Will She Shut Up About Gardasil, Already?

Hey, readers!  Do I still have any readers?  I’ve been MIA for a minute, sorry about that. It’s been kind of a crazy year what with my mom having breast cancer and then we had a little storm down here a few months ago.  You might have heard mention of it.  Anywho, a couple of months ago I wrote a piece for my local medical society’s magazine.  It’s intended for my adult medicine colleagues to give them a primer on the HPV vaccine, Gardasil.  I’ve written about it on here before, but I wanted to throw this piece in particular up on my blog because I feel it’s a nice summary of the vaccine.  It also contains some new information about the ACIP’s updated administration guidelines and the ideal timing of the vaccine.  I also happen to know that some of my adult doctor pals follow my blog but may not be local to me, so they wouldn’t have seen the magazine article.  Thanks for reading, hope this is useful!

Cheers!

Doctor Kate

Greetings, adult medicine colleagues! (If you are down here in the trenches of pediatric primary care with me, in flu season no less, I’m not going to tell you anything here that you don’t already know, but feel free to pass this on to a friend or two!)

I’m Kate and I’m a pediatrician.  Today, I’m asking you to take a minute and let me give you some facts about the HPV vaccine.  I am not going to discuss the details of the virus itself or the devastating effects it can have on humans.  I’m going to leave that discussion to my more qualified gynecologist and infectious disease specialist colleagues.  But as a pediatrician in primary care, I know a thing or two about vaccines.  You may not practice in an area that has anything to do with this vaccine, but most of you have children, possibly grandchildren.  You all have friends and family members with children.  Your nurses have children and they are talking to their friends and on social media about this vaccine.  I beg you to read my article for this reason – the lay public is hearing frightening things about this vaccine.  In some instances, they are hearing these frightening things from health care professionals.  The myths they encounter on the internet, on the news, and in their Sunday school classes are all completely unfounded.  You probably know that already.  However, research is showing us that the numbers of adolescents receiving the HPV vaccine are far too low.  Even more disappointing is the research showing that parents’ primary reason for not vaccinating their children is that we as physicians are failing to recommend it.  So, at your next family barbecue when your cousin Cheryl asks you what you think about getting the vaccine for her kids, I want you to be armed with facts and tell her you think it’s a great idea.  Because it’s a great idea!  Please, read on.

How effective is the HPV vaccine?

The short answer – the HPV vaccine is highly effective and has been enormously successful since being added to the ACIP (CDC’s advisory committee on immunization practices) recommended schedule in 2007.[i]  The longer answer – let’s look at some data.  According to one study published in The Journal of Infectious Disease in 2013, the quadrivalent HPV vaccine reduced carriage of the covered strains of human papilloma virus in over half of early adolescent females in the US, despite the fact that less than 40% of girls had been vaccinated.[ii]  The same study demonstrated 88% efficacy in vaccinated individuals.  That was just four years after the vaccine went into widespread use.  Not only is the vaccine highly effective in vaccinated individuals (better than the Mumps vaccine, actually), we are already starting to see herd immunity at work after just 4 years of use.  I’d say that’s pretty impressive.  Another more recent study published in Pediatrics in December of 2017 reaffirms the effectiveness of the HPV vaccine in both girls and boys.[iii]

Another nice feature of the HPV vaccine is its longevity.  Since the first Gardasil product was licensed in 2006, we have 12 years of data to go on.  So far, we have seen zero waning immunity.  The original recipients of the vaccine have immunoglobulin titers comparable to those recorded just after they were vaccinated.[iv] [v]  One concern I often hear about the HPV vaccine is that it is given too early to last a vaccinated individual through their most at-risk years, but the evidence demonstrates that this is not a concern.  I’ll be commenting more about the ideal timing of the vaccine later, stay tuned.

Is the vaccine safe?

It is!  The safety profile of the HPV vaccine is better than many of the other vaccines that we give to much younger children.  Common side effects are similar to those of other vaccines – pain and swelling at the injection site, fever, and malaise.  All are self-limiting and last 1-3 days with no long-term sequelae.  Incidence of serious side effects such as severe allergic reaction are comparable to most other vaccines – about one in one million recipients.[vi]  Rigorous safety trials have found no association with other serious side effects (see further down, I’ll prove it to you).

There is one common side effect of the HPV vaccine that is unique to this particular shot – 1 in 10 recipients will experience near syncope.  Why, you ask?  Well, I don’t have any studies to back me up here but I’ll give you my opinion.  Gardasil hurts.  I have personally received the three-dose series of the quadrivalent HPV vaccine back in my early twenties and I can tell you from personal experience that this shot hurts a lot.  A lot.  I have also vaginally delivered a full-term infant without anesthesia.  I have experienced the joy that is a 45-pound toddler head butting me in the nose.  I have stepped on a Lego with bare feet.  I can tell you that the HPV shot was the 2nd most painful experience of my life.  You can guess what the first was.  Combine a sudden, very painful stimulus with an adolescent flare for drama and you get some fainters.  In my clinical experience, they recover within about five minutes, you give them a little juice and some TLC and they walk out of the office unscathed.  It’s a small price to pay in exchange for the elimination of a common type of cancer.

If the vaccine is so safe, why all the frightening stories about serious side effects and reactions?

In spite of its great success, the HPV vaccine has suffered greatly from post hoc ergo propter hoc fallacy in the minds of the lay public (and even a number of appropriately concerned health professionals).  On the internet (and in some case reports) you can find countless stories of adolescents who have developed premature ovarian failure, autoimmune disease, dysautonomia (a.k.a. postural orthostatic tachycardia syndrome), seizure disorders, multiple sclerosis, and other demyelinating disorders after receiving the HPV vaccine.  The trouble is that these disorders tend to occur in early adolescence anyway.  Thus, we must rely on rigorous scientific study methods to tell us if these coincidences have any causal relationship or not.  Thus, I give you a short list of references for further reading if you are so inclined.  There are numerous others, but these are some of the higher quality ones.  The bottom line is this – there is no association between the HPV vaccine and any serious disease.  Concerns about potential connections have been thoroughly studied.  You can feel confident reassuring your patients, friends, and family members about the safety of the HPV vaccine.

  • Large, cohort study with over 60,000 subjects in each group – Willame C et al, “Risk of new onset autoimmune disease in 9- to 25-year-old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom”. Human Vaccine and Immunotherapeutics. Volume 12, 2016 –
  • Summary article covering all studies reviewed by the ACIP when making their most recent recommendations regarding HPV vaccine – Marokowitz LE et al, “Human Papillomavirus Vaccination: Recommendations of the Advisory Committee on Immunization Practices (ACIP)”. MMWR. August 29, 2014 / 63(RR05);1-30
  • Very large cohort study conducted in Sweden – Arnheim-Dahlström L et al, “Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study”. BMJ.  2013;347:f5906
  • A medium sized case control study conducted in French adolescent females – Grimaldi-Bensouda L et al, “Autoimmune disorders and quadrivalent human papillomavirus vaccination of young female subjects”. Journal of Internal Medicine. 2014 Apr;275(4):398-408
  • A medium sized surveillance study conducted in California – Chao C et al, “Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine”. J Intern Med. 2012 Feb;271(2):193-203
  • Safety study in South African women, all HIV positive (I.e. already immunocompromised), randomized placebo controlled study – Denny L et al, “Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: a partially-blind randomised placebo-controlled study”. Vaccine. 2013 Nov 19;31(48):5745-53
  • Long term randomized controlled study looking at both safety and immunogenicity – Schwartz TF et al, “Long-term immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in 10- to 14-year-old girls: open 6-year follow-up of an initial observer-blinded, randomized trial”. Pediatr Infect Dis J. 2014 Dec;33(12):1255-61
  • Klein NP et al. “Safety of quadrivalent human papillomavirus vaccine administered routinely to females”. Arch Pediatr Adolesc Med. 2012 Dec;166(12):1140-
  • Red Wine and Applesauce (blog) – http://www.redwineandapplesauce.com/2015/01/06/hpv-vaccine-and-multiple-sclerosis-reassuring-findings-about-gardasil-safety/– this post was written by Tara Haelle, a medical journalist who works for Forbes, this is her mommy blog – she writes a nice review article but has links to the source papers she references if you want to look at those as well
  • Red Wine and Applesauce (blog) – http://www.redwineandapplesauce.com/2014/07/08/nope-the-hpv-vaccine-doesnt-cause-blood-clots/– This is Tara’s review article of the literature looking at a connection with blood clots
  • Moms Who Vax (blog) – http://momswhovax.blogspot.com/2013/12/the-costs-of-fight-against-hpv-vaccine.html– this is a blog post written by Dorit Reiss, a professor of law at UC Hastings who specializes in vaccine law, compensation, injury law, etc. and this is HER mommy blog

I keep hearing about the American College of Pediatricians and its opposition to this vaccine.  What’s up with that?

I want to address this question directly because this is one of the more common concerns I hear from my colleagues in adult medicine.  They are hearing about this from family members, friends, other colleagues, etc. and they want to know what I, as a pediatrician, have to say on the matter.

Non-pediatricians are probably aware that the American Academy of Pediatrics is the largest and most influential professional society of pediatric physicians in the United States.  However, they are not the only pediatric professional society.  You may have read on the internet or heard from friends or patients about a policy statement released by the American College of Pediatricians warning about the supposed dangers of the HPV vaccine.  I have had some parents ask me about such a policy statement issued by the AAP.  As you might imagine, the lay public doesn’t always recognize that the two societies are different entities.  The differences, however, are numerous and important.

The American Academy of Pediatrics represents over 60,000 pediatricians in the United States.  They make recommendations based on extensive research and are recognized as a credible, evidence-based professional organization.  They strongly recommend the 9-valent HPV vaccine.

The American College of Pediatricians broke away from the American Academy of Pediatrics in 2002 after the AAP issued a policy statement in support of same-gender couples being legally allowed to foster and adopt children.  They exist as a political organization with a moral agenda and they have about 500 active members.  They do not publish any research journals and have no academic requirements for membership.  Their policy statements are not based in scientific evidence but rather in ideology and often contain assertions that have been long discredited in the medical literature.

Their recent policy statement asserted that the HPV vaccine has been linked to premature ovarian failure and they rely on reports from the Vaccine Adverse Event Reporting Service to support this claim.  VAERS is not intended to be used in this manner, however.  The reporting service relies on reports from patients and physicians and is required by law to accept and publish all reports it receives, whether there is a plausible connection between the event reported and the vaccine administered or not.  This raw data is monitored very closely by the CDC and any uptick in reports of any problem is investigated further to see if there may actually be a causal relationship with a vaccine.  They use a process called the Vaccine Safety Datalink.  Premature ovarian failure does tend to occur in early adolescence and can be linked to a number of known causes such as chromosomal disorders, effects of chemotherapy and radiation, autoimmune processes etc.  Since the HPV vaccine is administered in early adolescence, it is inevitable that there will be some coincidence between receiving the vaccine and being diagnosed with premature ovarian failure.  However, there is no difference in incidence in vaccinated girls compared to unvaccinated girls.  The incidence of this disease is 22 per 100,000 girls between the ages of 15 and 19 years.  It was the same before the introduction of the HPV vaccine.  We know this because the connection has been rigorously investigated.  There is no causal relationship between the HPV vaccine and premature ovarian failure.[vii]

When is the best time to administer this vaccine?

I often encounter parents who decline the HPV vaccine at the recommended age (9-11 years) with the intention of getting it later.  They reason that their son or daughter is not likely to be exposed to HPV for many more years and they worry that if the vaccine is given too early, immunity may wane over time and fail to protect their children through their adult years.

There are a number of reasons why administration of the HPV vaccine is recommended at age 11.  It is safe and effective in ages 9 years through 26 years and ideally should be administered prior to a patient’s 15th birthday.

First, the tragic reality of our world is that 1 in 4 girls will experience some form of sexual abuse during her childhood.  For boys, incidence is 1 in 6.  The goal of immunization is to protect individuals prior to exposure so knowing what we do about the state of child maltreatment in the United States, earlier is better.

Second, post-licensing monitoring and efficacy trials have demonstrated an interesting phenomenon.  Immunoglobulin production in vaccine recipients is greater in individuals under the age of 15 years.  Their response is so superior to their older counterparts, it is now recommended that patients who receive their first dose of HPV vaccine prior to their 15th birthday only require 2 doses rather than the 3 recommended previously (and still recommended for older individuals).[viii]

Third, as already mentioned above we have good evidence that the immunity generated by the HPV vaccine persists through young adulthood.  This is the time of greatest risk of infection in the United States.  Since its introduction in 2006, immunoglobulin titers have been periodically monitored in early recipients of the vaccine and so far, they have not waned.[ix] [x]

Fourth, here’s my anecdotal two cents on the matter: age 11 is the ideal time to administer the HPV vaccine.  This is the age when adolescents must receive a dose of Tdap and a dose of MCV to attend school, prior to entering the 6th grade in the state of Texas.  Thus, they are coming in for vaccines anyway.  Many teens who don’t participate in sports may not come in to see their primary physician every year for their checkup.  For Medicaid recipients an annual health maintenance visit is required to keep their benefits.  However, most private insurers have no such requirement.  The 11-year-old well visit may be our only chance to get the first dose of HPV vaccine administered in many of our adolescent patients.

Why are we immunizing boys?

Because they can get HPV related cancers and genital warts too![xi]  We know that men can contract penile, anal and oropharyngeal cancers caused by HPV.  Even more frightening is that such cancers in men are notoriously difficult to detect and we do not yet have a reliable screening method.  A growing body of evidence supports the conclusion that HPV vaccination can prevent these cancers.[xii]

No doubt you have already received questions about this vaccine from your friends, family members, and patients who have older children.  They trust your opinion about this vaccine because you are a physician and they have a good relationship with you. What you tell them has great influence over their decisions about vaccinating their children.  They’re asking the nurses you work with as well, so I ask you to please share this article with them.  Numerous studies have demonstrated that when it comes to immunizations, parents are swayed by what the health care professionals they actually know do for their own children.  My boys will be getting this one when they’re nine.

I also encourage you to speak up to our representatives about this vaccine.  When legislation is brought forward to make the HPV vaccine mandatory for school attendance, please give our legislators a call or send an email.  Let them know that as a physician, you support such legislation.  The fact that the vaccine is not required for school attendance is a major reason many parents refuse it for their children.  They may know nothing else about the vaccine or the diseases it prevents, but they assume because it isn’t required for school attendance it must not be necessary.  Our kids are under threat from so many other things.  Let’s eliminate the risks we can.  Thank you for reading this far, friends.  In my line of work, the administration of vaccines is one of the most important things I do all day.  It’s the part of my day when I get to look death in the face and spit in his eye.  Thanks for helping me fight the good fight.

 

References:

[i] Markowitz LE et al, “Recommendations of the Advisory Committee on Immunization Practices”. MMWR Recommendations and Reports. March 23, 2007 / 56(RR02);1-24

[ii] Markowitz LE et al, “Reduction in Human Papillomavirus (HPV) Prevalence Among Young Women Following HPV Vaccine Introduction in the United States, National Health and Nutrition Examination Surveys, 2003–2010”. The Journal of Infectious Disease. Volume 208, Issue 3, 1 August 2013, Pages 385–393

[iii] Ferris DG et al, “4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents After 10 Years”, Pediatrics. December 2017, Volume 140, Issue 6

[iv] “HPV Information for Young Women”, Center for Disease Control and Prevention public website – https://www.cdc.gov/std/hpv/stdfact-hpv-vaccine-young-women.htm

[v] “HPV Vaccine Fact Sheet”, Association of Reproductive Health Professionals – http://www.arhp.org/Publications-and-Resources/Patient-Resources/Fact-Sheets/Understanding-HPV-Vaccine

[vi] Offit P, et al. “A Look at Each Vaccine: Human Papilloma Virus”. CHOP Vaccine Education Center. November 9, 2016.

[vii] Arenheim-Dahlstrom L et al, “Autoimmune, neurological, and venous thromboembolic adverse events after immunisation of adolescent girls with quadrivalent human papillomavirus vaccine in Denmark and Sweden: cohort study”. BMJ. 2013;347:f5906

[viii] Meites E et al. “Use of a 2-Dose Schedule for Human Papillomavirus Vaccination — Updated Recommendations of the Advisory Committee on Immunization Practices”. MMWR. December 16, 2016 / 65(49);1405–1408

[ix] Ferris D, Samakoses R, Block SL, et al. “Long-term study of a quadrivalent human papillomavirus vaccine”. Pediatrics 2014; 134(3):e657-665

[x] Naud PS, Roteli-Martins CM, De Carvalho NS, et al. “Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine: Final analysis of a long-term follow-up study up to 9.4 years post-vaccination”. Human Vaccines and Immunotherapeutics 2014; 10(8):2147-2162

[xi] “Cancers Associated with the Human Papilloma Virus”, Center for Disease Control and Prevention public website – https://www.cdc.gov/cancer/hpv/basic_info/cancers.htm

[xii] “HPV Vaccine is Cancer Prevention for Boys Too!”, Center for Disease Control and Prevention public website – https://www.cdc.gov/features/hpvvaccineboys/index.html

Advertisements

Leave a Reply

Please log in using one of these methods to post your comment:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

Blog at WordPress.com.

Up ↑

%d bloggers like this: