Coverage concerns The vaccines are likely to be pricey, with estimates ranging between $150 and $500 for the three-dose vaccine; analysts are expecting good coverage. "Cost is going to be a major factor, but you've had more expensive vaccines like Prevnar that have shown good uptake," says Decision Resources analyst John Lebbs. "If you have the clinical justification and the public health issue and rationale—which you do for these vaccines—there's a very good likelihood that the vaccine will be integrated into the [CDC's Advisory Committee on Immunization Practices] immunization schedule." The ACIP is supposed to vote on this in June.

Getting onto the schedule—and obtaining that "universal vaccination" recommendation—is critical. "It means they feel the intervention is important enough for the public health of this country that everyone should get it, and there should be funds available for those children without insurance to get the vaccine," says Barr. "When universal vaccinations are made, uptake is quite a bit more robust because people expend the efforts to make sure the people who need it have access."

One of the convincing arguments for coverage is one based on cost effectiveness. PAP smear screening costs between $4 and $6 billion annually. However, much of that cost can be eliminated—GSK says 40 percent, or $2.4 billion—by using HPV vaccines to prevent the likelihood of abnormal PAP smears in the first place.

THE IMPACT FACTOR

Cervical cancer tends to strike women in their later years because it is so slow growing. And given that Merck and GSK plan to target the 9-15 year-olds, the benefits of vaccination won't be seen for some time. But the industry will see their impact in other areas.

First, Gardasil and Ceravix both rely on, and thus have validated, the use of "virus-like particle" technology, which stimulate immunity to the viruses by mimicking only the surface proteins of the viruses, but don't contain any genetic information. Some say the technology will be applicable for other viral infections with relatively small, simple viruses.

The use of adjuvants is also validated. Says Dubin, "Adjuvant technologies can make a difference. One example, beyond HPV, is a malaria vaccine in development where we have convincing evidence that the reason it appears to be effective is due to the adjuvant being used."

Still others view the introduction of these cancer vaccines in a much broader context, such as helping spark renewed interest in vaccines to treat viral infection or helping lay down needed physician and educational infrastructure that might one day be needed for an AIDS vaccine.

It is for this last point that Barr and Dubin envision more busy nights. "The greatest burden of disease lies in countries with undeveloped medical structures," says Dubin. "The more 'developing' the country, the more cases of cervical cancer. We have been gearing up for this. It requires a huge amount of manufacturing capacity—not to mention working with governments and NGOs, and dealing with the political environment in different countries. These are implementation issues, and where a majority of the challenges for us now lies."

OUT IN FRONT

As per FDA regulations, drug companies must wait until launch to market a product. And PhRMA guidelines advise waiting at least six months after launch to market to consumers. But Digene, a diagnostics company which has had an HPV test on the market since 1999, has already rolled out a glossy consumer advertising campaign to educate women about HPV. "You want to first educate physicians," says Digene's Pamela Rasmussen. "We have a huge amount of data, we're in all the guidelines, we had the thoughtleaders, yet some doctors told us they weren't going to change their habit [and use the HPV test] unless women were asking for it." Rasmussen also said that doctors, surprisingly, were forgoing the test because they didn't feel comfortable educating patients about HPV from scratch. "The DTC ads do a little bit of that job already for the doctors, so women are already aware when they go into the office." It also makes vaccine manufacturers' marketing efforts easier, in that a baseline of knowledge among the public is currently being established.