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3-Dose Vaccine Declares War on HPV

The three letters meant nothing to Allison Walker two years ago.

But a phone call from her sister about a three-dose vaccine under study at MCG would change that and could potentially save her young daughter’s life.

“I had never really heard of HPV before my sister mentioned the vaccine study to me,” Ms. Walker says of the human papillomavirus, the most common sexually transmitted infection in the country and the major cause of cervical cancer.

Ms. Walker’s daughter, Joan, was just 16 at the time—much too young to worry about a sexually transmitted infection or cervical cancer, she thought.

“I was more hesitant about her getting the vaccine from the standpoint of it being new and not on the market yet,” Ms. Walker says. “Of course, not wanting to encourage her to have unprotected sex because she might be protected from HPV was a factor, too.”

Her own research and reasoning eventually prevailed, and Joan was enrolled in one of many HPV vaccine studies at MCG.

The vaccine under study in her case—called quadrivalent because it prevents infection from four strains of HPV—was Gardasil. Because MCG was one of the first testing sites for the vaccine, study patients such as Joan were among the first to receive the preventive treatment.

Over 12,000 women age 16–26 from 13 countries participated in the Gardasil study. Each woman was injected with either the vaccine or a placebo three times—on day one, in month two and in month six of the study. In February 2006, the independent Data and Safety Monitoring Board recommended terminating the clinical trials so young women on placebo could also receive Gardasil. The drug received final approval from the Food and Drug Administration June 8, 2006.

Gardasil works by mimicking HPV. The vaccine contains proteins that form virus-like particles that assemble into a hollow sphere that looks like the protective coating for HPV 6, 11, 16 and 18. Since this sphere lacks the actual viral DNA on the inside, it cannot cause HPV. But the body is tricked into making antibodies to protect against the real thing, says Dr. Daron Ferris, family medicine physician and director of the MCG Gynecologic Cancer Prevention Center.

Types 16 and 18 of HPV cause about 70 percent of HPV-related cervical cancer cases. HPV types 6 and 11 cause about 90 percent of genital wart cases. Cervical cancer, caused almost exclusively by HPV, is the third most common cause of cancer death among women worldwide. More than 270,000 women died of cervical cancer worldwide in 2002.

“The study of this experimental protective vaccine in adolescents took us to the next step,” Dr. Ferris says. “We hope parents realize that, one day, their children will be sexually active. We must give this vaccine prior to individuals initiating intercourse; that’s why we selected such a young age group.”

The Centers for Disease Control and Prevention recommends the vaccine as early as possible to help reduce the incidence of cervical cancer and reduce the transmission HPV.

‘The study took us to the next step.’

Hurdles have included a lack of public understanding that HPV causes cervical cancer and that nearly 80 percent of females will contract it in their lifetime, Dr. Ferris says. Other obstacles include kids’ aversion to shots and the cost of the vaccine, which can exceed $360 for three doses, plus the cost of office visits.

One proposed way to lower the cost and to educate the public is to mandate Gardasil vaccination for girls entering school, similar to the required vaccinations against mumps, measles, rubella and hepatitis.

Several states, including New Hampshire and Alaska, have implemented public programs that supply the vaccine free to girls age 11-18. Sixteen other states have legislation pending that could require vaccination before girls enter school. Most of those bills would allow parents to opt their children out of the program for religious or medical reasons, according to the National Conference of State Legislatures.

Of course, there are still unknowns about the vaccine, Dr. Ferris says, including how long it will be effective. But there’s only one way to answer questions: “We need further study,” he says.

Another question involves the vaccine’s efficacy in men. Because both men and women are carriers of HPV, both need to be vaccinated to eradicate the disease. Studies under way will ideally determine whether the vaccine is effective in men, Dr. Ferris says.

New studies are also under way at MCG to compare Gardasil to an experimental 9-valet HPV vaccine, which protects against nine types of HPV—6 and 11, related to genital warts, and 16, 18, and 5, other HPV types associated with an increased risk of severe pre-cancerous cervical dysplasia and cervical cancer.

“The placebo for that study is actually Gardasil,” Dr. Ferris says, “so every study patient is getting some form of the vaccine.”

The virus is incurable, but Pap smears alert physicians to the precancerous cervical changes that can result. “In the beginning, women usually have mild precancerous changes. The good news is, most of the time, these mild changes go away on their own and we don’t have to do any treatment other than following patients closely,” says Dr. Ferris.

If cervical cells develop moderate to severe changes—considered true cancer pre-cursors—women will most likely undergo a colposcopy, which allows a closer inspection of the cervix. Pre-cancerous changes are also treated by removing the cervix’s mucus-secreting tissue, but potential side effects include reduced fertility and increased risk of giving birth prematurely.

“By women being vaccinated against HPV, we could dramatically reduce the number of women who require surgery and reduce the number of women who develop cervical cancer,” Dr. Ferris says.

That was the deciding factor for Ms. Walker. “Her health and well-being superceded any doubts I had about enrolling her in the study,” she says. “Joan (now 18) has since mentioned it to a lot of her friends and they’re interested in the vaccine, too.”

--Jennifer Hilliard