Cervical cancer vaccine highly promising, but questions remain

Many experts recommend vaccinating all preteen girls. Others urge caution.

In 2006, the FDA approved Gardasil, the first vaccine designed to prevent infection with the human papillomavirus (HPV). There are more than 100 strains of HPV, and 30 to 40 are sexually transmitted. Gardasil, made by the drug company Merck, targets strains 16 and 18, which are implicated in 70% of cervical cancers, and strains 6 and 11, which cause 90% of genital warts. The vaccine was approved on the basis of early results showing that it was virtually 100% effective in preventing infection by the targeted strains for up to 18 months.

Given as a series of three shots over six months, Gardasil is licensed for use in girls and young women, ages 9 to 26. It works best if it's given before the start of sexual activity and potential exposure to HPV. Since its approval, the Advisory Committee on Immunization Practices — an arm of the Centers for Disease Control and Prevention (CDC) — has recommended routine vaccination of 11- and 12-year-old girls (and girls as young as age 9, at their clinicians' discretion). The CDC also recommends that Gardasil be offered to older girls and young women on the assumption that even if they've been exposed to HPV, they may not have encountered the particular strains contained in the vaccine.

This vaccine could save thousands of lives and has major implications for the future of cancer prevention. The need for it might seem less pressing in this country, where Pap test screening to detect precancerous changes in cervical cells is part of regular gynecological care. Cervical cancer rates in the United States have fallen by 50% since the 1970s. Still, nearly 10,000 American women were diagnosed with cervical cancer in 2006, and about 4,000 died from it. In developing countries, where Pap test screening isn't yet in place, cervical cancer is far more common and often lethal. Worldwide, more than 250,000 women die each year from the disease.

Clinicians and public health officials are understandably enthusiastic about the HPV vaccine, but it's not a magic bullet. Gardasil is not effective against the HPV strains believed to be responsible for nearly one-third of cervical cancers. Neither is GlaxoSmithKline's Cervarix, which is not yet approved. Meanwhile, a political controversy is building. Several states have proposed mandating HPV vaccination for young girls, but this idea is encountering resistance. Some parents and others contend that the decision about whether to vaccinate a girl against a sexually transmitted disease is best left to her family, in consultation with her pediatrician or family physician. There is also opposition to mandatory vaccination based on concern about unknown risks. To answer some of these concerns, Merck is continuing to follow participants in the clinical trials that led to Gardasil's approval in June 2006.

The latest findings — representing three additional years of follow-up involving 17,500 women, ages 15 to 26, in several developed and developing countries — were published in the May 10, 2007, issue of the New England Journal of Medicine. In one study, Gardasil was found to be 98% effective in preventing precancerous and cancerous cervical lesions associated with HPV types 16 and 18 in women who hadn't already been infected with those strains. In a second study, the vaccine was 100% effective in preventing genital warts and precancerous and cancerous lesions of the vulva, vagina, and cervix in women who were not infected with any of the four targeted strains at the time of vaccination. But in women who had prior infection — with the targeted HPV strains, other strains that cause genital HPV infections, or both — the rate of lesions was reduced by only 17% in the first study and less than 35% in the second.

These results confirm that as long as the vaccine is given before a girl or woman has been infected with one of the four targeted strains of HPV, it does an excellent job of preventing genital warts and lesions of the cervix, vulva, and vagina caused by those strains. However, the vaccine's effectiveness clearly diminishes once sexual activity begins.

The studies also have some limitations. Although the vaccine appears to be safe for up to five years after it is given (the most common side effects are pain at the injection site and fever), both its safety and its effectiveness are unknown beyond that point. In addition, the follow-up trials did not enroll anyone younger than age 15, so there's only limited information on the vaccine's safety and effectiveness in girls ages 11 and 12 — the age at which health authorities are saying girls should be vaccinated.

Finally, it will be a long time before we know how much protection from cervical cancer the vaccine will provide. One concern is that immunity to the targeted strains will lead to increased prevalence of other cancer-related HPV types that are now less common. A study of HPV infection in the United States found that although 25% of 14- to 19-year-olds and 45% of 20- to 24-year-olds were infected with HPV, only 3.4% were carrying the particular strains targeted by Gardasil and the yet-to-be-approved Cervarix (Journal of the American Medical Association, Feb. 28, 2007).

This vaccine is a major scientific and medical achievement. Researchers have harnessed the immune system to prevent certain strains of a cancer-causing virus from getting a foothold. It works safely and remarkably well for up to five years in young women without prior infection. But there is reason to be cautious. The benefits and risks of the HPV vaccine aren't fully known, especially in the preteen girls for whom vaccination has been strongly recommended. Also, the need may be less urgent in women who receive regular Pap test screening (reducing their risk for invasive cervical cancer) and practice safe sex (reducing their risk for HPV infection). Certainly the HPV vaccine shows great promise. Nevertheless, given the many unanswered questions about its effectiveness and safety in different populations of girls and women, its use should be more a matter of individual choice than government mandate.

Women's Health Watch
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