Our first 10 Things You Might Not Know About Gardasil generated quite a response. It's a few months later and we're still getting comments and emails, and finding discussions about what we wrote on other blogs and websites. We're happy that we've helped to get people thinking and talking about this issue, and we can see that it isn't going away anytime soon. So we've continued following the press coverage and doing our own research, and we're back with 10 More Things You Might Not Know About Gardasil.
1. There is a controversy surrounding Gardasil in
This story has gotten a lot of press coverage so we’re not going to rehash all of the details here, but here’s a quick timeline of what happened:
~In early February, Texas Governor Rick Perry issued an executive order making Gardasil mandatory for girls entering the sixth grade. In doing so, he bypassed the state legislature and a public outcry of opposition.
~After the order was issued, it came out that Governor Perry has some ties to Merck that some people found questionable. His former chief of staff is one of Merck’s lobbyists in
~The situation in
~On March 14th, the Texas House of Representatives voted to overturn Governor Perry’s executive order. The bill would keep Gardasil off of the list of required vaccines for students. A similar bill is being considered by the state Senate. The issue is not just the opposition to Gardasil, but also the fact that the governor bypassed the legislature and may have overstepped his authority by issuing a binding executive order. If the bill is passed, it could still be vetoed by the governor, so lawmakers are trying to get the bill to the governor’s desk as quickly as possible so that they will have time to override a potential veto before the legislative session ends in May.
~In late April, a revised version of the bill passed both the Texas House and Senate and was sent to the governor, who then had 10 days to either sign or veto it. The legislature has enough votes to override a veto. The bill prevents state officials from requiring the vaccine for school admittance, but the ban will expire after four years so that the vaccine can be reevaluated.
~On May 8th, Governor Perry announced that he would not veto the bill. He was extremely critical of the bill and the legislature, but said that a veto would be pointless since there were enough votes to override it.
In contrast to the Texas drama, New Hampshire has largely avoided controversy by choosing not to make Gardasil mandatory, but instead to make it available free of charge to girls ages 11 to 18 through a state program for immunization of minors. One of the stated reasons for making a vaccine (especially a very expensive one like Gardasil) mandatory is that it levels the playing field, allowing people at all income levels to have the same access to the treatment. The New Hampshire approach isn't perfect either--there are waiting lists and some reports of doctors running out of the vaccine and having to wait for more--but it does provide equal access while also allowing parents more freedom to decide if and when their children should be vaccinated.
2. A variety of adverse reactions to Gardasil have been reported.
Merck has released a list of the side effects that someone could experience from Gardasil: pain, swelling, itching and redness at the injection site, fever, nausea, and dizziness.
However, the list of adverse reactions from the first dose of Gardasil that has been reported so far is more extensive. It includes:
- loss of consciousness and syncope
- dizziness, shakiness,"feeling faint"
- loss of vision, decrease in quality of vision, dryness of eyes
- abnormal speech
- nausea, vomiting
- pallor, purple coloration of the lips
- fever, chills
- dyskinesia (difficulty or distortion in performing voluntary movements)
- hypokinesia (slow or diminished movement of the body musculature)
- difficulty swallowing
- joint pain
- Guillain-Barre Syndrome (an immune disorder which effects the peripheral nervous system and in extreme cases can cause paralysis)
- hives, itching, rashes, blisters, vesicles, and skin ulcers
- swelling of the arms, swelling of the lower extremities, swelling of the lymph nodes
- severe pain at the site of injection.
One of the interesting things about this information is that quite a few of the negative reactions that were reported, including most of the cases of Guillain-Barre Syndrome, occurred in patients that had received another vaccine at the same time as Gardasil. (The meningococcal vaccine Menactra, which appears in several of the Gardasil reports, has been previously associated with Guillain-Barre warnings) As we mentioned in our first Ten Things, Gardasil was only tested for safety when administered at the same time as the Hepatitis B vaccine. No other combinations of vaccines were tested, so it is difficult to say if some of these negative reactions were caused by Gardasil, by the other vaccine involved, by the combination of the two vaccines, or by some other factors.
3. Anyone who is allergic to the ingredients of Gardasil should not receive the vaccine.
Gardasil is fermented in giant vats of yeast paste, which means that anyone with a yeast allergy should not get the vaccine. The CDC’s Vaccine Information Statement lists yeast allergy as a reason to avoid the vaccine, but the Patient Product Information on gardasil.com does not specifically mention yeast.
The listed ingredients are: “purified inactive proteins that come from HPV Types 6, 11, 16, and 18…amorphous aluminum hydroxyphosphate sulfate, sodium chloride, L-histidine, polysorbate 80, sodium borate, and water for injection.”
If you or your child have ever had even a mild negative reaction to a vaccine, or you have any allergies at all, even ones that you may not think could possibly be relevant, you should talk to your doctor and make sure you're aware of any potential complications. (Merck also recommends that you tell your doctor if you or your child have any type of bleeding disorder that would make injections difficult, a weakened immune system, a fever or other mild illness, or are taking any prescription or over-the-counter medications.)
Maybe in some circles it's common knowledge that yeast is sometimes used to develop vaccines, but we didn't know it and many of our friends didn't either. You may have a condition like a yeast allergy and not be aware of it, or your doctor may not be aware of it, and it could cause a negative reaction that you never even knew you should be looking out for. So seek out as much information as you can and talk everything through with your doctor until you feel comfortable. It's your health, so be as cautious as you want to be.
4. Women who may be pregnant, women who are breast-feeding, and women who have already been exposed to HPV should approach Gardasil with caution.
Women who may be pregnant and women who are breast-feeding should be cautious, because there are some questions about whether Gardasil could potentially affect fertility or cause harm to a fetus or a nursing infant. Full information about the testing that was conducted on pregnant and breast-feeding women can be found on the FDA's website, but we have pulled out some of the relevant quotes.
“…it is not known whether GARDASIL can cause fetal harm when administered to a pregnant woman or if it can affect reproductive capacity. GARDASIL should be given to a pregnant woman only if clearly needed.”
“The effect of GARDASIL on male fertility has not been studied.”
“Overall, the proportions of pregnancies with an adverse outcome were comparable in subjects who received GARDASIL and subjects who received placebo.” (One note here—both Gardasil and the placebo contained aluminum, so if you are concerned about the potential harmful effects of aluminum, it’s not possible to tell whether aluminum could have been a factor in any of the complications that were experienced).
“It is not known whether vaccine antigens or antibodies induced by the vaccine are excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when GARDASIL is administered to a nursing woman.”
Also, a small number of women who used the vaccine near the time of conception gave birth to children suffering from birth defects, although there is no specific evidence that Gardasil was the cause.
Merck claims that Gardasil may still be beneficial for women who have already been exposed to HPV, since the vaccine protects against four HPV strains and it is unlikely that a woman would be exposed to all four, so the vaccine could still provide protection against the remaining strains. But it is worth noting that after reviewing the clinical trials of Gardasil last summer, the FDA did raise a concern about the potential for the vaccine to lead to "an increased number of cases of a cancer precursor" among patients already infected with one of the strains of HPV affected by Gardasil. It's important to remember that most cases of HPV show no symptoms at all and that the virus can remain in your body for months or even years.
So if you're considering Gardasil but think there's a chance you may have HPV, you may want to consider your HPV testing options before you go ahead with the vaccine.
5. A new study published by JAMA shows that only about 3.4% of women have one of the four strains of HPV that Gardasil protects against.
A study published in the February 28th issue of the Journal of the American Medical Association has found that about 26% of women aged 14 to 59 in the
With all of the statistics being thrown around in the media about how common HPV is and how many millions of people will get it in their lifetimes, that perspective is important. There are dozens of strains of HPV. A few of them are linked to genital warts and a few of them are linked to cervical cancer. The majority of cases of HPV will eventually clear on their own. Getting HPV does not mean you will get cancer. Gardasil protects against four specific strains of HPV. Getting vaccinated with Gardasil does not mean that you’ll never get HPV, or that you’ll never be at risk for genital warts or cervical cancer. Your risk will be greatly reduced, but not eliminated.
6. Questions have been raised about several of the ingredients in Gardasil.
Gardasil is made with genetically engineered materials. Being genetically engineered doesn't automatically make Gardasil evil and harmful, but it's interesting that while many people say that the idea of genetically engineered food seems unnatural and makes them uncomfortable, a lot of those same people are putting a genetically engineered vaccine into their (or their children's) bodies without a second thought. Products made with genetically modified organisms are still controversial, and many people feel that such products should be studied more thoroughly, labeled more clearly, or even banned altogether, while others believe that they are safe and that the potential benefits of genetically engineered products outweigh the potential risks. [Nutrition Action HealthLetter] [ScienceDaily] [Greenpeace] [BBC News]
Polysorbate-80, another Gardasil ingredient, has also been linked to possible negative effects. There are some claims that polysorbate is potentially carcinogenic, and polysorbate-80 has also been linked to infertility in mice, although the amount of polysorbate in the three doses of Gardasil is thought to be too low to cause harm in humans.
Sodium borate is the main ingredient in boric acid. (Powdered boric acid is often used to kill cockroaches.)
Sodium borate poisoning can be acute or chronic. Acute, accidental sodium borate poisoning usually occurs when someone swallows powdered roach-killing products that contain the chemical.
Poisoning may also occur in those who are repeatedly exposed to sodium borate. In the past, boric acid was used to disinfect and treat wounds. Patients who received such treatment over and over again got sick, and some died. Because boric acid is now known to be a dangerous poison, it is no longer commonly used in medical preparations. However, boric acid is contained in some vaginal suppositories used for yeast infections, although this is NOT a standard treatment.
Some of the symptoms listed for sodium borate poisoning are similar to those that have been reported by patients who have suffered negative effects from Gardasil.
7. A researcher who participated in studies of Gardasil has expressed her concerns about making the vaccine mandatory.
Researcher blasts HPV marketing BY CINDY BEVINGTON Wednesday, March 14, 2007
LEBANON, N.H. - A lead researcher who spent 20 years developing the vaccine for humanpapilloma virus says the HPV vaccine is not for younger girls, and that it is "silly" for states to be mandating it for them.
Not only that, she says it's not been tested for effectiveness in younger girls, and administering the vaccine to girls as young as 9 may not even protect them at all. And, in the worst-case scenario, instead of serving to reduce the numbers of cervical cancers within 25 years, such a vaccination crusade actually could cause the numbers to go up.
"Giving it to 11-year-olds is a great big public health experiment," said Diane M. Harper, who is a scientist, physician, professor and the director of the Gynecologic Cancer Prevention Research Group at the Norris Cotton Cancer Center at Dartmouth Medical School in New Hampshire. "It is silly to mandate vaccination of 11- to 12-year-old girls There also is not enough evidence gathered on side effects to know that safety is not an issue."
Internationally recognized as a pioneer in the field, Harper has been studying HPV and a possible vaccine for several of the more than 100 strains of HPV for 20 years - most of her adult life. All of her trials have been with subjects ages 15 to 25. In her own practice, Harper believes the ideal way of administering the new vaccine is to offer it to women ages 18 and up. At the time of their first inoculation, they should be tested for the presence of HPV in their system. If the test comes back negative, then schedule the follow-up series of the three-part shots. But if it comes back positive? "Then we don't know squat, because medically we don't know how to respond to that," Harper said.
Harper is an independent researcher whose vaccine work is funded through Dartmouth in part by both Merck & Co. and GlaxoSmithKline, which means she is an employee of the university, not the drug companies. Merck's vaccine, Gardasil, protects against four strains of HPV, two of which cause genital warts, Nos. 6 and 11. The other two, HPV 16 and 18, are cancer-causing viruses.
Merck's vaccine was approved last year by the Food and Drug Administration, and recommended in June for females ages 9 to 26 by the Centers for Disease Control's Advisory Committee on Immunization Practices (ACIP). Glaxo has stated publicly that its vaccine, Cervarix, which protects against the two cancer-causing strains, should be on the market by 2008.
As the director of an international clinical trial for these vaccines, and as author of lead articles about the vaccines' effectiveness, Harper has been quoted widely as saying this vaccine could have enormous potential to eradicate the great majority of cervical cancers. Picking up on this, but before the trials were even completed, major news media and women's advocacy groups began trumpeting the vaccine as an answer to cancer of the cervix.
Once it was approved by the FDA and ACIP, Women In Government (WIG), a non-profit organization comprised of female state and federal legislators, began championing Merck's vaccine in their home states, with many of the ladies introducing legislation that would mandate the vaccine for 11- and 12-year-olds. In Indiana, Sen. Connie Lawson, R-Danville, introduced such a bill in this year's General Assembly, but in the face of strong opposition, it was reduced to an education/information-only bill that requires data collection on any Hoosier girls who do get the vaccine. The bill is now awaiting a hearing in the Indiana House. So far at least 26 states are reported to be considering some form of legislation requiring the new vaccine for younger girls. In February, Republican Texas Gov. Rick Perry bypassed his legislature and mandated it for all 11- and 12-year-old girls in his state. Monday, The Associated Press reported that New Mexico's governor, Democratic presidential contender Bill Richardson, is set to sign a bill requiring sixth grade girls in his state to get the vaccine.
The idea is to inoculate them before they become sexually active, since HPV can be spread through sexual intercourse. But that idea, no matter how good the intentions behind it, is not the right thinking, Harper said. The zealousness to inoculate all these younger girls may very well backfire at the very time they need protection most, she said.
"This vaccine should not be mandated for 11-year-old girls," she reiterated. "It's not been tested in little girls for efficacy. At 11, these girls don't get cervical cancer - they won't know for 25 years if they will get cervical cancer.
"Also, the public needs to know that with vaccinated women and women who still get Pap smears (which test for abnormal cells that can lead to cancer), some of them will still get cervical cancer."
The reason, she said, is because the vaccine does not protect against all HPV viruses that cause cancer - it's only effective against two that cause about 70 percent of cervical cancers.
For months, Harper said, she's been trying to convince major television and print media to listen to her and tell the facts about the usefulness and effectiveness of this vaccine. "But no one will print it," she said.
According to Harper, the facts about the HPV vaccine are:
- It is not a cancer vaccine or cure. It is a prophylactic - preventative -vaccine for a virus that can cause cancer. "Merck has proven it has zero percent effectiveness for curing cancer," Harper said. "But it is a very, very good vaccine that prevents types of HPV responsible for half of the high-grade cervical lesions that cause about 70 percent of cervical cancers. For the U.S. what that means is the vaccine will prevent about half of high-grade precursors of cancer but half will still occur, so hundreds of thousands of women who are vaccinated with Gardasil and get yearly Pap testing will still get a high-grade dysplasia (cell abnormality)."
- It is not 100 percent effective against all HPVs. It is 100 percent effective against two types that cause 70 percent of cervical cancers.
- The vaccine only works if the woman/girl does not have a current vaccine type related infection (in other words, the vaccine only works when the woman/girl does not have HPV 6, 11, 16 or 18 - the viruses that Gardasil targets when she receives her first vaccine shot).
- The vaccine doesn't care if the girl/woman has been sexually active, Harper said. "HPV is a skin-to-skin infection. Although the only way to get cervical dysplasia is through an HPV infection, and HPV is most often associated with sexual activity, HPV is not just spread through sex. We have multiple papers where that's documented. We know that 3-year-olds, 5-year-olds, 10-year-olds, and women who have never had sex have been found to be positive for the cancer-causing HPV types."
- Therefore, for example, if a girl is positive for HPV 16 when she is inoculated with the vaccine at any age, she will not be protected against it later, Harper said. "That means it's a failure and those people are at risk for getting the HPV 16 and 18 cancers later."
- The only way to test for the presence of HPV is through a vaginal swab -which is inappropriate for young girls, she said.
- So what happens if the girls are vaccinated anyway, not knowing whether they were carrying the virus at the time of their inoculation? "They will not be protected if they were positive for the virus at the time they are vaccinated," Harper said.
- That is why it is important to note that the vaccine has not been tested for efficacy (effectiveness) in younger girls, she said. Instead, the effectiveness was "bridged" from the older girls to the younger ones -meaning that Merck assumed that because it proved effective in the older girls, it also would be effective in the younger ones. The actual tests on the younger girls, ages 9 to 15, were only for safety and immune response, Harper said, and then only as a shot by itself, or in combination with only one other vaccine, Hepatitis B. It has not been tested in conjunction with any other shots a girl receives at about age 11, Harper said.
- So far more than 40 cases of Guillain-Barre syndrome - a dangerous immune disorder that causes tingling, numbness and even paralysis of the muscles have been reported in girls who have received the HPV vaccine in combination with the meningitis vaccine. Scientists already know that sometimes a vaccine can trigger the syndrome in a subject. "With the HPV vaccine, it is a small number but higher than is expected, and we don't know if it's the combination of the two, or the meningitis alone," Harper said.
- In the end, inoculating young girls may backfire because it will give them a false sense of protection. And, for both young girls and women, because the vaccine's purpose has been so misinterpreted - and mis-marketed - Harper feels that too many girls and women who have had the vaccine will develop a false sense of security, believing they are immune to cancer when they are not, and failing to continue with their annual Pap exams, are crucial to diagnosing dysplasia before it can develop into cancer.
The message to consumers, Harper said, is don't stop getting Pap smears just because you've gotten the HPV vaccine. "This vaccine is good, and it will save a huge number of lives around the world," Harper said. "But an important point is that, if women get the vaccine and then not get their Pap smears, or decide to get them infrequently, what will happen in the U.S. is that we will have an increase in cervical cancer, because the Pap screening does a very good job.
"That's my main diatribe. We don't need mandatory vaccinations for little girls. What we do need to ask, though, is how long does it last, and when do you need a booster?"
For the governors of the states in this country, Harper has another message. One has to do with the fact that vaccinating little girls now is not going to protect them later. Since it can take a decade or more to even manifest itself as dysplasia, the HPVs against which this vaccine works may infect a little girl at the age she needs the vaccine most - meaning she will have to have a booster at the right point in time or she will not be protected. And, remember, it won't work at all if she was positive for the virus when she was inoculated in the first place.
Merck knows this, Harper said. "To mandate now is simply to Merck's benefit, and only to Merck's benefit," she said. Merck was required to put together a database on the efficacy in children before Gardasil was approved, Harper said. But instead, the company put together four study sites that "are not necessarily representative, and may not even have enough numbers to determine what they need to know."
Since she doesn't personally have access to the money Merck and GlaxoSmithKline pay for her HPV vaccine research, Harper doesn't know exactly how much either has paid Dartmouth for her work. The trials are expensive, between $4,000 and $5,000 for each patient, she said. With over 100 patients in her study, some big bucks could be in the balance, should Merck or Glaxo become upset with her for making these comments.
Why, then, would she risk speaking out like this - at a time when her words very well could influence legislation across the country, and prompt legislators to drop the mandates? Isn't she afraid of losing her funding?
"I want to be able to sleep with myself when I go to bed at night," Harper said. "My concern is still, let's get women's health better. It is still a good vaccine. But let's be honest. Don't over-promise."
8. Men are increasingly seeking out information about HPV and Gardasil, especially in the gay community.In our first 10 Things we wrote about the fact that Gardasil was initially approved only for women (in the U.S.), and that most of the initial testing focused on women and girls and was only expanded later to begin to include more boys and men. We found this a little concerning considering that men can get and give HPV just like women can, and men can also (to a lesser degree than women) be at risk for genital warts and certain types of cancer as a result of HPV infection.
One of the biggest problems is the fact that there is no FDA-approved HPV test for men (and the CDC claims that such a test is unnecessary, which we ranted on in our first top ten), and there have been fewer studies done on HPV in men than there have been with women. So even if a man wanted to be as responsible as possible about STD testing, his options are limited where HPV is concerned. Many men probably don't even realize that even though they are getting tested for other STDs regularly, they are still at risk for HPV and may be putting their partners at risk as well.
Some research being done now has shown that HPV may be more prevalent in men than in women, and little is known about whether transmission rates differ from men to women, women to men, men to other men, etc. This information could be critical in determining who really should be getting the vaccine, what the cost benefits are, and what the best methods of preventing HPV infection are in general.
HPV is of particular concern to gay men, because rates of anal cancer have been rising.
While rates of anal cancer are low in the general population -- and more women than men get anal cancer every year -- they're disproportionately high among gay men and people who are HIV-positive or have other immune-suppressive conditions. Part of the explanation for increased cases of anal cancer is better reporting of the disease, but Bay Area doctors say it also could be tied to HIV rates.
Studies have shown rates of anal cancer as high as 35 cases for every 100,000 people among gay men -- a figure comparable to rates of cervical cancer in women before Pap tests were introduced as a screening tool 60 years ago. Since then, rates of cervical cancer have fallen 70 percent.
Some doctors are recommending anal Pap tests for gay men as a way of catching precancerous lesions before they become anal cancer, similar to the screening process for cervical cancer. And a growing number of men are choosing to go ahead and be vaccinated with Gardasil now as a way to potentially protect themselves and their partners from any strains of HPV that they have not already been exposed to. This is an "off license" use for Gardasil since the FDA has yet to approve it for adult men, but many men and some doctors feel that the potential benefits make it worthwhile.
We don't understand why Merck hasn't incorporated this angle into their marketing campaigns. We can't think of anything that would get the conservative abstinence-only crowd on board with mandatory vaccination faster than saying ''hey, guess what? the two groups of people who benefit most from our vaccine are your precious young daughters and...gay men!'' This must have simply been an oversight that we're sure Merck is working to remedy. Expect the PSA featuring Hilary Duff and Lance Bass any day now.
9. There is a product called carrageenan that may be effective at preventing HPV infection.
Some early research has shown that carrageenan, a thickening agent derived from algae, is a powerful HPV inhibitor.
In laboratory tests, carrageenan, a compound derived from red algae, prevented HPV infection by both genital wart and cancer-causing types. "We were floored by how much better it worked than anything else we have tested. It's effective at 100-fold lower concentration than the next best inhibitor we've found," said Dr. John Schiller, senior investigator at the National Cancer Institute.
Normally, HPV attacks cells by attaching to proteins on their surface and then chemically manipulating access to the cells. Carrageenan thwarts this process by attaching to HPV and preventing its entry into cells. [Medical News Today][CBS News]
Carrageenan has also been studied for its ability to prevent herpes and HIV transmission, but it was found to be much more powerful at inhibiting HPV transmission. Carrageenan is used in a variety of commercial products, including some sexual lubricants and lubricated condoms.
10. There is another HPV vaccine in development, which works differently than Gardasil.
GlaxoSmithKline is currently in the final stages of testing its own HPV vaccine, called Cervarix, which could be on the market as early as the end of the year. Like Gardasil, Cervarix protects against HPV types 16 and 18, which are said to cause most cases of cervical cancer. Unlike Gardasil, Cervarix does not protect against the types of HPV that cause most cases of genital warts.
Based on the information that has been released so far and the testing that is currently being done, it seems that Glaxo will try to market Cervarix as being better than Gardasil for two reasons. First, it may also protect against HPV types 45 and 31, which have also been linked to cervical cancer. Tests are underway now to determine whether this is definitely the case. And second, because Glaxo is using a special type of adjuvant that is different from the basic aluminum adjuvant used in Gardasil, they are claiming that Cervarix will provide better and longer-lasting immunity to HPV than Gardasil does, especially among girls aged 10-14.
Cervarix has also been tested on women as old as 55, which seems to indicate that Glaxo will target a wider market of women than Merck has with Gardasil. Earlier this year, Glaxo launched a study designed to directly compare the effectiveness of Cervarix and Gardasil and it will be interesting to see what the results are. Cervarix was also just recently approved for women ages 10-45 in Australia. We’ll keep researching and writing about Cervarix as it gets closer to approval in the U.S.~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Our conclusion now is still the same as it was when we wrote our first 10 Things. This is a complicated issue but it also comes down to a personal choice, and everyone should be able to make that choice for themselves or for their children with as much research and information and as little guilt and manipulation as possible.