The Path To A Cure

It's the culmination of a lifetime of work for University of New Mexico professor Cosette Wheeler, and it could be the largest development in women’s health since the advent of the birth control pill. After studying the Human Papillomavirus (HPV) for two decades, she will likely see a breakthrough vaccine for the virus released to the public this year. The hope is that this vaccine could potentially prevent more than 80 percent of cervical cancer cases.

“HPV causes 99.7 percent of cervical cancer,” Wheeler says. “It's not just a link. It is actually the cause. And there's no other cancer in which [a single causative agent] is known.”

Wheeler began studying HPV in the '80s, before the virus, which has more than 100 strains, was understood. At the time, scientists didn’t know what the virus did, how many strains there were or that certain strains cause cervical cancer. “We didn't know anything,” Wheeler says. “Someone found HPV in a cervical cancer [case], and that's what started us working in that area.”

UNM’s House of Prevention Epidemiology, more commonly called the Hope Clinic, has been on the forefront of the vaccine’s study, with Wheeler as the lead researcher. More than a thousand women, mostly from the UNM area, have participated in trials, the latest results of which were released last Thursday. Findings show promising results: The vaccine may provide protection against more HPV strains than was expected, and it was found to be effective for at least four and a half years, the amount of time researchers have been following the results. Studies are ongoing.

The implications are staggering—for New Mexico, the nation and the world. “These vaccines would be able to protect women who have precancerous abnormalities from HPV that have no Pap smears,” Wheeler says.

What is HPV?

Human Papillomavirus refers to a group of viruses, including about 100 strains, more than 40 of which affect the genital tract and are primarily sexually transmitted. It is the most common kind of sexually transmitted infection. “They are like bacteria on our skin,” Wheeler says. “They are circulating in the sexual population, and the data shows that [on average] people have sex by the time they're 16.”

HPV often doesn't manifest symptoms or develops only mild symptoms, which can include low-grade or atypical abnormal Pap smears. According to the Center for Disease Control and Prevention's (CDC) website, most infections will clear up on their own. Condoms offer only moderate protection against HPV, because viral sites can be found anywhere on the pelvic area, and HPV is transferred via skin-to-skin contact. And so even though HPV cannot move through latex, condoms only protect the area they cover.

The CDC estimates that at least 50 percent of sexually active people will contract HPV at some point in their lives, and 20 million are presently infected. About 6.2 million people in the United States contract a new genital HPV infection each year, and at least 80 percent of women, according to the website, will acquire a genital HPV infection by the time they're 50.

In 2001, the Hope Clinic studied 4,000 sexually active women in New Mexico ages 18 to 40 who were reporting for routine Pap smears and found that 39 percent of them had HPV. “It shouldn't have the stigma that's associated with sexually transmitted disease or infection, like Gonorrhea or Chlamydia,” Wheeler says. “It's much more common. You almost can't help from getting it. [If] you have sex, you get it. That's the attitude that should be had when considering the vaccine.”

How Does the Vaccine Work?

The HPV vaccine is a single protein, which tricks the body by forming the shape of the virus, causing the body to make antibodies that then kill the virus. But unlike other vaccines, such as flu shots, the HPV vaccine is a synthetic shell that doesn't carry any of the virus' nucleic acid or DNA inside it. “There is absolutely no way you could get an infection from this vaccine,” says Norah Torrez-Martinez, Hope’s clinical operations manager. Common side effects include redness on the arm where the shot is given, sore arms and headaches, but that, Wheeler adds, would be true of any vaccine.

Today, the medical world copes with cervical cancer through Pap smear screenings, which can prevent almost all cases of cervical cancer. In the United States, between $3 and $5 billion a year are spent on Pap smears and treating abnormal Pap smears, Wheeler says. In countries that don’t have the infrastructure to provide Pap smears, women often die of cervical cancer.

The vaccine works by being administered in three shots over the course of six months. “You can manage to give people shots better than you can manage to have people who know how to read Pap smears, who can go get women who have problems and need treatment, etc.,” Wheeler says. “That complex sort of network that you need to manage abnormal Pap smears has a chance of being replaced someday for countries that probably never will have that capacity.”

Two companies, Merck and GlaxoSmithKline, have already produced HPV vaccines, though neither have yet been licensed by the Food and Drug Administration (FDA). Merck has submitted its vaccine for licensure, and the FDA will issue its decision on June 8, according to the New England Journal of Medicine. On its website, GlaxoSmithKline says it expects to submit its vaccine for licensure in the second quarter of this year, and though there’s no telling how things will go, the company expects its vaccine to be licensed in 2007.

The first clinical trials for the vaccine took place in 1997. That was the “phase one” trial for the Merck vaccine, Gardasil, and UNM and Indiana University were the only sites for the study, says Torrez-Martinez. For “phase two,” UNM tested Cervarix, GlaxoSmithKline’s vaccine, and were joined by 28 other sites in Canada, North America and South America. For “phase three,” which is ongoing and has not yet been unblinded, hundreds of sites around the world are participating.

Patients are required to visit the clinic for three to four years, a significant commitment, Torrez-Martinez says. At three of the nine visits, a patient is injected with either the HPV vaccine or a placebo. Patients give urine and blood samples, keep a diary on how they feel and receive pelvic exams over the course of their participation.

Wheeler says the vaccine does not have broad coverage against all the HPV types that cause cervical cancer. It has been shown to be effective against strains 16 and 18, which cause about 70 percent of cervical cancer cases. The new research shows that Cervarix also may provide some protection against two more strains, which, when combined with the others, cause more than 80 percent of cervical cancer cases. If more complex vaccines that could prevent all dangerous HPV strains are developed, then cervical cancer could be eliminated.

Impacting New Mexico

Typically, researchers are required to do only a small part of the work in testing and developing vaccines—meeting with patients, entering data or doing lab work. But the Hope Clinic’s researchers have performed all of those tasks. And although it’s taken nearly 10 years, the vaccine trials are finally coming to fruition.

“After all of this, what does it really mean?” Wheeler asks. “It only means something if people can get it.”

One potential road block to the vaccine being widely distributed is its cost. The vaccine is expensive, with some estimates ranging between $100 and $150 per shot, and three shots are required for it to work. Deborah Busemeyer, spokesperson for the state’s Department of Health, says the department will do its best to make the vaccine available to as many New Mexicans as possible.

New Mexico, she says, is a universal state, which means vaccines are free for its children. The federal government pays for children on Medicaid, uninsured or underinsured kids, and Native Americans, which comes out to about 70 percent of New Mexico’s kids. The state picks up the tab for the other 30 percent.

Once the vaccines are licensed, Busemeyer says, there will be a meeting of the federal Advisory Committee on Immunization Practices. If that panel recommends the vaccine to the Vaccine For Children Program, it could become part of the childhood medical regimen in New Mexico, possibly with middle school-aged girls as the primary recipients. The vaccine is predicted to be most effective before women begin having sex, Wheeler says.

But Martha Edmands, the director of public and governmental affairs at Planned Parenthood, says she sees trouble on the horizon. “The politics of teen sex are going to create huge problems with vaccination rates,” she says. “People who believe in abstinence-only aren’t going to have their girls vaccinated.”

But Wheeler says the moral arguments are moot. “The bottom line is, we believe doctors are going to recommend it.” Torrez-Martinez says she’s looking forward to the day when she can get her 10-year-old daughter vaccinated against HPV. “Then she’s protected from abnormal Pap smears for at least 4.5 years,” she says. “That’s a lot more than we had available to us.”