FDA approves first cervical cancer-preventing vaccine

July 2006

The FDA approved Merck’s vaccine against human papillomavirus (HPV) to prevent cervical cancer, precancerous genital lesions and genital warts caused by HPV types 6, 11, 16 and 18.

“Clearly, this could make a large impact on women’s health,” John T. Schiller, MD, of the National Cancer Institute of the National Institutes of Health, told Infectious Diseases in Children. “The way to view it is, it can reduce a woman’s chance of getting cervical cancer by 70%.”

The FDA approved the vaccine for use in adolescent girls and women aged 9 to 26 years.

“It appears to be a very promising vaccine that should have a significant impact on the incidence of these four serotypes of HPV,” said Joseph Bocchini, MD, member of the AAP’s Committee on Infectious Diseases. “We think that the best use of this vaccine will be to provide it to all girls and to provide it at an age prior to the onset of sexual activity.”

HPV is the most common sexually transmitted disease in the United States. The CDC estimates that genital HPV infects about 6.2 million Americans every year while more than half of all sexually active men and women become infected at some time in their lives.

On average, there are 9,710 new cases of cervical cancer and 3,700 deaths attributed to HPV in the United States each year. Cervical cancer is the second most common cancer in women worldwide; each year it is estimated that it causes more than 470,000 new cases worldwide and 233,000 deaths.

About the vaccine

Merck’s vaccine is a recombinant vaccine given as three injections over six months. Although the vaccine is expected to prevent most cases of cervical cancer due to the HPV types contained in the vaccine, it will not provide protection for previously infected adolescent girls and women.

The FDA based its approval on four studies of more than 21,000 women aged 16 to 26. Results from the studies showed the vaccine was nearly 100% effective in preventing precancerous cervical lesions, precancerous vaginal and vulvar lesions and genital warts caused by the HPV types contained in the vaccine.

Researchers also performed two studies to measure the immune response to the vaccine among girls aged 9 to 15 years. Their immune response was comparable to the response among women aged 16 to 26. Researchers evaluated safety in a study of about 11,000 participants.

Merck agreed to further study the vaccine post licensure, including general safety and long-term effectiveness. Merck will continue studies to evaluate the vaccine in men and to study the pregnancy outcomes of women who receive Gardasil while unknowingly pregnant.

There is a second HPV vaccine in the pipeline. GlaxoSmithKline expects to file for FDA approval of its candidate HPV types 16 and 18 L1 virus-like particle vaccine with adjuvant AS04 against HPV (Cervarix) before the year’s end.

That vaccine is being evaluated in phase-3 clinical trials that involve more than 30,000 women worldwide. Results from vaccine studies so far demonstrate it has 100% efficacy.

Target the right women

Schiller, one of the codiscoverers of the vaccine, said that in addition to decreasing the odds of developing cervical cancer, in countries with good Pap screening practices the vaccine could reduce precancer Pap screen results by 70%. The HPV types covered by the vaccine cause about 70% of high-grade cervical dysplasias, but only 30% to 40% of low-grade dysplasias.

“One of the important things will be the recommendations by the ACIP [Advisory Committee on Immunization Practices],” Schiller said, “because if they come up with a strong recommendation, chances are the government will help pay for the vaccine for disadvantaged adolescent girls or women. That’s a very important consideration.”

The ACIP put HPV recommendations on its meeting agenda at the end of June.

“Clearly the chance for making a really large impact on human health will depend upon the vaccine getting to disadvantaged women,” Schiller said.

Internationally, he said a reduced-cost vaccine would be important.

“The important thing will be to get the vaccine either bought by benefactors or have the price reduced very significantly so that it can reach poor women around the world who are not getting Pap screening,” Schiller said.

Groups respond

After the FDA’s approval, organizations released statements of support for the vaccine.

“The FDA’s decision marks a historic milestone in the fight against cervical cancer and should be celebrated by women and health advocates around the world,” Susan Crosby, president of Women In Government, said in a release. “The availability of an HPV vaccine brings us one major step closer to our goal of ensuring that no more women die of this preventable disease. For the HPV vaccine to truly achieve its potential, however, it must be available to all recommended age groups, regardless of their socioeconomic status. We urge the federal Advisory Committee on Immunization Practices to assist in this effort.”

Crosby added that Pap screening would still be important. “The HPV vaccine should become a part of comprehensive cervical cancer prevention programs that also use advanced and medically appropriate screening methods, such as HPV testing,” she said.

“Advances in cancer prevention are just as important as advances in cancer treatment,” said Gabriel N. Hortobagyi, MD, president of the American Society of Clinical Oncology.