Harvard Health Letter

The cervical cancer vaccine

A new vaccine promises to save lives, but won't replace the Pap test.

Cervical cancer once killed many American women — mothers, daughters, and wives. But over the past 30 years, the number of cervical cancer deaths in the United States has dropped by half. Today, fewer than 4,000 American women die each year from the disease.

The main reason for the decrease is the Papanicolou test, or "Pap smear," which is perhaps the most effective cancer-screening test we have. During a pelvic examination, the doctor uses a small brush to gently swipe the surface of the cervix, the necklike part of the uterus that connects to the vagina. The sample is then smeared — thus the nickname — onto a slide so it can be examined under a microscope to check for abnormal cervical cells that are cancerous or might become so. Under current guidelines, women should start getting regular Pap tests within three years after first having sexual intercourse, or at age 21, whichever comes first. Before their 30th birthdays, they're supposed to have the test every year — thereafter, just every two to three years, as long as they've had three normal tests in a row.

But now cervical cancer prevention is entering a new era. The FDA has approved a vaccine against the human papillomavirus (HPV), the virus that's believed to cause almost all cases of cervical cancer.

It's a remarkable achievement: The viral origins of a serious cancer have been identified, and researchers have successfully harnessed the immune system to prevent it. But it's also controversial because 11- and 12-year-old girls are prime candidates for receiving the shots, and some conservative groups fear the vaccination will send a message that it's okay for preteens to be sexually active.

HPV mingles with our DNA

Researchers discovered in 1986 that several strains of HPV cause cervical cancer. HPV is the most common sexually transmitted viral disease in the world, and experts estimate that at least half of all sexually active people will be infected by it at some time in their lives.

There are about 100 different strains of the virus, but only 30 are associated with cervical cancer, and just two, strains 16 and 18, are responsible for about 70% of all cases. Most of the time, people are able to clear the infection, but when HPV successfully evades the immune system and persists in cells, cancerous changes can occur. HPV can mix its DNA with ours, turning off tumor suppressor genes in the process. These genes are essential in controlling the number of times a cell divides and reproduces itself. With the brakes off, uncontrolled cell growth — cancer — occurs. Fortunately, it can take decades for the cancer to develop. That's one reason why regular Pap tests work: There's ample opportunity to detect abnormal cell growth before it turns into full-fledged cancer.

Vaccine made of selected proteins

Scientists at the National Institutes of Health (NIH) developed the HPV vaccine. The vaccine does not contain the killed or weakened virus, as do many vaccines. Instead, it uses just some of the virus's important proteins. The immune system's response to the proteins is enough to stop the virus from infecting the cells of the cervix.

Merck and GlaxoSmithKline have developed the vaccine for commercial use. The FDA approved Merck's version in June. GlaxoSmithKline's is still in clinical trials.

The Merck vaccine targets HPV strains 6 and 11, which cause 90% of genital warts — warts that grow in the genital areas of men and women — as well as the major cervical cancer–causing strains, 16 and 18. Given as a set of three shots over six months, the vaccine will protect against only those four strains. And it isn't therapeutic, which means that if there is an existing infection, the vaccine doesn't bring much to the fight.

CDC recommendations

The Centers for Disease Control and Prevention (CDC) added the HPV vaccine to its official vaccination recommendations in July. It proposed that all 11- and 12-year-old American girls get the shots, although girls as young as 9 could receive it if they're sexually active. For "catch-up," the CDC also recommended that girls and women ages 13–26 be vaccinated against HPV, regardless of their Pap test results.

The reason the CDC recommends vaccinating preteens is that the vaccine works best before an individual has been exposed to HPV. From a public health standpoint, early vaccination stands the greatest chance of making a dent in cervical cancer incidence.

Older girls and young women were included in the recommendations because even if they've had some exposure to HPV, it may not be to the strains contained in the vaccine, so they'll get some protection.

More studies are needed before recommendations can be made for women older than 26 and for males. Obviously men can't get cervical cancer, but vaccinating males might curb HPV transmission and protect them from HPV-related genital and anal cancers.

Note that the CDC only makes recommendations. It's up to individual states to decide, for example, if the HPV vaccine will be required for school entry.

Conservative objections

Emergency contraception and condom availability programs have also been criticized by conservative groups for promoting risky sexual behaviors. So far, studies have shown they don't have that effect. Researchers have found that many factors influence an individual's decision whether or not to have sex, with fear of contracting a sexually transmitted disease being just one of them.

Will Pap tests still be needed?

Cost-effectiveness studies have found that with the HPV vaccine, Pap test screening could begin at age 24 and be done less often. Yet partly because of the Pap test, generations of women have gotten into the habit of seeing a doctor regularly. If the Pap test becomes less routine, the HPV vaccine might have the unintended effect of eroding women's ties to their doctors. On the other hand, doctors or other health care providers might use the HPV immunization visits as an opportunity to broach sexual and other health issues with preteens.

For now, though, Pap test screening is still essential. The new vaccines don't include HPV strains believed to be responsible for about 30% of cervical cancers. Regular Pap tests will still be the best way to prevent cancers caused by those strains. Besides, we'll need more experience, and perhaps some clinical trials in places where cervical cancer is common, before we can be certain that HPV vaccination, in actual practice, lowers cervical cancer incidence. Till then, Pap test screening will remain an important safeguard.

Saving lives in the developing world

Cervical cancer screening and treatment is well developed in the United States, so the gains here from HPV vaccination, while worthwhile, may be modest. The vaccine may make a bigger difference in poor countries. Worldwide, cervical cancer remains the second most lethal cancer for women, with the toll much greater in the developing world.

Price, however, is a major hurdle. In the United States, Merck's retail price for the full series is $360. Several groups are negotiating with Merck and other companies to get the vaccine at a lower price. We've posted information about these admirable efforts on our Web site at www.health.harvard.edu/healthextra.