Q&A on the Human Papilloma Virus Vaccine Gardasil

Heard the one about the right-wing Southern governor who ignored required legislative procedures and ordered 11-year-old girls to be vaccinated against a sexually transmitted disease? Here’s the punchline: it actually happened.

Yes, Texas Governor Rick Perry, successor in fact and in small-government philosophy to President George W. Bush, actually signed an Executive Order requiring sixth grade girls in Texas to be vaccinated against the human papilloma virus (HPV), the cause of most cases of cervical cancer. In so doing, he cast aside the concerns of his political base that the vaccine would unleash a torrent of unfettered sexual activity among teens otherwise preoccupied with HPV.

Here’s a hot tip: whenever you see apparently incongruous political behavior, the first question you should ask is “Where’s the money?” Turns out that simple line of inquiry would have solved this erstwhile mystery. For starters, Perry’s former chief of staff Mike Toomey has found a new (and presumably more lucrative) lease on life with Merck, manufacturer of the HPV vaccine Gardasil. And on the very day that Perry’s staff met with Merck about the Executive Order, a $5,000 check from the company made its way into the governor’s coffers. Add to that Merck funding of a group of female state legislators called Women in Government, many of whom introduced mandatory vaccination bills in their respective states, and you have all the ingredients for a sordid political stew.

But just because self-interested corporate behavior is at the root of an initiative does not prove that the initiative is not worthwhile. Cervical cancer takes the lives of some 3,700 American women each year. Preventing these deaths is obviously an end worth pursuing. In this article we provide a Q&A on the HPV vaccine that is based on questions about the vaccine we have received at the Health Research Group.

Why do we need a vaccine when cervical cancer is rare and
actually declining?
It is true that cervical cancer is becoming less common in the US. This is probably the result of increased condom use, due to concern about HIV/AIDS, and improved access to pap smears. But in 2006, there were still 9,710 cases of cervical cancer and 3,700 deaths. Even the majority of patients who are cured have to endure years of treatment and anxiety about recurrence. Certainly, the fact that a deadly disease is becoming less common is not a convincing argument to downplay it, and few parents hesitate to vaccinate their children against chicken pox, which takes considerably fewer lives than cervical cancer.

Can’t pap smears prevent cervical cancer? If so, why is the HPV vaccine necessary?
Pap smears are one of the great medical innovations of the 20th century, having saved the lives of tens of thousands of women. The problem is that this effective intervention is underutilized, particularly among poor Americans with limited access to health care. It is in this group that the HPV vaccine will have the greatest benefit.

Is the HPV vaccine effective in preventing cervical cancer?
The FDA approved the HPV vaccine primarily on the ground that the vaccine reduced the rate of new cases of cervical cell abnormalities called dysplasia. Experts agree that dysplasia is a necessary precursor of cervical cancer (although some cases of dysplasia resolve spontaneously) and that any intervention that reduces dysplasia should reduce cervical cancer rates. In the context of clinical trials, which only last a few years, cervical cancer is quite rare, so it is difficult to demonstrate a decrease in new cases of cancer that is statistically credible. That’s why the researchers examined the impact of the vaccine on dysplasia, which is considerably more common than cervical cancer.

Will the HPV vaccine prevent all cases of cervical cancer?
The current HPV vaccine is designed to protect against HPV subtypes 16 and 18, which are responsible for 70 percent of cases of cervical cancer, and HPV subtypes 6 and 11, which cause 90 percent of genital warts. It is not known to be effective against any of the other HPV subtypes.

How effective was the HPV vaccine in reducing the rate of dysplasia?
Among women who had not been exposed to the relevant HPV subtypes and who received all three shots in the vaccination series, the vaccine prevented between 95 percent and 100 percent of cases of cervical dysplasia due to HPV subtypes 16 and 18. Not surprisingly, effectiveness rates were lower (39 percent to 46 percent) if one combined the data from women with and without HPV exposure at the beginning of the study and included women who may not have completed the vaccination series. This provides an argument for earlier vaccination in that people who have not initiated sexual activity are unlikely to be infected with HPV. Importantly, the HPV vaccine does not treat existing cases of cervical cancer, dysplasia, or genital warts.

Does the HPV vaccine protect against other forms of cancer?
Certain strains of HPV have been linked to cancers of the anus, female external genitalia, penis, vagina, throat, and mouth. Researchers are studying both women and men to determine whether the HPV vaccine is effective in preventing cancers due to HPV infection in these areas. However, the vaccine is currently only approved for the prevention of cervical cancer.

Won’t the HPV vaccine cause women to not get their pap smears?
This question has not been studied and is a legitimate subject for future research. But there would have to be large numbers of women foregoing pap smears before the benefits of the vaccine in women not exposed to HPV would be exceeded. Women who have received the HPV vaccine should continue to have pap smears just as frequently as before they were vaccinated.

Won’t the HPV vaccine cause an increase in teen sexual activity?
While this has also not been studied, this seems very unlikely to us. Of all the factors young women (and men) take into consideration when deciding whether to have sex, a vaccination, years previously, against an infection they may not have heard of seems unlikely to rank high.

Why can’t the vaccine be made voluntary instead of being required?
Studies show that mandatory vaccination programs, usually linked to school attendance, have much higher participation rates. Moreover, outbreaks of meningitis, measles, and much more have resulted from refusals to participate in vaccination programs. All of the HPV vaccination programs proposed allowed some exception for parental refusal but varied in the breadth of that exemption.

Why do the proposed vaccination programs involve girls so young (and why only girls)?
Merck’s data show much lower effectiveness rates when the patient is already infected with HPV, so it is important to vaccinate young women before they become infected, ideally before they begin sexual activity. The fact is 60 percent of high school seniors are already sexually active. Because early studies focused on dysplasia prevention in women, the effects of the vaccine on men and boys are not yet known, but studies are ongoing.

Is the HPV vaccine effective in younger teens?
The primary studies of the vaccine involved women aged 16-26 years, yielding the results noted previously. In additional studies of women aged 9-15 years, similar antibody levels were seen as in the older age group, and so the effectiveness in young women was inferred. (Antibodies are chemicals made by the body in response to exposure to outside stimuli such as vaccines or infections and frequently correlate with vaccine effectiveness. It is common in the vaccine field to use antibody data to explore vaccine effectiveness.) Cervical dysplasia (let alone cervical cancer) is too rare for investigators to see enough cases in a study of young women to prove that the vaccine reduces new cases. 

Is it true that the HPV vaccine is the first for a sexually transmitted disease?
No; hepatitis B is also spread by sexual contact (as well as by drug injection, hospital needlesticks, and from mother to infant) and the vaccine is now administered to babies before they leave the hospital after birth.

Has vaccination against a sexually transmitted disease ever been mandatory?
Yes; 43 states currently require childhood immunization with the hepatitis B vaccine.

Is the vaccine safe?
Studies of the vaccine show that toxicity was limited, usually restricted to pain and tenderness at the injection site (84 percent and 25 percent respectively). There are, however, few data on long-term toxicity due to the limited length of the trials conducted. This leaves many questions unanswered. The FDA recommends against use in pregnant women, though there is no evidence that it is toxic to the developing fetus.

Do we know whether the vaccine will work in the long term?
The longest study of the HPV vaccine was four years long. Such study durations are common for newly approved vaccines. Some patients who have received the vaccine will be followed to see if their antibody levels decline and thus if they (and others) would require a booster injection.

This vaccine is very costly.  How am I supposed to pay for it?
At $360 for the full three-injection series, that is certainly so. Some states’ proposals inappropriately required vaccination, but did not provide for funding. In other states, some funding was provided. If we had a national health insurance program in this country, the vaccine could be added to those covered and the problem of lack of funding would be more manageable.

Isn’t it true that the studies were funded by a drug company and so the results are suspect?
It’s true that the studies were funded by Merck itself, but this is standard practice in the drug and vaccine industries. We have advocated that drug companies be required to pay into a pool and that neutral scientists should conduct and analyze drug and vaccine studies. But until this proposal is accepted, most studies of new products will be conducted by their sponsors. While this should always make one skeptical of the results reported, one cannot simply dismiss studies solely on the basis of who is their sponsor. To do so would lead to refusing to take almost all drugs.

This vaccine has been the subject of inappropriate lobbying by the manufacturer. Shouldn’t I mistrust any legislative requirement that may ensue?
We certainly agree that the lobbying for this product has been unseemly. In its greed to maximize profit and its desire to gain a solid foothold before another HPV vaccine is approved, as is expected, Merck opted for the hard sell. It is unusual for a vaccine to be mandated so early in its lifespan. A better course would have been to wait for more safety data to accumulate and then sell the vaccine on its scientific merits, rather than by heavy-handed lobbying.

Doesn’t Public Citizen usually recommend waiting for seven years before using a new product?
We recommend that people wait seven years unless the new product is a breakthrough of some kind.  As there is no vaccine or medication proven to prevent infection with HPV, and because young people often become infected soon after becoming sexually active, we recommend not waiting the seven years in this case.

Will people in the developing world ever have access to the vaccine?
The vast majority of cervical cancer cases occur in the developing world; lack of access to pap smears is a major contributor to the 233,000 annual deaths from this disease. At present, however, there is little evidence that this vaccine will be made available at prices affordable to those in the developing world. This is a tragedy, as it represents a major lost opportunity to save the lives of women worldwide.