Another HPV vaccine, approval for boys spark new questions

By Liz DeCarlo
Monday, January 04, 2010

As a gynecologic oncologist, Dr. Diljeet Singh is on the front lines treating women with the devastating effects of cervical cancer. So when a vaccine to prevent Human Papillomavirus (HPV), which causes most cervical cancers, was approved for use in the United States, she was thrilled.

"I'm an oncologist, so to me preventing cancer is key," says Singh, co-director of the ovarian cancer early detection program at Northwestern Memorial Hospital.

Dr. Diana Zuckerman also admits to being thrilled when Gardasil was approved to vaccinate girls against HPV. Zuckerman, president of the National Research Center for Women & Families in Washington, D.C., says since then she has analyzed reams of research and attended more meetings concerning the vaccine than she can even describe.

preview_HPV And for her and other staff members at her organization, whose sole purpose is to provide unbiased analysis of current research, the initial excitement has turned into skepticism about the wonders of the vaccine.

"We started out quite enthusiastic about Gardasil for girls. We've become less enthusiastic because we think the manufacturer is not being forthcoming about how long it lasts," Zuckerman says. "And it's so expensive, the most expensive vaccine ever sold in this country, so you want to make sure it lasts."

HPV is the name for a group of viruses that cause cervical cancer and genital warts. There are more than 120 types of HPV and as many as 40 of them are spread through sexual contact, according to the National Research Center for Women & Families. Many of the approximately 6 million people who are infected with genital HPV each year in the United States have no symptoms and don't know they are infected and 90 percent of cases clear up on their own without treatment. Not all HPV causes cancer, but 99 percent of cervical cancer can be traced to infection with a strain of HPV.

Controversy over the vaccines

The controversy over the safety and effectiveness of the HPV vaccine has ramped up in recent months with the approval in the U.S. of a second anti-cancer vaccine, Cervarix, and with the Centers for Disease Control and Prevention's approval of Gardasil for boys as well as girls.

Now parents of tweens and teens are slogging through Internet research and discussions with doctors to decide whether or not to vaccinate their children. At the same time, many doctors are wading through the same onslaught of information for and against the vaccines.

Angie Brocato of Darien remembers her doctor bringing up the vaccine when she brought her daughter in for a checkup at age 12. She'd done some research on the vaccine and decided she wasn't ready to vaccinate her daughter without more information.

A year later, when she brought her daughter in for another checkup, the discussion again turned to the HPV vaccine. But this time it was her doctor who told Brocato that, based on what she had heard about the vaccine, she couldn't in good conscience recommend it.

"We had basically said we weren't going to, I still don't think we'll get it," Brocato remembers. "And she said that she wasn't comfortable with it either at this point."

Brocato, who has a 13-year-old daughter and an 11-year-old son, is just one of many parents who want to do the best thing to care for their children, but who aren't sure what the right answer is. However, many national organizations, such as the American Academy of Pediatrics and the Centers for Disease Control, say the decision is easy-the vaccines, both Cervarix and Gardasil, are not only safe but can effectively eliminate the virus that causes almost all cases of cervical cancer.

"This is a very clearly needed vaccine for adolescent girls, reducing their lifetime risk of cervical cancer and it is very important as a preventive measure for the health of all women," says Dr. Joseph Bocchini, chairperson of the AAP's committee on infectious diseases and chairman of the Department of Pediatrics at Louisiana State University Health Sciences Center in Shreveport.

Who's actually recommending?

But some parents, and experts, think Gardasil has been so heavily marketed that a doctor's recommendation isn't enough to go on when considering the vaccine for their children. Because vaccines in the United States are created by companies whose goal is to make a profit, it's not always easy to determine objectively the value of a specific vaccine.

"Parents have to remember that people are selling this product and, like any product that's being sold, people have a vested interest in selling their product and making money and that puts parents in a difficult spot when deciding," Zuckerman says. "There's a lot of hype-the ads would make you think your daughter will get cervical cancer unless she gets this vaccine. But cervical cancer is still a pretty rare cancer in this country and the vaccine is, at most, 70 percent effective and probably less over time."

How long does it last?

Part of the controversy with the HPV vaccines revolves around how long the vaccines actually provide immunity. Because both Gardasil and Cervarix have been around for less than 10 years, it's not known if the immunity from HPV lasts indefinitely or if it wanes over time. Glaxo, which manufactures Cervarix, has distributed more than 7 million doses of the vaccine in other countries and has tracked immunity for the 6.4 years since vaccinations started. While they will continue to track immunity, current research shows that immunity continues for at least that length of time, says Jeff McLaughlin, spokesperson at Glaxo.

Merck, the manufacturer of Gardasil, has also tracked the ongoing immunity provided by the vaccine. At this point Gardisal shows immunity for five years, and ongoing studies will continue, says Jennifer Allen Woodruff, spokesperson for Merck. In one study, a challenge dose was given to women five years after receiving the vaccine to check immune response. Woodruff says this dose is given to check if immune memory is evident at that point because studies can't expose women to the actual virus.

"We have seen what is called immune memory with Gardasil, and that's considered to be a hallmark of long-term value for the vaccine," Woodruff says. At this point there is no indication that a booster shot would be needed, she says.

Zuckerman says it's not quite that clear-cut. "We're particularly concerned about Gardasil, not Cervarix, because in the one study Merck did about girls and young women, they gave a challenge dose of the vaccine at 60 months and then they measured their antibodies a short time later," she says. "To us, that looks like a booster shot. ... At three years, it looks like some of the protection is wearing off. In contrast, Cervarix is working longer than six years."

But the AAP's Bocchini says it's not unusual for vaccine immunity to wane over time. "These are new vaccines, so the thing we don't know is how long the immune response will last to enable the vaccines to remain effective," he says. "We have data out to at least six years and the vaccines remain effective at least six years, but longer than that we don't know. We don't know whether immunity will be lifelong or will require a booster."

He says it's important to give the shot early, even if a booster might be needed later. "It's really important to still give this vaccine prior to the onset of sexual activity."

Safety concerns

How long the vaccine lasts isn't the only concern for parents.

Recent media reports about girls who contracted fatal or debilitating illnesses such as Guillain-Barre Syndrome after receiving the vaccine have created Internet storms as parents react to the possibility that the vaccine isn't completely safe.

But many of the experts in favor of the vaccine point out that no studies have linked GBS to the vaccine, and the number of people contracting those illnesses are the same whether individuals are vaccinated or not.

"Since we give this vaccine to large numbers of patients, when an event occurs after vaccines, we have to determine if the vaccine caused it or if it occurred by chance," Bocchini says. "At this point, the events that have occurred have been at a frequency that is no greater than we would expect in the general population. Although we have to continue to monitor for safety issues, there is no safety issue that has come up to cause concern about either vaccine."

Singh also thinks cautionary stories in the media haven't stood up to investigation.

"When most of these stories are really followed down, they haven't clearly connected the vaccine to someone dying of something," she says, noting that no vaccine comes without risk, so the decision to vaccinate comes down to evaluating whether or not the benefits outweigh the risks. When it comes to preventing cancer, she says the benefits of either vaccine outweigh the possibility of any rare complications.

Another part of the controversy, Singh says, involves the fact that these vaccines are for sexually transmitted diseases, and many parents of tweens aren't ready to tackle the issue of their children's sexuality.

"The thing I find fascinating about this discussion, we give Hepatitis B (vaccines) to babies when they're born. You get Hep B from sex or needles. Nobody says, my baby's been vaccinated, that means he or she will run out and have sex because she had (the vaccine)," Singh says. But some parents don't want their children to be overly confident about their level of protection from the vaccine once they become sexually active.

Angie Brocato admits to thinking about future attitudes when deciding whether to vaccinate her daughter. "I didn't want her to have any kind of false security over so-called safe sex. I don't want these girls to think they've got this shot and they're not subject to gonorrhea or HIV, and this shot only takes care of a few strands of one particular disease."

Zuckerman, who agrees the vaccines appear to prevent about 70 percent of HPVs, also notes that 30 percent of the viruses are not covered. "At best, it's an imperfect vaccine."

Vaccinating boys

With the recent approval of Gardasil for boys, parents need to have even more discussions with their doctors. In October, the CDC approved Gardasil for "permissive use" in males. It stopped short of recommending it for boys, leaving the decision to parents and doctors. Gardasil provides protection for boys from HPV-related genital warts.

"If you vaccinate all girls and boys, yes, it'll cost twice as much, but ... if you think about, that's how the virus is passed around, you get herd immunity," Singh says. "And genital warts are a drag. If we can affect boys' protection, why not? Plus it gets rid of the stigma, of making it a girls' problem."

But the issue of how long the vaccine provides immunity is just as critical for boys, Zuckerman says, and it makes the decision to vaccinate even less clear-cut. "We don't think 12-year-old boys are at a big risk of genital warts.

The risk gets a lot higher when they get older," she says. "We don't think most families are going to want to vaccinate their boys, at $400 a vaccine every few years, to protect against genital warts."

Making the decision

While some other states have mandated the vaccine, in Illinois the decision to vaccinate comes down to the parent's choice. Deciding whether to vaccinate using Gardasil or Cervarix also rests with parents and their doctors.

While the AAP recommends children receive the vaccine at ages 11 or 12, Zuckerman says a wait-and-see approach regarding the vaccines won't hurt.

"For those who are a little concerned and would like to know more before they vaccinate, it appears that delaying vaccination for a few years is not a really big problem, but a sexually active teen should get pap smears."
All the experts agree that whether children are vaccinated or not, pap smears, once they become sexually active, remain a key element in preventing cervical cancer and shouldn't be overlooked in the fight against the disease.

Singh also recommends that parents who aren't getting the answers they need from their pediatrician regarding the vaccines should continue to ask the questions until they're comfortable with their decision. "Talk to your OB/GYN. Seek out other information," she says. "There's too much information out there in some ways, but people can try to direct you towards good vaccination information."

As a gynecologic oncologist, Dr. Diljeet Singh is on the front lines treating women with the devastating effects of cervical cancer. So when a vaccine to prevent Human Papillomavirus (HPV), which causes most cervical cancers, was approved for use in the United States, she was thrilled.
"I'm an oncologist, so to me preventing cancer is key," says Singh, co-director of the ovarian cancer early detection program at Northwestern Memorial Hospital.
Dr. Diana Zuckerman also admits to being thrilled when Gardasil was approved to vaccinate girls against HPV. Zuckerman, president of the National Research Center for Women & Families in Washington, D.C., says since then she has analyzed reams of research and attended more meetings concerning the vaccine than she can even describe.
And for her and other staff members at her organization, whose sole purpose is to provide unbiased analysis of current research, the initial excitement has turned into skepticism about the wonders of the vaccine.
"We started out quite enthusiastic about Gardasil for girls. We've become less enthusiastic because we think the manufacturer is not being forthcoming about how long it lasts," Zuckerman says. "And it's so expensive, the most expensive vaccine ever sold in this country, so you want to make sure it lasts."
HPV is the name for a group of viruses that cause cervical cancer and genital warts. There are more than 120 types of HPV and as many as 40 of them are spread through sexual contact, according to the National Research Center for Women & Families. Many of the approximately 6 million people who are infected with genital HPV each year in the United States have no symptoms and don't know they are infected and 90 percent of cases clear up on their own without treatment. Not all HPV causes cancer, but 99 percent of cervical cancer can be traced to infection with a strain of HPV.
Controversy over the vaccines
The controversy over the safety and effectiveness of the HPV vaccine has ramped up in recent months with the approval in the U.S. of a second anti-cancer vaccine, Cervarix, and with the Centers for Disease Control and Prevention's approval of Gardasil for boys as well as girls.
Now parents of tweens and teens are slogging through Internet research and discussions with doctors to decide whether or not to vaccinate their children. At the same time, many doctors are wading through the same onslaught of information for and against the vaccines.
Angie Brocato of Darien remembers her doctor bringing up the vaccine when she brought her daughter in for a checkup at age 12. She'd done some research on the vaccine and decided she wasn't ready to vaccinate her daughter without more information.
A year later, when she brought her daughter in for another checkup, the discussion again turned to the HPV vaccine. But this time it was her doctor who told Brocato that, based on what she had heard about the vaccine, she couldn't in good conscience recommend it.
"We had basically said we weren't going to, I still don't think we'll get it," Brocato remembers. "And she said that she wasn't comfortable with it either at this point."
Brocato, who has a 13-year-old daughter and an 11-year-old son, is just one of many parents who want to do the best thing to care for their children, but who aren't sure what the right answer is. However, many national organizations, such as the American Academy of Pediatrics and the Centers for Disease Control, say the decision is easy-the vaccines, both Cervarix and Gardasil, are not only safe but can effectively eliminate the virus that causes almost all cases of cervical cancer.
"This is a very clearly needed vaccine for adolescent girls, reducing their lifetime risk of cervical cancer and it is very important as a preventive measure for the health of all women," says Dr. Joseph Bocchini, chairperson of the AAP's committee on infectious diseases and chairman of the Department of Pediatrics at Louisiana State University Health Sciences Center in Shreveport. 
Who's actually recommending?
But some parents, and experts, think Gardasil has been so heavily marketed that a doctor's recommendation isn't enough to go on when considering the vaccine for their children. Because vaccines in the United States are created by companies whose goal is to make a profit, it's not always easy to determine objectively the value of a specific vaccine. 
"Parents have to remember that people are selling this product and, like any product that's being sold, people have a vested interest in selling their product and making money and that puts parents in a difficult spot when deciding," Zuckerman says. "There's a lot of hype-the ads would make you think your daughter will get cervical cancer unless she gets this vaccine. But cervical cancer is still a pretty rare cancer in this country and the vaccine is, at most, 70 percent effective and probably less over time."
How long does it last?
Part of the controversy with the HPV vaccines revolves around how long the vaccines actually provide immunity. Because both Gardasil and Cervarix have been around for less than 10 years, it's not known if the immunity from HPV lasts indefinitely or if it wanes over time. Glaxo, which manufactures Cervarix, has distributed more than 7 million doses of the vaccine in other countries and has tracked immunity for the 6.4 years since vaccinations started. While they will continue to track immunity, current research shows that immunity continues for at least that length of time, says Jeff McLaughlin, spokesperson at Glaxo.
Merck, the manufacturer of Gardasil, has also tracked the ongoing immunity provided by the vaccine. At this point Gardisal shows immunity for five years, and ongoing studies will continue, says Jennifer Allen Woodruff, spokesperson for Merck. In one study, a challenge dose was given to women five years after receiving the vaccine to check immune response. Woodruff says this dose is given to check if immune memory is evident at that point because studies can't expose women to the actual virus.
"We have seen what is called immune memory with Gardasil, and that's considered to be a hallmark of long-term value for the vaccine," Woodruff says. At this point there is no indication that a booster shot would be needed, she says.
Zuckerman says it's not quite that clear-cut. "We're particularly concerned about Gardasil, not Cervarix, because in the one study Merck did about girls and young women, they gave a challenge dose of the vaccine at 60 months and then they measured their antibodies a short time later," she says. "To us, that looks like a booster shot. ... At three years, it looks like some of the protection is wearing off. In contrast, Cervarix is working longer than six years."
But the AAP's Bocchini says it's not unusual for vaccine immunity to wane over time. "These are new vaccines, so the thing we don't know is how long the immune response will last to enable the vaccines to remain effective," he says. "We have data out to at least six years and the vaccines remain effective at least six years, but longer than that we don't know. We don't know whether immunity will be lifelong or will require a booster."
He says it's important to give the shot early, even if a booster might be needed later. "It's really important to still give this vaccine prior to the onset of sexual activity."
Safety concerns
How long the vaccine lasts isn't the only concern for parents.
Recent media reports about girls who contracted fatal or debilitating illnesses such as Guillain-Barre Syndrome after receiving the vaccine have created Internet storms as parents react to the possibility that the vaccine isn't completely safe. 
But many of the experts in favor of the vaccine point out that no studies have linked GBS to the vaccine, and the number of people contracting those illnesses are the same whether individuals are vaccinated or not.
"Since we give this vaccine to large numbers of patients, when an event occurs after vaccines, we have to determine if the vaccine caused it or if it occurred by chance," Bocchini says. "At this point, the events that have occurred have been at a frequency that is no greater than we would expect in the general population. Although we have to continue to monitor for safety issues, there is no safety issue that has come up to cause concern about either vaccine."
Singh also thinks cautionary stories in the media haven't stood up to investigation.
"When most of these stories are really followed down, they haven't clearly connected the vaccine to someone dying of something," she says, noting that no vaccine comes without risk, so the decision to vaccinate comes down to evaluating whether or not the benefits outweigh the risks. When it comes to preventing cancer, she says the benefits of either vaccine outweigh the possibility of any rare complications. 
Another part of the controversy, Singh says, involves the fact that these vaccines are for sexually transmitted diseases, and many parents of tweens aren't ready to tackle the issue of their children's sexuality. 
"The thing I find fascinating about this discussion, we give Hepatitis B (vaccines) to babies when they're born. You get Hep B from sex or needles. Nobody says, my baby's been vaccinated, that means he or she will run out and have sex because she had (the vaccine)," Singh says. But some parents don't want their children to be overly confident about their level of protection from the vaccine once they become sexually active.
Angie Brocato admits to thinking about future attitudes when deciding whether to vaccinate her daughter. "I didn't want her to have any kind of false security over so-called safe sex. I don't want these girls to think they've got this shot and they're not subject to gonorrhea or HIV, and this shot only takes care of a few strands of one particular disease."
Zuckerman, who agrees the vaccines appear to prevent about 70 percent of HPVs, also notes that 30 percent of the viruses are not covered. "At best, it's an imperfect vaccine."
Vaccinating boys
With the recent approval of Gardasil for boys, parents need to have even more discussions with their doctors. In October, the CDC approved Gardasil for "permissive use" in males. It stopped short of recommending it for boys, leaving the decision to parents and doctors. Gardasil provides protection for boys from HPV-related genital warts.
"If you vaccinate all girls and boys, yes, it'll cost twice as much, but ... if you think about, that's how the virus is passed around, you get herd immunity," Singh says. "And genital warts are a drag. If we can affect boys' protection, why not? Plus it gets rid of the stigma, of making it a girls' problem."
But the issue of how long the vaccine provides immunity is just as critical for boys, Zuckerman says, and it makes the decision to vaccinate even less clear-cut. "We don't think 12-year-old boys are at a big risk of genital warts. 
The risk gets a lot higher when they get older," she says. "We don't think most families are going to want to vaccinate their boys, at $400 a vaccine every few years, to protect against genital warts."
Making the decision
While some other states have mandated the vaccine, in Illinois the decision to vaccinate comes down to the parent's choice. Deciding whether to vaccinate using Gardasil or Cervarix also rests with parents and their doctors. 
While the AAP recommends children receive the vaccine at ages 11 or 12, Zuckerman says a wait-and-see approach regarding the vaccines won't hurt. 
"For those who are a little concerned and would like to know more before they vaccinate, it appears that delaying vaccination for a few years is not a really big problem, but a sexually active teen should get pap smears." All the experts agree that whether children are vaccinated or not, pap smears, once they become sexually active, remain a key element in preventing cervical cancer and shouldn't be overlooked in the fight against the disease.
Singh also recommends that parents who aren't getting the answers they need from their pediatrician regarding the vaccines should continue to ask the questions until they're comfortable with their decision. "Talk to your OB/GYN. Seek out other information," she says. "There's too much information out there in some ways, but people can try to direct you towards good vaccination information."

This article appeared in the January 2010 edition of Chicago Parent.