F.D.A. panel recommends replacement for the Pap test

MARCH 12, 2014

The Pap test, a ritual for women that has been the mainstay of cervical cancer prevention for 60 years, may be about to play a less crucial role.

A federal advisory committee recommended unanimously on Wednesday that a DNA test developed by Roche be approved for use as a primary screening tool.

“Has our Pap, as we know it, outlived its time?” Dr. Dorothy Rosenthal, a professor at Johns Hopkins University, testified to the committee, which advises the Food and Drug Administration. She said deaths from cervical cancer in the United States had stopped declining and that there would be “a tremendous gain” by moving to the new test.

The Roche test detects the DNA of human papillomavirus, or HPV, which causes almost all cases of cervical cancer. Pap testing involves examining a cervical sample under the microscope looking for abnormalities.

Until now HPV testing has been used mainly as a follow-up test when the Pap results were ambiguous, or used jointly with Pap testing.

Wednesday’s 13-to-0 vote — by a committee mainly of academic pathologists, microbiologists and gynecologists — would allow Roche’s test to be used alone as the initial test for women 25 and older.

The Roche test is seen as better than Pap tests in finding precancerous lesions.

The Pap test, which is well entrenched and has been highly successful, will not go away quickly, if at all, however.

Assuming the F.D.A. itself agrees with its advisory committee and approves the new use of Roche’s test, it would become just another option, not a replacement for the older testing regimens. And many doctors will not adopt the new test unless professional societies recommend it in guidelines, which could take years.

Use as a primary screening tool could mean much wider sales of HPV tests. The United States market for such tests is more than $200 million, according to DeciBio, a market research firm.

Qiagen is the leading seller of such tests, with Roche and Hologic and BD also participating. Various laboratories also offer their own tests. But the approval as a primary screening tool would be only for Roche’s Cobas test, which could help it gain market share.

Current United States guidelines recommend that women 30 to 65 undergo either co-testing with both HPV and Pap every five years, or Pap testing alone every three years. Women 21 to 30 are supposed to have Pap testing every three years.

The American Cancer Society estimates that about 12,360 new cases of invasive cervical cancer will be diagnosed in 2014 and about 4,020 women will die from the disease. Between 1955 and 1992, the cervical cancer death rate declined by almost 70 percent, mainly because of Pap testing. The death rate has remained stable in recent years.

HPV testing has advantages over the Pap test. Studies have shown it is much more sensitive in detecting precancerous lesions. Proponents say it is more objective, its results varying less from lab to lab than those of the Pap tests, which rely on the judgments of people viewing slides under a microscope.

The main drawback of HPV testing is that most people get infected with the virus after they become sexually active, although in most cases their immune systems can clear the virus. So many women, particularly young women, would be sent for additional examinations or biopsies that might not be necessary. That is why co-testing with both HPV and Pap is recommended only for women 30 and over.

Roche says it sidesteps that problem because its test specifically detects two subtypes of the virus, known as genotypes 16 and 18, that account for 70 percent of the cancer cases.

In its study, Roche showed that its test outperformed Pap testing alone in various measures, like the ability to detect precancerous lesions. A negative result on the HPV test was also a better predictor than a negative Pap test that a woman would remain free of lesions for the next three years.

Most people who testified to the committee, which met in College Park, Md., urged approval, some saying it was time to move to modern molecular science.

“George Papanicolaou did not know about HPV,” said Lee Shulman, a professor at Northwestern University, referring to the initial developer of the Pap test. He compared replacing Pap smears with HPV testing to the transition from the horse to the automobile.

But there were objectors who said the data was not sufficient to justify such a change.

“The proposed indication represents a radical shift in clinical practice which would affect millions of women for most of their adult lives,” said Anna E. Mazzucco of the Cancer Prevention and Treatment Fund, a patient support and advocacy group.

She said that most cases of cervical cancer were in women who did not undergo screening, not in those whose disease was missed by screening.

While the committee vote was unanimous, some members had reservations about using HPV testing for women under 30. Some said that HPV testing may not be much better, if at all, than the currently recommended use of both tests.

“I think women are going to be well served by having more choices, but it’s going to be very interesting to watch over the next several years as this rolls out,” said Dr. Alan G. Waxman, a professor of obstetrics and gynecology at the University of New Mexico.