Posted tagged ‘Gardasil’

Support for HPV vaccination continues to grow

September 24, 2018

The Pediatric Insider

© 2018 Roy Benaroch, MD

Two new studies have added to the enormous weight of evidence in support of HPV vaccination.

From Pediatrics, September 2018, “Primary Ovarian Insufficiency and Adolescent Vaccination”. This study looked at almost 200,000 young women enrolled in the Kaiser health system from 2006 to 2014, looking at rates of ovarian failure in women who had received vaccines versus women who didn’t. The study was triggered by concerns about ovarian failure related to HPV vaccination – concerns that continue to swirl on Facebook and other social media sites. The study showed that HPV vaccine didn’t trigger ovarian failure, even after an exhaustive search allowing for an association at any time period after vaccination. It just isn’t there. And ovarian failure wasn’t caused by other teen vaccines, either.

And, from Pediatrics August 2018, “Legislation to Increase Uptake of HPV Vaccination and Adolescent Sexual Behaviors”. Another concern that’s been raised is whether encouraging HPV vaccination interferes with “safe sex” or abstinence messaging. By encouraging a vaccine to prevent a sexually transmitted infection, are we giving permission to our children to have sex? This study looked at that question through the lens of how the individual States have approached HPV vaccine legislation. Some states have passed specific laws to encourage HPV vaccines; others have not. It turns out that adolescent sex behaviors, including having sexual relationships and using condoms, isn’t affected by how strongly their states encourage HPV vaccines.


Neither of these specific studies is a slam-dunk – and that’s the way science can be. We accumulate more and more evidence as time goes by. But they add up to what we can say with confidence: HPV vaccines are safe, and HPV vaccines can help protect your children from cancer. It’s a compelling story, and something parents ought to feel good about. There is no reason to hesitate – make sure your children are protected and up to date.


Key studies on HPV vaccination

A huge, comprehensive review of studies from May, 2018 showed that “There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26.” (Earlier review here) This study from August 2018 documented dropping cancer rates after the vaccine was introduced. The vaccine is working, and it’s saving lives.

A 2010 review of post-licensure studies showing good safety profile, and another large study of 600,000 doses in 2011 didn’t find any important safety concerns. Another 2012 study found no significant problems after almost 200,000 doses. These are big, reassuring studies that all say the same thing: HPV vaccination is safe.

Studies showing HPV vaccines do not cause chronic fatigue, autoimmune diseases, complex regional pain syndrome or postural orthostatic tachycardia syndrome. These and other studies looking for specific diseases or conditions caused or worsened by HPV vaccines have all been reassuring – these vaccines aren’t associated with these or any other worrisome health conditions.

HPV vaccine for men: A definite maybe

October 19, 2010

The Pediatric Insider

© 2010 Roy Benaroch, MD

I updated this post here. Go read that first.

Beth wrote, “I plan on having my daughter vaccinated against HPV when she’s the right age (which is what by the way?). Recently, some friends were saying they were planning to have their sons receive the vaccine as well because although males obviously don’t get cervical cancer, they can spread HPV and put their future partners at risk. Is this true?”

Yes, men can catch HPV infections, and spread them to women. But that might not be reason enough to have your son vaccinated.

First, background: HPV (human papilloma virus) is by far the most common sexually-transmitted infection. About 50% of all men and women will be infected by at least one strain of HPV at least once in their lives; about 20 million Americans are infected (and infectious) right now, and 6 million new cases of HPV infection occur each year in the United States. There is a lot of virus going around.

HPV is the direct cause of genital warts. It also causes cervical cancer (12,000 new cases a year in the United States), vulvar and vaginal cancers (4,000 per year), as well as cancers of the anus, head, and neck in men and women. From a pediatric perspective, it can also cause warts in the airways of young babies exposed during childbirth, which can be lethal or very difficult to treat. However, most people infected with HPV do not develop any of these long term problems—the virus is cleared by the immune system.

Most cancers are caused by two specific strains of HPV, and those strains are included in both brands of HPV vaccine (Gardasil and Cervarix.) About 70-80% of cervical cancers could be prevented by widespread use of these vaccines. Gardasil also protects against  two other HPV strains that cause genital warts. Though Cervarix doesn’t include these two wart-causing types, there is some evidence for cross protection these and other strains from the vaccine.

Both HPV vaccines are very safe. Despite media scaremongering and a hysterical anti-vaccine movement eager to encourage the spread of disease, there have been very few serious reactions to these vaccines. The most common reaction is pain at the injection site (these vaccines do seem more painful than others). There have also been reports of fainting after HPV vaccine, which isn’t unexpected among teenagers after any injection or medical procedure.

So why wouldn’t you want to give these vaccines to boys?

  1. The diseases they prevent in men are quite rare, far rarer than cervical cancer. For instance, penile cancer affects about 1,000 men each year, compared to 16,000 women who get cancer of their reproductive organs. Though HPV can contribute to cancers of the head and neck in both men and women, smoking accounts for far more cases of these diseases.
  2. It’s difficult to prove that this vaccine actually works in men. The point of the vaccine is to 1. prevent HPV infection, which 2. prevents HPV from causing cancer. In women, early HPV infections can be demonstrated by pap smear—there is no similar way to show that men have caught HPV. Blood tests in both men and women can serve as “surrogate markers” of infection, but aren’t really accurate for specific patients to predict disease. Cancers develop rarely, even in infected people, and they may take years or decades to develop. Penis cancer is primarily a disease of elderly, uncircumcised men. Following boys for 50 years to see how many of them develop penis cancer is nearly impossible. So whether HPV vaccination prevents cancer in men will be difficult to prove. Not only that, but we can’t even be sure that vaccination prevents men from spreading HPV to their partners—again, it’s very difficult to know what men are even infected, so correlating new infections in their partners would be logistically impossible. That doesn’t mean that the vaccine doesn’t work, just that it’s hard to prove that it works to the same degree that we require proof of effectiveness of other vaccines.
  3. It’s very, very expensive. A three-dose course of HPV vaccine costs me about $400, plus administration and storage and other associated costs. Is that worth it?

There are some high risks groups of boys who ought to be more-strongly considered for HPV vaccinations. Men who have sex with men are at especially high risk for HPV-associated cancers, probably about 17 times the population risk. And men with immune-compromising disorders, like HIV infections, are at a very high risk both for cancers from HPV infections, but also for extensive warts that are more-difficult to treat.

A legitimate question: how would most parents know that their son might be engaging, or might later engage, in higher-risk sexual activities? Since you might not know, perhaps it would be best to vaccinate all boys. I can see both sides of that argument.

At this point I would confidently say that all girls ought to be vaccinated—both the safety and effectiveness have been well demonstrated. The FDA has approved HPV vaccines from age 9-26, and the AAP recommends girls begin the three dose series at age 11 or 12. All three doses (which are typically given over six months) need to be received prior to the first sexual encounter to work best. In my clinic, most of my patients have stable homes with good health insurance, so I think it’s reasonable to begin vaccinations a few years older than the AAP recommends, but if you’re not sure you’ll still have health insurance next year, start the vaccines when they’re covered.

Currently, the AAP and CDC take a “permissive” stance on HPV vaccines for boys, and I agree with that. It’s a vaccine that parents ought to consider, but because of the shortcomings discussed here, it’s not “recommended” for all boys. It may also not be covered by health insurance, so you might want to ask about that and the retail charge before your son is vaccinated.

More info:

Media scaremongering and Gardasil

August 27, 2009

The Pediatric Insider © 2009 Roy Benaroch, MD

Count on routine media outlets to mangle and misinterpret science news and information. The recent brouhaha over the Gardasil vaccine is a typical example of how science writers in big media are far more interested in making a splash than in conveying accurate, useful information.

On August 19, 2009, the Journal of the American Medical Association published “Postlicensure Safety Surveillance for Quadravelent Human Papillomavirus Recombinant Vaccine”, a study reviewing adverse events following administration of Gardasil. That’s Merck’s vaccine designed to prevent infections with the virus that causes genital warts and cervical cancer.

The article was pre-released 2 days early to news outlets, though not to physicians. As is typical, doctors don’t get to read these studies until after “the news” folds, spindles, and mutilates the story for a few days. By the time most physicians get to actually read the report, the news has moved on to some other crisis.

Some headlines, reflecting how the study was reported:

Using the resources of my crack research team (I asked the librarian at Children’s Healthcare of Atlanta to send me a copy of the article, and I read it this past weekend), I can now reveal what the JAMA article actually said. As always, you can depend on me for true Pediatric Insider information.

But first, some required boring background information: infections with Human Papilloma Virus (HPV) are the root cause of genital warts and cervical cancer. This is by far the most common sexually transmitted disease, with almost 80% of US adult women having been infected at some point in their lives. Though most infections with HPV are successfully cleared by the immune system, some infections remain active for a long time, and can eventually lead to serious problems. The virus can also more rarely cause throat and oral cancers, anal problems, and nodules in the respiratory tract of babies that lead to serious, even fatal, respiratory problems.

In 2006 the FDA approved a vaccine called “Gardasil” that had been shown to prevent infections by 4 of the nearly 100 strains of HPV. These four were among the most common strains to cause cancer and warts, and probably account for about 70% of cases of cervical cancer in women.

The study reviewed all side effects reported to the Vaccine Adverse Event Reporting System, a passive government database. Anyone can report side effects to this database, including representatives from Merck (they reported more of the side effects than anyone else), medical personnel, or patients. Any sort of side effect can be reported at any time—the database is meant to cast as wide a net as possible, to collect any possible side effects.

About 23 million doses of Gardasil had been administered during the 2 ½ years of the study period. During that time, 12, 424 adverse events were reported, meaning one in 1850 doses. The most common reactions were fainting (14%), dizziness (14%), nausea (9%), and headache (8%). Of the 12,424 adverse events, 772 were considered “serious”—including allergic reactions, blood clots, and neurologic manifestations. That’s one in about 30,000 doses.

Press reports about this study invariably focused on deaths. The most widely quoted number was 32 deaths reported in the study; of those, 8 were second-hand reports that couldn’t be verified, and 4 didn’t include identifying information. There were 20 verified deaths reported to VAERS for which medical records could be reviewed. The cause of death among these 20 were:

  • 4 – unexplained
  • 2 – complications of diabetes mellitus*
  • 1 – prescription drug overdose*
  • 1 – amyotrophic lateral sclerosis (Lou Gehrig’s Disease)*
  • 1- bacterial meningitis*
  • 1 – influenza*
  • 3 – pulmonary embolism; two of the cases were also taking contraceptive pills, a known risk factor for clotting. One of these was also a complication of diabetes mellitus (another cause of PE), but it’s unclear whether that person was also on contraceptives.*
  • 6 – cardiac causes including arrhythmias
  • 2 – seizures

(These total 21 because one reported case had 2 of these conditions.) I starred items that are clearly related to pre-existing or unrelated cases, though in some instances like the 2 with seizures, it’s not clear whether this was a preexisting problem or not. But liberally counting the ones that might have been caused by Gardasil, there were 12 deaths. Among 23 million doses. That’s one in about 2 million.

And it’s not at all clear that even these 12 deaths were in any way related to Gardasil. Though it seems heartless to say so, there are always some deaths among any group of people, even healthy young adults. I couldn’t find an exact expected death rate for women aged 9-26 (that’s the ages where Gardasil is licensed), but just for comparison I did find the death rate for teenagers 15-19—nationwide in the US, it’s 65 per 100,000 per four years. Assuming ~ 10 million different women got Gardasil over the 2 ½ year period of the study (each patient is supposed to get 3 doses, but most in fact get only 1 or 2), if the death rate of 9-26 year old women is the same as the death rate of 15-19 year old teens (or at least in that ballpark, which is reasonable to assume) then you’d expect (2 ½ * 65 * 10,000,000)/(100 000*4) deaths during the study period, or 4065 deaths. Even if you assume about ½ of these were from car accidents, homicide, and suicide (these are the leading causes of death at that age, though violent death is more common in males), that would still mean you’d expect about 2,000 deaths to be reported.

2,000 deaths expected. But only 32 were reported. This is good news, right? From a statistical point of view, the reported deaths were very much within the rate of deaths that’s expected—in fact, it was far, far lower.

Now, there are some reasonable criticisms of the study. It’s entirely possible that some deaths went unreported—this is a passive system, and someone has to take the time to report deaths. However, after such a dramatic and serious event as a death you’d think at least most families and physicians would make a report. But let’s even assume that only 1 in ten deaths was reported—even then, if there really were 320 deaths rather than 32, that’s still far less than the expected ballpark “background” death rate of 2,000.

Though press reports concentrated on the reported deaths, when you look at the study and the actual numbers the only reasonable conclusion is that there is no increased risk of death after vaccination with Gardasil. Oddly, few of the mass-media outlets reported the study that way.

Of the 772 reported serious reactions, many were self-limited, and many, like the deaths, were clearly not related to vaccination. Clearly, however, this are some true side effects; like any medical intervention, Gardasil has both risks and benefits. But it’s good to know that serious reactions are so rare.

Of the adverse events that did occur at relatively high rates, fainting is one that we ought to be watching out for. If a girl faints after a dose of vaccine, she can fall and hit her head or otherwise injure herself—in fact, that was the most common of the 772 “serious” side effects, an injury after a fall following fainting. For this reason, Gardasil should be administered while the patient is lying down, and afterwards it’s a good idea to stay lying down for about 5 minutes. Note that teenagers, male and female, are apt to faint after other vaccines, blood draws, and other medical procedures, so lying down after any sort of shot is probably a good idea.

There are some important questions about Gardasil that still need answers. It’s unclear how long protection will last, and it’s unclear how Gardasil immunization will effect rates of cervical cancer many years later—those studies just haven’t been done yet, because they take so much time. Reasonable families, given these unknowns, may have misgivings about immunizing now against a disease that shows up so much later. Gardasil vaccination is also very, very expensive—at least $400 for the three doses, and considering that cervical cancer is not common, and can be screened for with pap smears, there may be better uses for these health care dollars. Still, from a safety point of view, the recently published study is very reassuring, and very good news for families considering this vaccine. Too bad many in the press didn’t bother to get their facts straight to present the study in a truthful manner.