How not to market a vaccine

First, some background.  Human papilloma virus (HPV) is the causative agent for warts.  All warts are caused by infection with this virus, which (common to many infectious agents) has numerous strains.  Some of these strains are associated more with a risk of warts, and others increase a person’s risk of certain cancers, most commonly cervical cancer in women.  In 2006, a vaccine against four HPV strains called Gardasil was licensed for use in girls and young women; two of the included strains were high-risk for cervical cancer, and two are a common cause of genital warts.  In 2009, the license was expanded for use in boys, with the twin goals of lowering risk of genital warts in males and decreasing the prevalence of high-risk HPV (and thus risk of exposure for girls) in the general population.

The response has been tepid to date.  I think there are numerous reasons for this.  The virus is transmitted sexually, but the vaccine is most effective when given before sexual debut.  Many parents associate the virus with sexual activity, and either don’t understand the reason for giving it to their sexually innocent preadolescent child or simply chafe at the thought that said innocent moppet ever will have sex and shut down the conversation.  There were concerns about a rare neurological condition occurring after vaccination in some cases, but that association appears to be unfounded.  Social conservatives object to vaccinating their children out of a belief that fear of sexually-transmitted disease is a curb on extramarital sex, and that lowering the risk of genital warts/cervical cancer will remove a barrier to an undesired behavior.  Finally, the risks of cervical cancer may seem somewhat abstract.  It takes years for the disease to develop after exposure to the virus, and the vaccine has been out for too short a time to have had a demonstrable effect on public health.  Simply put, parents may not perceive that the benefit of vaccination is all that great, especially if they can convince themselves that their children will not grow into the sort of person who has the kind of risky sex they associate (rightly or wrongly) with a sexually-acquired infection.

I am very, very pro-vaccination.  I’ve written about them before, and I don’t need to belabor the point now.  I am a proponent of vaccination against HPV specifically.  If a vaccine can lower the risk of illness and death from cancer, I would want it for my patients and my loved ones.  This attitude is shared by my colleagues, and ours is not a practice that accommodates parents who wish to defer vaccines for their children.  All that being said, HPV vaccination is a patently fraught topic for many of the parents that bring their pre-teens in to see me.  Even those who have gotten every single one of the recommended vaccines right on schedule frequently balk at this one.

For my part, I don’t push too hard.  Unlike a disease like measles or pertussis, where a parent’s decision not to vaccinate has health implications for children other than their own, for the most part the only person whose health is compromised by parental refusal to give Gardasil is their own child (or a person in the future who may choose to have sex with him or her).  While I may not agree with these parents’ decisions, I believe it should be their prerogative to make even bad health care decisions for their kids (excepting obvious gross neglect).  I have too many other situations where I need to persuade parents to change their minds about things, and I choose not to prevail upon parents who are reluctant about this vaccine.

It turns out that there may be other benefits for boys beyond lessening the risks of genital warts, or of exposing sexual partners to a risk of cervical cancer.  From the New York Times:

HPV strains 16 and 18, which the vaccine protects against, have been linked to anal cancer, penile cancer and common cancers of the back of the throat and tonsils, where the virus can spread through oral sex.

Merck, which makes Gardasil, is trying to muster enthusiasm for the vaccine with new data suggesting that the vaccine may protect against anal cancer and, possibly, other cancers as well. The research may soon tip the scales in favor of a national recommendation to make male vaccination routine.

New data from a Merck clinical trial that included several hundred men who have sex with men indicate that three years after vaccination, those who received Gardasil were significantly less likely to have developed high-grade precancerous anal lesions than a comparison group. Only three of the 194 men who were vaccinated developed the abnormalities, compared with 13 of 208 men who received placebo shots.

Debbie Saslow, director for breast and gynecological cancers at the American Cancer Society, said that even though the numbers are small, “the data are believable.”

Gay men will benefit most from the vaccine’s protection from anal cancer, because their risk is higher than that of heterosexual men. (Yet women are even more likely to develop anal cancer: There are 5,820 new cases of anal cancer diagnosed each year, 3,680 of them in women.)

But so far public health experts have dismissed the idea of a vaccination campaign singling out young gay men specifically. “It’s very stigmatizing,” Dr. Saslow said.

It’s also impractical, since the vaccine is supposed to be given to young people before they become sexually active, she said.

“Most young men don’t realize they’re in that category or tell their health care provider they’re in that category until after they’ve been sexually active, usually with multiple partners,” Dr. Saslow said, “and then it’s much less beneficial to vaccinate them.”

Unless the PR staffers at Merck have all collectively started sniffing glue, I cannot imagine they will use these data to broaden the vaccine’s appeal.  If it’s troublesome enough for parents to accept that one day their little girl may grow up and have sex (maybe even with someone other than her similarly-virginal husband), then I cannot imagine the reaction to the suggestion that their little boy may grow up to be gay and engage in receptive anal intercourse.  [I presume we are all grown-ups here, and I thus have the privilege of writing frankly.  Please do not prove me wrong in the comments.]  I would rather drink a Drano margarita than discuss this subject with most parents, and I’m an openly gay man whose medical specialty is the care of adolescents and who works in a major New England metropolitan area.  I cannot imagine a pediatrician broaching this topic with parents in Pig’s Knuckle, Mississippi.

I would love for all of my patients, male and female, to receive this vaccine.  The potential added benefit for boys, even a small sub-population of them, is a good reminder for me to continue encouraging parents to have their kids vaccinated.  But some benefits are probably best left undiscussed.

Update (7/25/2011):  As a courtesy to some of my commenters, I’d like to share this useful link.  (H/t Andrew Sullivan.)  I wonder if the “Michele” who offered a comment here at around 2:45 AM is the same Michele who posted there at around 2:50 AM.  Hmmmmm….

Russell Saunders

Russell Saunders is the ridiculously flimsy pseudonym of a pediatrician in New England. He has a husband, three sons, daughter, cat and dog, though not in that order. He enjoys reading, running and cooking. He can be contacted at blindeddoc using his Gmail account. Twitter types can follow him @russellsaunder1.


  1. Do you know anything about the vaccination of adult men? I recall reading somewhere that the vaccine wasn’t recommended for people over 25 or somesuch. Is that true?

    • The primary reason not to vaccinate older men (or women) is that the vaccine is most effective before exposure to the virus, and by the middle 20s most people have begun having sex and have sufficient risk of exposure to make the vaccine not worth the cost. (That is my understanding, at least.)

      • FDA documents reveal HPV vaccine may increase your risk of cancer if you already have HPV. In trials, Gardasil increased risk by 44.6% of developing high-grade precancerous lesions in women who are already sero-positive and PCR-positive for vaccine-relevant genotypes of HPV. However, pre-screening for HPV infections has not been included in the vaccination program.
        Also, the adverse events following Gardasil vaccination are not so rare.

        • I am not familiar with this finding, which has never been presented at any of the numerous conferences I have attended where HPV vaccination has been discussed. Please provide a link to the specific documentation you cite regarding increased risk of precancerous transformation attributable to vaccination.

          • There were two important concerns that were identified during the course of the efficacy review of this BLA [biologics license application]. One was the potential for
            (Page 6 of 24)
            Gardasil to enhance disease among a subgroup of subjects who had evidence of persistent infection with vaccine relevant HPV types at baseline. The other concern was the observations of CIN 2/3 [cervical intraepithelial neoplasia, abnormal cell changes in moderate stage] or worse cases due to HPV types not contained in the vaccine. These cases of disease due to other HPV types have the potential to counter the efficacy results of Gardasil for the HPV types contained in the vaccine . . . The results of exploratory subgroup analyses . . . suggested a concern that subjects who were . . . positive for the vaccine-relevant HPV types had a greater number of CIN 2/3 or worse cases. 17

            A chart in the committee’s report revealed that efficacy in subjects already exposed to “relevant HPV types” had an observed efficacy rate of -44.6%. The disturbing efficacy rate raises questions as to who should be receiving the vaccine, and why the FDA allows Gardasil to be administered without prescreening for HPV. The outcomes that can result from pre-exposure are disconcerting and deserve far more attention.

          • Thanks for your comment, Judy. Please include a link to the entire document so that I may review all excerpts in context and read the final conclusion. Please do not copy material from other websites.

            Also, whatever the full document may say, it seems to have been part of the initial filing for FDA approval. Since that time, I do not believe that there has been a problem with increased CIN 2/3 in vaccinated individuals. I have attended numerous conferences where the vaccine was discussed (none sponsored by the manufacturer) and nobody has reported an increased incidence of abnormal cytology.

            Finally, vaccinating girls who are young enough that sexual activity is highly unlikely obviates the risk of vaccinating women who have already been exposed.

      • It’s not just a change in cost-benefit; there is actually evidence to suggest that if Gardasil is given after HPV exposure, the risk of developing cancer *increases*, which is why Dr. Diane Harper, lead researcher of the Gardasil vaccine, advocates that people be tested for the presence of HPV prior to vaccination. You’re a pediatrician – you should know this, and require tests prior to administering the vaccine. Since you didn’t mention this in the comments, it sounds like you didn’t know that, which is scary and concerning, from someone who sounds like you give this vaccine a lot. I wonder how many children you’ve injected with Gardasil who will develop cancer *because* of this vaccine, since they were already infected (unknowingly) with HPV at the time of vaccination.

        • 1) I find it implausible that Dr. Harper advocates that patients be screened for HPV infection prior to receiving the vaccine. The only way to screen for HPV infection is through a pelvic exam and cervical swab, which absolutely nobody would actually recommend for girls who have not become sexually active. A requirement to screen for HPV infection prior to administration is absurd. If you have documentation to support the claim you are making about Dr. Harper’s position on HPV screening, please include a link.

          2) You are grossly misstating the substance of Dr. Harper’s objection to the vaccine, which is that vaccination may create a false sense of security in some women and lead them to defer Pap testing.

          3) While I do not know Dr. Harper, I have read a great deal of what she has to say and respect her opinion, which is based on her own expertise and research. However, she is only one person. Numerous other researchers and clinicians with similar expertise have different views and recommendations. Study about the long-term immunity and protective effect is ongoing, but research presented at a conference I attended within the past year indicates that the protective effects last at least 10 years, which would cover many adolescents’ period of greatest sexual risk behavior.

          4) I’m really quite confident that the number of children who will go on to develop cancer because of the vaccine is nil.

    • There are certain medical conditions (eg. immune deficiencies, allergy to a vaccine component, etc) that contraindicate vaccination.

      For otherwise healthy people, I can think of little good reason to decline vaccination.

  2. I’m with you on vaccinations Russel. I’d go so far as to call the huge herd immunities of the developed western world one of the cathedrals of modern medicine; a biological soaring triumph unparalleled in history. While I feel some very modest sympathy for mothers and fathers wracked with fears of autism Anti-vaccination screeds from anyone else makes me see crimson.

  3. I certainly understand about picking your battles. Perhaps when people eventually stop freaking out over MMR vaccine, it will become a little easier to sell this one?

  4. The “One Less” commercials irritated me.

    Shouldn’t it have been “One Fewer”?

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