HPV Vaccine Flags Need for More Pap Tests

A little more than a year ago, the nation's first vaccine against some human papillomavirus (HPV) infections was released.

This medical progress against cervical cancer got swept up by fear-based marketing that helped to generate premature calls for government mandates.

"You could become one less life affected by cervical cancer" is the mantra in most of Merck's ads for its vaccine, called Gardasil. The ubiquitous marketing campaign may leave viewers thinking that cervical cancer is more prevalent than it really is.

Merck also lobbied behind the scenes to make its vaccine mandatory for school-age girls, quietly funding groups such as Women in Government that promoted mandatory vaccination bills in state legislatures. Such a mandate, if passed quickly, would have increased the firm's sales before a competitor's product -- soon to hit the market -- was available.

When Merck's funding was exposed, the tactic backfired, fanning suspicions that profit motives were overwhelming public health concerns.

Opposition came from other camps too. Some parents pointed to the new vaccine's side effects (which are usually minor and transient) and questioned whether it should be required. Social conservatives raised concern that the vaccine could lead to increased sexual activity among America's youth.

HPV vaccination has been approved for females ages 9 through 26 and appears to be most beneficial for girls with no prior sexual activity. Studies show that vaccination after virus exposure is only minimally effective. The vaccine is not recommended for pregnant women, anyone with moderate to severe acute illnesses or anyone with sensitivity to vaccine components.

All of this has left a number of questions simmering.

Would a Mandate Reduce Cervical Cancer?

The U.S. Centers for Disease Control and Prevention predict a 22 percent to 60 percent reduction in cervical cancer attributable to this vaccine. However, for these reductions to be realized, a high proportion of young women will have to be vaccinated. Even then, reductions in invasive cervical cancer won't be measurable for several decades.

Many believe mandates are premature. Gardasil appears safe and effective up to five years, the length of time studies have covered so far, and if its effects are as strong over the long term as early results suggest, then requiring and funding vaccination for school-age girls (with exceptions for families who opt out) may become the best way to ensure access and protection for all girls, regardless of class or race.

About 10,000 cases of cervical cancer will be diagnosed this year in the United States, and about 3,700 of these women will die from the disease.

Most who die of cervical cancer never had regular Pap tests. These screening tests can detect pre-cancerous tissue, which can be removed to prevent the development of cervical cancer.

In the United States, there are 6.6 cases of cervical cancer for every 100,000 white women and 10.5 cases for every 100,000 African American women. The racial disparity is due at least in part to women of color having less access to screening.

Globally, in regions where screening is much less common, the numbers are much worse. In areas of Africa, Central and South America, and Micronesia, there are more than 50 cases of cervical cancer per 100,000 women.

We don't know yet if requiring vaccination could reduce cervical cancer deaths and reduce racial and ethnic disparities in terms of HPV prevalence, cervical cancer incidence and cancer mortality. It is possible that women who do not get regular Pap screening and follow-up now will also be those least likely to be vaccinated, even with legislative mandates in place.

If there's one thing the discussions make clear, it's that we need to try harder on Pap tests. Cervical cancer used to be a leading cause of cancer deaths among U.S. women. But since the introduction of the Pap smear in the 1940s, those deaths have dropped about 75 percent, even as the population has grown.

What Does the HPV Vaccine Achieve?

HPV is the most common sexually transmitted infection in the United States, affecting about 1 in 4 women between 14 and 59. Exposure usually occurs within the first few years of sexual activity, but infections often go unrecognized because there may be no symptoms. The vast majority of HPV infections clear up on their own.

Worldwide, 70 percent of women who develop cervical cancer have been infected with either HPV 16 or HPV 18, two of the strains the Gardasil vaccine targets. But most women infected with even such "high-risk" strains of HPV will not develop cervical cancer.

In addition to effectively protecting against HPV 16 and HPV 18, Gardasil protects against types 6 and 11, two strains that can cause genital warts but not cervical cancer.

Cervarix, a vaccine that GlaxoSmithKline expects to introduce in the United States soon, also protects against HPV types 16 and 18, but not the strains that can cause genital warts. Both Gardasil and Cervarix may provide partial cross-protection against some additional HPV types.

Neither vaccine protects against all strains of HPV that can lead to cervical cancer. In addition, testing of Gardasil has shown that it is far less effective if women have been exposed to HPV before vaccination. This is one reason why vaccination of girls as young as 9 has been recommended.

Regular Pap tests and follow-up care are still needed, even for women who are vaccinated, because they may have prior exposure to HPV or may in the future become exposed to strains that are not covered by the vaccine.

It is worth noting that HPV vaccine trials have demonstrated only protection against HPV-related genital pre-cancers, not cancer.

Should HPV Vaccines Be Made Available to All?

Is spending public money on HPV vaccination of all girls and young women appropriate, when cash-strapped communities could put the funds to other uses? This may be the most difficult question of all.

It leads immediately to another question: Does Merck need to charge $360 per person for the vaccine as it does now? According to Glenn McGee of Albany Medical College, Merck could recoup in several years its development costs for this and other vaccines that never made it to market by charging one-tenth the current price (assuming that sales continue at the current rate).

Merck says it calculated the price taking into account research and development costs as well as what the vaccine could save in terms of HPV-related treatment expenses. It argues that the long-term cost savings justify the unusually high price for this vaccine. Other analyses (for example, a British Columbia Cancer Agency report) disagree with these calculations and conclude that the cost of vaccination greatly outweighs the amount saved by avoiding treatment of HPV-related disease.

As we consider how to proceed on HPV vaccination, a clear understanding of the research -- not marketing claims or lobbying funds -- needs to guide both our individual decisions and our public policy.