Cervical cancer can be prevented with early detection by Pap smears and removal of lesions. Still, the cancer kills about 3,700 women in the United States and 250,000 overseas, where Pap smears are less common, making it the No. 2 cancer killer of women worldwide.

The Food and Drug Administration approved Merck's cervical cancer vaccine Gardasil yesterday, inaugurating a vaccine market potentially worth several billion dollars a year, with the Philadelphia area at its core. Gardasil will be manufactured and marketed from Merck's West Point complex. GlaxoSmithKline PLC, developing a rival vaccine Cervarix, has a US headquarters in Philadelphia.

Both vaccines ultimately could save countless lives by helping prevent infection from sexually transmitted strains of human papillomavirus, or HPV, that cause cancer, the FDA and health experts said.

But Merck -- the first to market -- must clear several legal and marketing obstacles before the vaccines will be widely available.

GSK Right Behind Merck

Merck's immediate challenge is persuading federal and state officials to recommend and pay for widespread or mandatory vaccinations, over possible objections of sexual-abstinence and anti-vaccine groups that prefer Pap smears as a proven prevention.

Merck marketers, working already for a year to publicize HPV risks and prime the market, also must take care not to undermine cancer screening and safe-sex campaigns, experts said.

All the while, Merck must watch over its shoulder at GlaxoSmithKline, which hopes to launch Cervarix by late 2007. Its second-to-market strategy is to let Merck pave the regulatory road and then slingshot past Gardasil.

"We congratulate Merck on their launch and we hope to be right behind them," said Brian Lortie, GlaxoSmithKline's vice president for worldwide HPV vaccine development.

Effective Only in Virgins

At stake, beyond public health, is billions in revenue for both companies and a potential economic boost for Montgomery County, home to Merck's vaccine division. With roughly 10,000 employees, it already is Pennsylvania's biggest manufacturer of any kind, state officials say.

Merck, struggling since the 2004 recall of its blockbuster pain pill Vioxx, has staked its turnaround in part on vaccines. They accounted for $1.1 billion of its $22 billion in revenue last year, or 5 percent, the highest share since at least 1995.

About 20 million American women and men carry the HPV virus, transmitted by skin-to-skin genital contact. Condoms don't stop it, according to the Centers for Disease Control and Prevention.

While most HPV infections resolve on their own, a small percentage can cause precancerous lesions and may lead to full-blown cancer of the cervix.

Cervical cancer can be prevented with early detection by Pap smears and removal of lesions. Still, the cancer kills about 3,700 women in the United States and 250,000 overseas, where Pap smears are less common, making it the No. 2 cancer killer of women worldwide.

Merck designed Gardasil to target four HPV strains, two blamed for 70 percent of cancers and two for 90 percent of genital warts -- an extra benefit that Merck's advertising campaigns and sales representatives will push hard, the company has indicated.

GlaxoSmithKline's Cervarix targets the two cancer-causing types and the company is testing for other benefits to differentiate it from Gardasil.

Although both vaccines only work in uninfected girls or women, essentially meaning virgins, Merck and health experts say all should be vaccinated as a preventive measure.

Massive Campaigns Underway

Long before Merck or GlaxoSmithKline had products to sell, both began inundating physicians and women with the message that HPV can cause cancer. Surveys found fewer than 20 percent of people knew about the link, said Beverly Lybrand, vice president and general manager for Gardasil at Merck Vaccines Division.

Merck's corporate "Tell Someone" campaign, launched in April, uses paid TV ads showing actresses, in interview style, expressing surprise about the cause and pledging to tell others.

Last fall, Merck funded "Make the Connection," run by the industry-backed nonprofit Cancer Research and Prevention Foundation and celebrity charity Step Up Women's Network. Designed by the public-relations giant Edelman, the campaign features publicity events, a TV public-service announcement and cameos by celebrities such as Maria Shriver and Jessica Alba wearing girls' beaded bracelets -- designed by Edelman -- to highlight the link.

"That has been very impactful" for girls, Lybrand said.

Neither campaign mentions Gardasil, which Merck could not legally promote until getting its FDA license.

Since last year, Merck has spent at least $1 million on the campaigns without a dime in revenues, including roughly $850,000 on online activities, according to figures from its nonprofit partners and TNS Media Intelligence, a market research firm.

GlaxoSmithKline, so far, has funded one campaign aimed at physicians, called HPVResource.org, Lortie said. It does not mention Cervarix, either.

Health experts applauded the efforts and marketers called them a sign of the high stakes. Wall Street analysts have pegged sales of Gardasil alone, at $360 for a three-shot dose, at between $1 billion and $3 billion by 2010. Merck shares barely budged yesterday on the FDA news, closing at $33.97, up 1 cent.

"Starting early is a key to success," said Paul L. Rosenberg, a vaccine development expert and partner at Bain & Co., a Boston-based consulting firm.

Opponents Raise Objections

Merck's campaign emphasizes that the best protection, in addition to the vaccine, is abstaining from sex or staying in long-term, monogamous relationships and getting regular Pap smears.

Those were key issues for Christian groups concerned the vaccines would increase promiscuity by liberating girls from fear of infection. After Merck and GlaxoSmithKline proved their vaccines could save lives, the groups embraced the vaccines but demanded the companies don't portray them as a panacea nor try to make them mandatory for school enrollment.

"Parents have an inherent right to be the primary educator and decision-maker regarding their children's health," the Family Research Council said in statement in response to questions.

At least one other group, the nonprofit National Vaccine Information Center, opposes Gardasil and Cervarix as unnecessary with unknown safety risks.

Merck will try to hurdle those concerns starting June 29, when immunization experts at the CDC meet to consider adding Gardasil to their list of recommended vaccines. If they do so, as expected, Congress will vote on supplying Gardasil to immunization programs, private insurers will consider paying for it, and state health officials will weigh requiring it for enrollment.

Lybrand, who said insurers appear ready to pay for Gardasil, said Merck will "support" state officials in deciding to make Gardasil mandatory and already has contacted most of them. GlaxoSmithKline's Lortie said his company also "will put effort in that direction."

At least one state official, Alice Gray, immunization program director at the Pennsylvania Health Department, welcomed the companies' input but insisted it won't influence her. "None of the manufacturers make decisions for us on whether we require it," Gray said.

There is one precedent: the vaccine against Hepatitis B, also sexually transmitted, is mandated by most states. Some critics urge letting parents "opt out" for personal reasons.

How Merck's path-clearing work will affect GlaxoSmithKline's Cervarix is unclear. Some health-care experts and equity analysts said they expect the winning vaccine, ultimately, will be the cheaper one, possibly meaning less-than-projected revenues for both.