The Sidney Hillman Foundation, a New York nonprofit honoring excellence in journalism, announced today that Bob Ortega of the Arizona Republic has won the February Sidney Award for sounding the alarm about a faulty test for HPV, the virus that causes most cervical cancer. Each year, about 12,000 women are diagnosed with cervical cancer and about 4,000 die of the disease.

The SB SurePath test is administered to about three million women each year. The test has an unacceptably high false-negative rate, perhaps as high as 50 percent, compared to less than 10 percent for other tests on market. A false negative means that a woman with HPV is told she’s HPV-free and that she should therefore wait longer before getting tested again. If a patient develops cancer, the delay may make her cancer more difficult to treat.

Ortega’s investigation began when a doctor told him about a patient who was found to have cervical cancer after getting two false-negative SurePath tests in a row.

The manufacturer, Becton, Dickinson and Co., has known about the problem for years, but the FDA only warned medical labs about it last June. Ortega’s investigation found that while labs were clued in, doctors and patients were left in the dark.

Major biomedical labs use Surepath to test for HPV despite warnings about accuracy and even though it is not FDA-approved for this purpose.

“Ortega’s report sounds the alarm about a very important public health issue that potentially affects millions of women,” said Sidney judge Lindsay Beyerstein, “His work raises pressing questions, not just about this particular test, but about how the FDA and medical device manufacturers communicate risk to doctors and the public.”

Bob Ortega is a senior reporter at the Arizona Republic, covering the border. He previously reported for the Wall Street Journal and the Seattle Times, among other publications. He served as a Knight International Journalism Fellow in Paraguay in 1999, and subsequently led media-training projects in Georgia, Ukraine, and Belarus for the International Center for Journalists and IREX through 2005. He is the author of “In Sam We Trust: The Untold Story of Sam Walton and Wal-Mart, the World’s Most Powerful Retailer,” Times Books, 1998.

The Backstory

Lindsay Beyerstein interviewed Bob Ortega about his story:

1. How did you find out that one of the most widely-used HPV tests in American has a high false negative rate?

I was interviewing a pathologist in Pittsburgh last August, on an unrelated story, when he mentioned a patient who’d been diagnosed with cervical cancer after two negative HPV tests in the previous four years. Her tests had used Becton Dickinson’s SurePath test kits. He told me that SurePath was widely used for HPV testing, even though it has FDA approval only for use with Pap tests. This seemed odd to me, so I began digging.

As I looked into this, I found a bulletin that Becton Dickinson and the FDA issued last June warning labs of SurePath’s potential for false-negative HPV tests. That led me to look into how the false-negative rate compares to that of FDA-approved HPV test kits.

2. How often does SurePath yield false-negative results, and how does that rate compare to the false-negative rate for other leading brands?

For the several rival FDA-approved HPV tests, the false-negative rate is under ten percent, according to data from clinical trials. Comparable hard data on SurePath isn’t publicly available. At least three times in the last decade, Becton Dickinson (or its predecessor) withdrew applications for FDA approval to use SurePath for HPV tests. Companies often withdraw applications if a denial seems likely; this allows them to keep the clinical trial data private. However, the limited public data available suggests that SurePath can have a false-negative rate of more than 50 percent.

3. What impact are these extra false-negatives having on women’s health?

Women and their doctors may think they’re free of HPV when they aren’t. That can allow the virus, or the cervical cancer it causes, to become established and harder to treat. I found cases of women who died or had to undergo more invasive treatments, such as a radical hysterectomy, after repeated false-negative results using SurePath.

4. Unlike other leading brands, SurePath is not FDA-approved to test for HPV. Why not?

Legally, a laboratory can use non-FDA approved tests as long as it conducts its own study to establish the test’s accuracy. But by law, the manufacturer can’t give labs guidance on how to use its product for a non-FDA approved purpose. And critics charge that many of these lab validation tests are flawed. Federal laws don’t require the labs to provide their validation studies to the FDA or to any other federal agency.

5. Is SurePath the only widely-used HPV test that isn’t FDA-approved for HPV testing?

Some labs do use other non-FDA approved HPV tests, but none of those tests account for even one percent of the HPV test market. SurePath accounts for one-third of that market.

6. The manufacturer claims that false-negatives don’t become an issue unless the sample is held for at least 8 weeks. How did you go about evaluating that claim, and what did you conclude?

I reviewed 17 independent medical studies relating to SurePath’s use for HPV testing. Many of the studies documented that DNA samples held in SurePath begin degrading within days, in some cases within 24 hours. Because labs often don’t run HPV tests until several days after the sample is taken, this raises an obvious problem.

7. The SurePath kit is typically used for both a Pap smear test (to screen for precancerous and cancerous cervical cells) and an HPV test (to screen for the virus that typically causes these anomalies). Why do some doctors run the Pap test first and wait for the results before running the HPV test?

Gynecologists collect a single sample from which either or both tests can be run. National screening guidelines adopted last year recommend running the Pap and HPV tests at the same time. But earlier guidelines didn’t recommend “co-testing,” as it’s called. Most gynecologists I spoke with said their practice has been to wait for the Pap test results before deciding whether to ask the lab to run the HPV test from the same test-kit sample. That typically results in a four or five-day delay, sometimes more, between collecting a cervical swab and running the HPV test.

8. The FDA and SurePath’s manufacturer sent a warning letter to medical laboratories, but not to doctors or patients. Do you think the FDA has a responsibility to publicize this issue more widely?

Absolutely, yes. More than five months after that warning letter was issued, gynecologists I spoke with across the country, and the two largest national gynecological associations, didn’t know about the bulletin until I told them about it. Most laboratories didn’t pass along the warning; the few that did minimized the importance of it, citing their own validation studies. Most labs I contacted, including LabCorp, the country’s largest chain, declined to say why they use SurePath despite the FDA warning.

9. How long has SurePath’s manufacturer known about this problem?

The manufacturer first applied (and then withdrew its application) for FDA approval to use SurePath for HPV tests in 2002, so there may have been indications of the problem as long as ten years ago. I found independent medical studies published as early as 2006 documenting rapid DNA degradation in SurePath. In any event, people familiar with the FDA applications and with the decision-making that went into the bulletin said both the FDA and Becton Dickinson have known about the issue for years.