Talking to Your Girls: The Best Vaccine of All

In a previous posting, I noted that there are almost no studies looking at whether giving the human papillomavirus (HPV) vaccine to adolescents increases unsafe sexual behavior -- what some call a passport to promiscuity for girls and a license to drill for boys.  Although there are still no studies looking at behavior post-vaccine, the Archives of Pediatric and Adolescent Medicine just published a study on the attitudes and beliefs of girls who got the HPV shot.
The authors asked the girls (ages 13-21) to agree or disagree with statements like, "After getting the shot against HPV, I am less worried about getting a sexually transmitted disease other than HPV," and "After getting the shot against HPV, I think that condom use (or having fewer sexual partners) is less necessary."

First, the good news:  Only 4% of the girls felt less of a need to practice safe sex because of the vaccine.  The investigators then looked at what factors were associated with this belief.  Some risk factors were predictable, but a few were surprising.  A lower perceived need for safe sex was associated with:

• Lower knowledge about HPV and the vaccine
• Lack of condom use at last intercourse
• Lack of maternal communication about the HPV vaccine
• Teacher or physician serving as the source of HPV vaccination information

The last one threw me for a loop.  Surely the most reliable information about the vaccine and STDs comes from doctors and sex education teachers?  The problem is that even if they are dispensing appropriate advice (which may or may not be a correct assumption) , they may not be doing so in a way that's understandable to teens and their mothers.  On the flip side, it looks like moms can have a positive impact in their daughters' behavior, particularly if they talk to them about the limitations of the vaccine, including its lack of protection against some HPV strains, other STDs and pregnancy.

Though very few girls agreed that the vaccine would allow them to have more unprotected sex, survey answers don't necessarily predict behavior.  Even before the vaccine, over half of the adolescents in this clinic were sexually experienced, and most were not using condoms reliably.  It's doubtful that the vaccine will decrease the rate of unsafe sexual practices, unless it's accompanied with appropriate counseling.

So does this mean we shouldn't be vaccinating our daughters against, because of the theoretical increased risk of unsafe behavior?  Of course not.  The advent of effective antiretroviral therapy for HIV in the late 1990's was accompanied by an increase in the rate of unprotected sex, and subsequent gonorrhea and syphilis epidemics, in gay and bisexual men.*  Yet it would be completely unethical to withhold effective drug therapy because of its unintended behavioral consequences.  No, it simply means that doctors and, more importantly, parents have our work cut out for us when it comes to educating our kids.

*Despite the increases in other STDs in the San Francisco Bay Area, there was no increase in the HIV incidence in gay men during this time period.  The theory is that HIV-positive men had unsafe sex only with HIV-positive men, and HIV-negative only with HIV-negative.

The Kindest Cut, Part 2

Looks like I chose a touchy subject for my last blog post; there appear to be quite a few men mourning the loss of their infantile foreskin.  Let me summarize some of the arguments made against my opinion on male circumcision, with my responses:


1.  You cherry-picked studies showing a benefit for male circumcision.  It's true that while numerous observational studies have shown a benefit in terms of UTIs and STDs, there are some studies finding no effect, or even an opposite effect.  Non-experimental, observational studies are fundamentally flawed for this reason.  That's why it's so important to look at randomized, controlled trials whenever possible.


2.  The risk of UTIs in male infants is low and does not justify circumcision.  I totally agree.  The reduction in UTIs alone is not large or clinically important enough to advocate for this procedure.


3.  The trials in Africa are flawed because they weren't double-blinded, and they were stopped early.  OK, YOU design a study that does sham circumcision in the control group, and try to get that past an ethics committee.  Stopping a trial early because of a significant benefit in the treatment group (and offering it to the control group) is the most ethical thing to do in this situation, since HIV is a life-threatening disease.  It is true that stopping a study early for this reason tends to overestimate the benefit, and I might be suspicious of the results if they were seen in only one trial, but in fact, the benefits were seen in all three studies, in different parts of Africa.  The Cochrane Group, which is extremely conservative in its recommendations, concluded, "Research on the effectiveness of male circumcision for preventing HIV acquisition in heterosexual men is complete.  No further trials are required to establish this fact."

4.  The trials in adult heterosexual African men don't apply to infants in the developed world.  The majority of HIV infections in the U.S. and worldwide are due to unprotected sex.  Sure, the absolute reduction in HIV infection with circumcision will be lower in the U.S. than in some parts of Africa, but relative risk reductions tend to remain constant over various patient populations.  I do agree that if you're in a part of the world with extremely low rates of HIV infection (such as Australia -- which has a 0.004% annual risk of infection), routine circumcision may not make economic sense.


5.  Why not promote safe sex instead?  I'm not saying circumcision should be done instead of teaching safe sex.  HIV prevention needs to be multi-pronged, and must also include education, free condom distribution, low-cost antiviral treatment (which reduces transmission rates) and needle exchanges.


6.  Infants die from circumcision, and parents shouldn't be making this decision for them.  Yes, babies will rarely die from circumcision, just as people will rarely die from having IVs inserted into their hands or having a severe allergic reaction to antibiotics (both of which I have seen).  But AIDS is still a huge killer, even in developed countries.  As for parents who want to let their sons make the decision about circumcision once they come of age, I think that's fine.  Just realize that adult male circumcision is a bigger procedure, often involving general anesthesia, and may not be covered by insurance plans when done for purely preventive reasons.


7.  Your story about Dr. Nick operating on your kid sounds fishy.  Nope, absolutely true.  I got a list of low-cost providers because I gave birth at my own, public county hospital.

8.  You're a terrible mom.  OK, I will concede that in the moment that I let Dr. Nick circumcise my son, I was a terrible mom.  I'm an imperfect parent, which is why I think a lot of people read my blog.  If I had to do it all over again, I would still have my son circumcised, but I'd go with this guy instead:

Extra credit if you can name this Simpsons character*

9.  The foreskin is a part of normal male anatomy, and removing it is mutilation.  It occurred to me that this argument probably should have been #1, as many of you have a philosophical objection to circumcision.  You think it's wrong to remove normal foreskin for any reason, and I don't.  There's nothing we can say that will change each other's minds on this point. 

And so we have a parting of the ways.

 *It's Krusty the clown's dad, Rabbi Hyman Krustofski.

The Kindest Cut?

When J.J. was born, our hospital gave us a list of outside physicians who performed circumcisions.  My husband called every provider on the list and made an appointment with the second cheapest one -- the same process by which he selects a bottle from a restaurant wine list.  I knew we were in trouble when we were greeted by none other than....

"Hi everybody!"

Actually, Springfield's Dr. Nick was way more professional than this joker, who was dressed in a hospital gown and dirty sneakers.  Without introducing himself or asking if we had any questions, he whipped out his instruments and started operating.  Rick fled, leaving me to comfort J.J. with a bottle.  In the middle of the procedure, the doctor (at least, I hope it was a doctor) said, "Here, hold this," and he handed me the thingy clamped to my son's penis, as he snipped away.  (I'm not a pediatrician or a surgeon, but I assure you that "thingy" is a formal medical term used by internists.)  And no, I wasn't wearing gloves, nor had I told this guy that I was a doctor. I fretted for days that J.J. would develop Fournier's gangrene, and that I would be to blame for his future as a eunuch.  

Fortunately, the risks of circumcision in a developed country are rare (0.2-0.6%) and minor -- typically bleeding, which usually stops on its own.  (We doctors have a saying: "All bleeding stops....eventually."  Think about it.)  But some would argue that there's no reason to put a baby under the knife when it isn't necessary.  And then there are those whack jobs (no pun intended) who blame their unhappy sex life on the loss of their infantile foreskin, not realizing that they can't get a date because they are whack jobs who blame their unhappy sex life on the loss of their infantile foreskin.  In fact, observational studies have been all over the map in terms of whether circumcision is linked to sexual dysfunction.


There are no randomized, controlled trials of circumcision in infants, and there probably never will be.  Since there aren't any studies employing sham mohels, we must rely on the results of observational studies to guide us on the risks and benefits of neonatal circumcision, with their imperfect corrections for baseline differences.  The procedure is linked not only with certain religions, but also with socioeconomic status, with babies born at higher income levels being more likely to be circumcised -- although Dr. Nick and his like-minded colleagues remain a low-cost option for the uninsured.


Circumcision does seem to reduce the risk of urinary tract infections in the first year of life - from 1% to 0.1%.  Not a huge absolute benefit for a surgical procedure, though infant UTIs do present a significant healthcare cost burden.  My pediatrician friends tell me that kidney ultrasounds are routinely performed in male infants with UTIs, to screen for anatomic abnormalities.  They often have to perform suprapubic aspirations (sticking a needle through the skin into the bladder) to obtain a clean sample of urine, which is a low-risk procedure, but not a particularly fun one for baby or parent.


Observational studies have also shown that circumcision is associated with a lower risk of sexually transmitted diseases, including HIV and human papillomavirus, the cause of most cervical, anal and now, oropharyngeal cancers.  But here the data get particularly sticky, since uncircumcised males are more likely to come from a lower socioeconomic status, which in turn, is associated with a higher rate of STDs.


Although there aren't any experimental studies of infant circumcision, there have now been three large randomized, controlled trials of circumcision in over 10,000 adult men.  All of these studies were performed in Africa, with the primary outcome being the subsequent rate of HIV infection.  It turns out that the foreskin is replete with special cells that are prone to invasion by the AIDS virus, so removing the foreskin should reduce the rate of HIV infection.  And indeed it did, by an impressive 50% over a 2-year period.  In fact, all three trials were stopped early, and circumcision was offered to the men in the control groups.  The studies also found reduced rates of HPV infection in both the circumcised men and their female partners.  


Now, a 50% relative reduction is a big deal in parts of the world with high baseline rates of HIV infection.  In these African studies, only 56 members had to be trimmed to prevent one infection at 2 years.  Of course, if you circumcise a baby, the point it to try to reduce his lifetime risk of infection.  The 2004-2005 U.S. data show that the lifetime risk of HIV infection in men is 1.87%.  Some of those are acquired from injection drug use or maternal-child transmission, but the vast majority of infections are due to unprotected sex.  Circumcision should decrease a child's risk of HIV infection, though the magnitude of benefit in the U.S. and other developed countries is unclear, not to mention the risk reduction in the future partners of these boys.

As for the drawbacks of circumcision in the African trials, there were but a few.  Some of the more pleasant "side effects" of the procedure were enhanced sensitivity and sexual satisfaction -- finally, a randomized (if not blinded) trial putting to rest the question of sexual dysfunction.  In fact, some of these trials found increased rates of unprotected sex and number of sexual contacts in the circumcised groups.  The increases were marginal, but remember that they were observed in an experimental setting.  Now that the benefits have been well-established, what if men got the mistaken notion that circumcision was completely protective against HIV, blunting the potential benefits?    I doubt this will be much of an issue in pediatrics, as I can't imagine any parents encouraging their son to sow his wild oats simply because he had been circumcised.

Whatever the studies show, most parents will probably still base their decisions on cultural and personal reasons.  Rick and I had no discussions at all about the benefits and risks of the procedure. I deferred to my husband's wishes, and when it comes to circumcision, that seems to be the rule among the couples we know.  In 1999, the American Academy of Pediatrics acknowledged the "potential medical benefits," but state that "these data are not sufficient to recommend routine neonatal circumcision."  Some have argued that the AAP needs to advocate more strongly for circumcision, now that we have proof that it saves lives.  

As for all you expecting, uncircumcised dads, maybe it's time to start a new family tradition.


*As a doctor, I know I should always use the correct anatomical term.  I fear, though, that too many mentions of the P-word will result in hordes of perverts stumbling on to my blog via their search engines.  (A lot of boys looking for "Girls Gone Wild" were no doubt disappointed to find themselves instead reading about cervical intraepithelial neoplasia.)

One More Round on HPV

On previous blog posts, I advocated for mandatory HPV immunization in girls, but not necessarily in boys.  Well, I've changed my mind.  The vaccine should also be mandatory in boys.


A recent study confirmed what most epidemiologists have suspected for a while -- HPV is fueling the stratospheric, 225% rise in oropharyngeal cancers, involving such structures as the tongue and tonsils.  In the past, most of these cancers have been associated with tobacco and alcohol.  Rates of oral sex have been increasing, as many regard it as being safer than intercourse*, so the combination of that behavior and decreasing smoking rates means that 70% of oropharyngeal cancers are now due to HPV infection.  ("Human papillomavirus and rising oropharyngeal cancer incidence in the United States.")  HPV-positive oropharyngeal cancers can be seen in patients as young as 35 or 40.  While they tend to have a better prognosis than those who have tobacco-related cancer, standard treatment includes a toxic brew of radiation, chemotherapy and/or major surgery, including glossectomy (tongue removal).  There is no such thing as an oral Pap smear, so oropharyngeal cancer is often diagnosed late.  Probably one of the most famous patients is celebrated chef Grant Achatz of the restaurant Alinea, who was diagnosed with advanced tongue cancer in 2007.

This tongue dish from Alinea came from a duck, not the chef.

Fortunately for him and his fans, Achatz managed to avoid a glossectomy, and with aggressive therapy, he is now in remission.  Unfortunately, if current trends continue, projections show that the number of HPV-related oropharyngeal cancers will exceed the number of cervical cancers by 2020, and over half will be in men.


Of course, current trends don't have to continue, not if we make HPV vaccination mandatory in all preteens.  Although oropharyngeal cancer has not been a studied endpoint in any of the vaccine trials, one can make an educated guess about the expected efficacy.  HPV causes 70% of oropharyngeal cancers, 90 to 95% of which are due to HPV-16.  The HPV vaccines protect against HPV-16 with 90 to 98% efficacy in an unexposed population.  Using the most conservative numbers, the HPV vaccines should prevent 57% of orophayngeal cancers if given early. 

So do your family a favor.  Vaccinate your kid, and save a tongue.

*It's not an urban legend.  Oral sex is safer than other kinds of sex in terms of HIV infection.  One episode of receptive oral sex with an HIV+ partner carries a 0.06% risk of infection, compared to 0.1-0.2% for receptive vaginal and 0.3-3% for receptive anal.  And oral sex is widely believed to have a lower rate of pregnancy.

Protect the Girls -- Vaccinate the Boys!

 Mommy, why are we looking at hats for Siamese twins?

That's a photo of my then-5-year-old son J.J., shrinking in terror when I dragged him into Victoria's Secret.  Poor guy -- there's surely nothing more mortifying than bra shopping with your mom (unless it's bra shopping with your grandma). I do realize that one day, hopefully far in the future, my innocent little boy will have a very different reaction to all those scantily clad plastic torsos.  And when he reaches that age, it will be my husband's and my solemn responsibility to guide and protect him against STDs.  So naturally we'll be enrolling him in an abstinence-only sex ed program.*

Kidding, folks!  Remember, I'm Evidence-Based Mommy, not Delusional Mommy.

Last week, I reviewed the data on the HPV vaccine for girls.  In addition to cervical cancer and genital warts, HPV causes the vast majority of penile and anal cancers, although these are much rarer.  Gardasil has been FDA-approved for use in males ages 9 through 26.  So what is the evidence that it works in this population?  And now that J.J. is on the cusp of turning 9, should I be asking his pediatrician for this series of expensive shots?

As with the HPV vaccine trials in women, there are no large studies in preteens, but again, the idea behind immunizing children is to protect them before they are potentially exposed to the virus in their teens or young adulthood.  The largest trial randomized over 4000 males ages 16 to 26 to the 4-strain HPV vaccine vs. placebo.  ("Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males.")  The marketing geniuses at Merck couldn't come up with a snappy acronym this time, but I liked my Scrabble-savvy friend's suggestion of SPAWN, for Stop Penectomies** and Anal Warts Now.  Six hundred of the participants reported having sex with men, a major risk factor for HPV infection.

As in the female trials, the vaccine was quite effective in patients who were uninfected at baseline, with an 84% reduction in genital lesions (mostly warts) in those who received all three shots.  The benefit in the population as a whole was significantly less, but still a decent 60% reduction.  Three precancerous penile lesions occurred in the placebo group and none in the vaccine group, but SPAWN wasn't large enough, or of sufficient duration, to detect a difference in these rare neoplasms.

Despite the clear benefit in reducing genital warts, the most frequent and more politically palatable argument for immunizing boys is to protect girls against cervical cancer.***  So should the HPV vaccine be mandatory in boys?  As much as I feel that males should shoulder some of the moral responsibility for their partners' health, in this case, I have to say no.  One of the reasons I've come to this conclusion is that cost-effectiveness analyses have shown that immunizing boys in addition to girls is extremely expensive, compared to immunizing only girls.  The excess cost ranges between $100,000 to a million dollars per year of life gained.****

Having said that, I do plan to sacrifice my eldest son on the altar of public health when his time comes.  Unfortunately for my human pincushion kids, I'm an allopathic doctor who is unabashedly pro-immunization.  Some day they'll thank me for it.

*Evidence has shown that abstinence-only programs are useless in delaying sex.  This is not to be confused with the seemingly oxymoronic abstinence-only parenting.  Telling your child, "Like hell you'll be crashing at your boyfriend's tonight!" has been shown to delay sex.
**A penectomy is an amputation of the penis, standard treatment for penile cancer.  If men were made aware of this, we would have no problem achieving 100% vaccination rates.
***For my gay readers, I apologize for this obviously hetero viewpoint.  There is a much more compelling argument to vaccinate gay males, as the incidence of anal cancer is similar to that of cervical cancer before the era of Pap smears.  The problem with vaccinating only gay males is that by the time a teenager or young adult is comfortable enough to come out of the closet, he may already be infected with HPV.
****Technically speaking, "quality-adjusted life-years" gained.  Since the most frequent manifestation of HPV infection are genital warts, and since warts don't kill you, researchers ask participants to estimate how many years of life they would be willing to give up not to have warts. One study found that having warts was as bad as losing anywhere from 1.6 to 8.3 days of life. ("Cost of treatment and QALYs lost due to genital warts.")  Hard to believe, but I guess I could see how it could get to be over a week if the warts made their cameo on, say, prom night.

Gardasil = Girls Gone Wild?

Stick to your guns, Governor Perry!

Four years ago, Texas governor Rick Perry raised a ruckus when he issued an executive order for all sixth-grade girls to undergo mandatory vaccination against the human papilloma virus, the cause of most cervical cancers and genital warts.  It was a strong and surprising move, especially coming from a politician who believes in teaching kids that cavemen coexisted with dinosaurs.  Critics from the right (and a few from the left) railed against the order, claiming it infringed upon parental rights and taught girls that premarital sex was O.K., despite the fact that the order gave parents the right to opt out of vaccination.  The order was overturned by the state legislature, and mandatory HPV vaccination never went through.  Now that he's running for the White House, Perry is apologizing for his earlier decision, stating, "I didn't do my research well enough."  Was he right then, or is he right now?  Well, Governor, how about if I do the research for you?

The landmark trial that got the HPV vaccine approved by the FDA was the "Females United  to Unilaterally Reduce Endo/Ectocervical Disease," Study, with the totally awesome acronym, "FUTURE II," bringing to mind a popular Disney attraction rather than genital warts.  ("Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions.")  Over 12,000 women ages 15 to 26 years were randomized to three doses of the HPV vaccine or placebo.  The vaccine was designed to protect against two HPV strains that cause 70% of cancers, and two other strains that cause the majority of genital warts.  The primary endpoint, which was carefully selected by Merck, maker of the vaccine, was the rate of cervical cancer or precancer caused by the two HPV cancer-causing strains in women who were not previously infected by these strains.  Got it?  Not the overall rate of all cervical cancer or precancer in all the women, but only a subgroup of cancers in a subpopulation.

The vaccine was extremely effective:  in women without prior infection, the vaccine prevented 98% of cancers and precancers caused by the two strains of virus, and almost 100% formed protective antibodies.  But what if you looked at the entire group of 12,000 women, and all forms of cervical cancers and precancers?  It turns out the efficacy was a disappointing 17%.

So why was the overall efficacy of the vaccine so low?  Two reasons:  First, the women who received the vaccine were still unprotected against the strains of HPV that cause the remaining 30% of cervical cancers.  Second, a good number of the women were already infected with the strains in the vaccine, rendering it useless.

So does that mean we shouldn't bother giving this expensive vaccine because of its low overall efficacy?  Actually, the results of the study strongly suggest that we should be giving the vaccine to girls before they become sexually active.  The CDC reported in 2006 that 70% of girls are sexually experienced by the time they are 19, and another study found that 27% of women aged 20-24 test positive for HPV.  If you follow the American Academy of Pediatrics' guidelines and give the vaccine to presumably uninfected 11- to 12-year-old girls, they should experience a 70% reduction in cervical neoplasms.  I suspect that pharmaceutical companies are probably working on adding more strains to the vaccine, to get the efficacy closer to 100%.

What about the argument that the vaccine will lead to a false sense of security, or an increase in early, sexually risky behavior?  Certainly, there are lot of misconceptions about the vaccine -- for example, that it protects against all cervical cancers, or that you can stop getting Pap smears.  The vaccine shouldn't be given without a fairly sophisticated discussion of the expected benefits.  Presumably, the discussion would be between the parent and the pediatrician, and then ideally, between the parent and the child.  I suspect that a big reason why some parents are reluctant to vaccinate their kids is that they want to avoid an uncomfortable conversation.

As for whether an STD vaccine would be, as one author put it, "a passport to promiscuity," there is very little data.  Four Scandinavian countries recently surveyed 65,000 women about their sexual behavior prior to the introduction of the HPV vaccine.   (Interviewing Swedish supermodels about their sexual proclivities: obviously the brainchild of some repressed male researcher!) They plan on re-surveying them after the vaccination campaign, to see whether it affects their behavior. ("Women's sexual behavior.  Population-based study among 65,000 women from four Nordic countries before introduction of human papillomavirus vaccination.")  HIV vaccine trials have not found an increase in sexually risky behavior among its participants, though many of them were high risk to begin with.  And one survey of adolescent girls found that only about 10% thought that getting the vaccine meant that they were old enough to start having sex.  ("Adolescents' beliefs about their parents' human papillomavirus vaccination decisions.") Frankly, I think most teenagers and young adults are more frightened at the prospect of pregnancy and HIV than they are of HPV, and I doubt the vaccine will do much to alter their behavior.

So should the vaccine should be mandatory in girls?  I say yes, as long as parents have the option to decline.  Making it mandatory would remove its stigma as "the STD vaccine," and countries that have instituted school-based HPV vaccination programs have much higher rates of immunization that those that haven't.  Remember that this wouldn't be the first mandatory vaccine for a sexually transmitted disease; the hepatitis B vaccine is required for elementary school enrollment in most states. 

I do understand the argument that it shouldn't be as compulsory as, say, the measles vaccine, since your child can't catch HPV just by sitting next to an infected person in class.  But if we wait until girls are old enough to consent to the vaccine themselves, it may be too late.  I've seen too many 30-year-olds die agonizing deaths from cervical cancer to let my daughter suffer such a fate.  Even more women have to deal with the infertility resulting from treatment of their cancer or precancerous lesions.  We parents do all that we can to instill our own values into our children, but at a certain point, we have to accept that they will make their own decisions, good or bad.

So man up, Governor Perry!  Apologize for your apology, do the right thing, and become the public health advocate every presidential candidate should be.

Next week:  The HPV vaccine for boys