already developed cervical cancer, which strikes particularly hard in South Asia, Latin America and sub-Saharan Africa. At Groote Schuur Hospital in Cape Town, Dr. Lyn Denny treats 200 women a year with the disease, most of them in advanced stages. Pap smears are available, says Denny, but the test is not widely used, especially in poorer populations where the HIV epidemic diverts attention and resources. Because the cancer is slow-growing--it can take more than a decade to develop--women are hit in the prime of life, says Jackie Sherris, of PATH, a nonprofit global health organization. They're leaders in their communities, raising children, caring for family members. "There are countries where Ob-Gyn wards are filled with women with cervical cancer and they're dying," says Sherris. "It's very important to protect them."

To improve the odds, PATH has been testing one-stop screening and treatment programs overseas. Clinicians look for precancerous lesions, then freeze and obliterate the abnormal cells on the spot. PATH is working with partners to produce a cheaper version of the existing DNA test for HPV, which is used in combination with Pap smears in the United States. And they are assessing the logistical and economic challenges of vaccination in developing countries.

And then there's the effort led by Dr. Robert Garcea at the University of Colorado. Last summer Garcea and his team won a $3.5 million Grand Challenges in Global Health award from the Bill & Melinda Gates Foundation. The challenge: to develop an inexpensive vaccine that would protect against HPV and eradicate the virus in women who are already infected. And they hope to make the vaccine out of powder so that it doesn't need refrigeration and can be easily transported to remote villages. "It's never been done before," says Garcea. "If it works, it'll be great."

It is tempting to imagine a world without cervical cancer. "I think we should always be asking the question, Can we get rid of a scourge for future generations?" says Dr. Bill Foege, the global health pioneer who helped stamp out smallpox and is now a senior fellow at the Gates Foundation. "If we can, then it's worth all the heartache and the difficulties." With tens of thousands of women still dying, it's too early to talk about eradication, says Foege. But it's not too soon to dream.