• 10/21/2007
  • Montreal, Quebec, Canada
  • Michael Smith, Senior Staff Writer, MedPage Today
  • MedPageToday.com

Viral testing to detect cervical cancer appears to outperform the conventional Pap smear in some respects, researchers here have concluded.

In a randomized trial, a test for the human papillomavirus was significantly more likely (P=0.01) to identify cases of cervical intraepithelial neoplasia (CIN) than a Pap smear, found Marie-Hélène Mayrand, M.D., of McGill University, and colleagues.

On the other hand, the viral test was significantly more likely (P<0.001) to identify a healthy woman as having CIN, the researchers reported in the Oct. 18 issue of the New England Journal of Medicine.

The Canadian study is one of two in the journal comparing testing for HPV with the conventional Pap test.

In the other, Swedish scientists showed that a viral test appears to detect pre-cancerous and cancerous lesions earlier than the Pap test. The study comes just a few weeks after a study in Holland produced similar results. (See: DNA Tests for HPV Improve Cervical Cancer Screening)

But the findings don’t mean that viral tests are ready for “prime time,” said Carolyn Runowicz, M.D., of the University of Connecticut. Dr. Runowicz, who wrote an accompanying editorial in the journal, said the results are “exciting” but preliminary.

Among other things, she said, their application to U.S. practice is limited: Both studies used a slide-based Pap test, while 85% of tests done in the U.S. use liquid-based cytology, and the Swedish study used a highly sensitive viral test that is not available commercially.

A study now underway in 25,000 women — dubbed A Randomized Trial in Screening to Improve Cytology, or ARTISTIC — is comparing viral tests to liquid-based cytology, but results are not available yet.

The current studies show that molecular screening is both possible and promising, she said, and may reach the clinic if performance can be improved and cost can be reduced.

“We’re not there yet,” Dr. Runowicz said.

Between Sept. 26, 2002 and Feb. 3, 2005, the Canadian researchers randomly assigned 10,154 women, ages 30 to 69, to one of two groups — a “focus on Pap” group, which got a Pap smear followed by the viral test, and a “focus on HPV” group, which got the HPV test first, followed by a Pap smear.

For ethical reasons, all women got both tests, which were performed at the same session, but the design allowed the researchers to compare the two tests head to head, Dr. Mayrand and colleagues said.

The researchers found that the viral test — commercially available and approved by the FDA — correctly identified cervical intraepithelial neoplasia of grade two or three 94.6% of the time, compared to 55.4% for the Pap test.

On the other hand, the specificity of the viral test was 94.1%, compared to 96.8% for Pap testing, they found.

From May 1997 through November 2000, the Swedish researchers randomly assigned 12,527 women ages 32 to 38 to get a Pap test (and form a control group) or a Pap test combined with a test for human papillomavirus using polymerase chain reaction.

They calculated rates of CIN2, CIN3, and cervical cancer at baseline and at subsequent screenings, according to Pontus Naucler, M.D., Ph.D., of Lund University in Malmo, and colleagues.

At baseline, the study found, the proportion of women in the two-test group who had CIN2, CIN3, or cancer was 51% higher than among the women who only got the Pap test.

But at the subsequent screening, following treatment where appropriate, the rate in the two-test group was 42% lower than in the control group.

Some of the differences might have been the result of over-diagnosis at baseline, the researchers said, but not all. “The improved sensitivity of HPV testing is not merely due to over-diagnosis but is attributable, at least in part, to earlier diagnosis of lesions that do not regress,” they concluded.

Notes:
1. The Canadian study was supported by the Canadian Institutes of Health Research and Merck Frosst Canada. Dr. Mayrand reported receiving consulting and lecture fees from Merck Frosst, Pfizer, Roche, and GlaxoSmithKline. Other authors also reported financial links to a range of industrial organizations.

2. The Swedish study was supported by the Swedish Cancer Society and Europe against Cancer. The researchers reported no potential conflicts.