DNA Test Beats Pap Smear in Cervical Cancer Detection, Study Finds

Oct. 17, 2007— -- Miranda Curlutu remembers the first time she went to the doctor's office for a Pap smear.

"The first time I went, I cried," says Curlutu. "I was so nervous, and the doctor wasn't very comforting about the situation. I actually brought my mom, but … I still cried."

Cervical cancer screening through Pap smears conducted for years during annual pelvic exams have been the standard screening approach for detecting early phases of the disease.

For some women, however, the annual exam may one day become a thing of the past. DNA tests for the cancer-causing human papillomavirus, which are more likely to detect early forms of cancer, could eventually mean less-frequent visits to the doctor for pelvic exams.

But there's a catch. Since these tests are so sensitive, a small number of women may end up getting false positive results, leading to extra tests and unnecessary alarm.

Studies on these new tests were published Wednesday in the New England Journal of Medicine.

The studies -- one Canadian and one Swedish -- found that HPV testing had almost twice the sensitivity of traditional testing, picking up more precancerous lesions than Pap smears do.

And since these tests are so sensitive, the authors speculated that women with negative tests may be able to safely go longer between pelvic exams for cervical cancer screening.

Sensitive Tests Pick Up More Early Cancer

The DNA-based tests for HPV are performed with a pelvic exam, similar to the kind associated with traditional Pap smears.

But instead of the traditional approach of looking for cells showing early signs of cancer, the samples are sent for DNA tests that look for the presence of the human papillomavirus, a sexually transmitted virus that is the cause of most cervical cancers.

In the Canadian study, researchers assigned more than 10,000 women between 30 and 69 years of age to receive either DNA testing for HPV or traditional pap smears. HPV testing was found to be superior for picking up high-grade precancerous lesions, detecting 95 percent of these precursors to cancer, compared with 55 percent for traditional Pap smears.

"When you do screening, what you really want is a very sensitive test -- you don't want to miss any of your cases," explained the lead author of the Canadian study, Dr. Marie-Hélène Mayrand, associate professor of obstetrics and gynecology at the University of Montreal.

"The problem with Pap testing -- on average, it misses about half of the cases of cervical cancers," she said. "In our study, the sensitivity of Pap was 55 percent, but HPV testing had sensitivity of 95 percent; essentially, it almost didn't miss any high-grade lesions."

And in the Swedish study, scientists assigned 12,527 women between 32 and 38 years old to either receive routine care with Pap smears or routine care plus HPV testing. Fifty-one percent more cancers and high-grade precancerous lesions were found in women who initially received HPV testing in addition to pap smears, leading to earlier treatment.

In subsequent screening examinations, this group was later found to have 42 percent fewer cancers or high-grade precancerous lesions.

"The basic result we found is that if you also have a papillomavirus test [in addition to traditional pap smears], you will have a protection against severe lesions the next time you are screened," said lead study author Dr. Joakim Dillner, professor of virology at Lund University in Sweden. "Your risk will be reduced by half the next time."

In addition, the HPV test is sensitive enough that women may be able to go several years between screening appointments.

"We have data from other studies that the protection from a negative HPV test for three to five years is probably about the same as a negative pap smear for one year," added Mayrand. "I am confident that the interval will be able to be lengthened to three or maybe even five years."

More False Alarms

However, DNA testing for HPV was found to have a slightly worse specificity than Pap smears. While the Pap tests only gave false positives 3 percent of the time, the DNA tests yielded a 6 percent false positive rate.

The concern is the additional false positives could force more women to have further medical workup or procedures.

In an accompanying editorial in the New England Journal of Medicine, Dr. Carolyn Runowicz, director of the Neag Comprehensive Cancer Center at the University of Connecticut in Farmington, pointed out, "Improving sensitivity will, by definition, increase the number of false positives and sacrifice specificity."

Mayrand admitted that the DNA test followed this pattern as well. "For any test, specificity and sensitivity go together -- but inversely," she said. "The more sensitive, the less specific."

But she added that the trade-off may be more positive than negative for the women involved.

"The thing that's really interesting is that we found a large gain in sensitivity -- about 40 percent, but only a small drop in specificity -- only 3 percent," she said. "But it is a shortcoming -- we'd all like a perfect test."

Not For Everyone

Before women begin inundating their doctors with questions about the DNA test for HPV, it is important to note that it is not designed to be used by itself for women under 30 -- a time when many women will have asymptomatic infection with HPV.

"In women under 30, HPV infections are frequent," said Mayrand. "Most acquire HPV in the first few years after their sexual debut. But most of those infections will clear on their own and go away. We are happy to not pick those up."

But Dillner thinks that eventually, HPV testing could replace Pap smear testing -- at least for women over 30.

"I think that having HPV as screening instead of Pap is quite likely to happen eventually," Dillner said. "It will be unlikely we screen with just HPV below 30 years of age, but from 35 years and up it is highly likely that we will see at least some countries using HPV screening -- and at quite long intervals."

Maynard agreed. "I would say that in a few years she'll probably be able to have a better test less often; that's the key message," she said. "Instead of a mediocre test every year, let's have a great test every five years."

And patient Curlutu agreed that such a change would be a welcome one.

"It might be nice to go longer between visits," she said. "And given the tradeoff, I think I would like to have the test done -- even if it picks up on something that might not be serious ... I'd rather be safe than sorry."