Is Your HPV Test FDA Approved?

bd sure pathSome doctors and their patients will be surprised to learn that the test they are using to screen for HPV may not be FDA approved, according to a special investigation by the Arizona Republic/USA Today.

HPV Testing can be performed on the same specimen as the pap smear, often after the pap result is found to be mildly abnormal, in a process called HPV co-testing.

But if your pap smear has been obtained using Becton Dickinson’s Sure -Path pap collection system, you and your doctor need to know that the specimen it is not FDA approved for HPV co-testing, due to higher than acceptable false negative HPV results resulting from specimen degradation in the SurePath media over time.

This has not stopped some of the nations largest labs, including Quest Dignostics, Lab Corp, Aurora Diagnostics, Sonic Health, Bio-Reference Labs and ARUP labs, from using the Sure-pap specimen off label for HPV co-testing, based on studies each lab has done to confirm the validity of the test in their hands. Although such off-label use is perfectly legal, the FDA and the manufacturer issued a letter in June warning the labs that they should be using an FDA-approved system test and not the SurePath for HPV testing.


That letter, however, was only sent to the laboratories and not to the doctors using the Sure Path system, meaning that physicians and their patients were unaware of the issue until it was reported this week in the press.

You should know that the BD specimen is just fine for the pap testing itself, comparing favorably to its competitor, the Thin Prep System, and perhaps having lower rates of unsatisfactory specimens than Thin Prep. SurePath is also FDA-approved for co-testing for gonorrhea and chlamydia. But not HPV co-testing.

How big is the potential problem?

Just how high the false negative rate is with SurePath is not clear – since the FDA applications for HPV co-testing with SurePath were withdrawn, the data are nowhere in the public domain. The Republic article tries to estimate the potential impact, but they do not cite the study they are using to make their estimates, so I quote this with some reservation update – see reference in comments –

SurePath accounts for about a third of the HPV tests, or about 3 million a year, estimated Michael Farmer, a market analyst who specializes in the pathology and histology laboratory markets. … extrapolating from the findings of a Johns Hopkins University study (unfortunately, not cited – MMP) suggests a thousand or more women tested each year using SurePath may be told they are HPV-free when they are not.

Why would a lab use a non-fda approved test over one that is approved?

Most leading national labs would not explain to The Republic why they use SurePath despite the warning. But each kit costs labs between $1 and $2 less than alternatives that are FDA-approved for HPV tests.

Both Quest and ARUP labs reported doing their own internal validation before using the SurePath for HPV testing, and Quest’s validation included patient samples, as if they were running their own little FDA trial. BIo Reference Labs states they switched 90% of their clients to an fda-approved test when they got the warning from the FDA. ARUP apparently sent letters to clients in October notifying them of the FDA’s warning.

There appears to be support in the pathology community for using the SurePath system for HPV testing, since the College of American Pathologists states the following  –

Non-FDA approved off-label methods for hrHPV DNA detection are commonly used in laboratories, and are acceptable under CLIA ’88 assuming appropriate self-validation studies are performed. Such off-label use most commonly consists of approved methods (Qiagen or Hologic) used with different non-FDA approved transport medias ( e.g., BD SurePath). In addition, non-FDA approved methods such as polymerase chain reaction (PCR) and in situ hybridization have been used for high risk HPV DNA detection. Because of the high volume of hrHPV testing performed and the implications for clinical management of patients based on the results, guidelines for validations have recently been published and include both analytic and clinical components.

However, Phil Castle, PhD, a cervical cancer researcher who was interviewed for the article, had this to say in his blog about using the BD pap for HPV testing –

Currently, there are 4 FDA-approved HPV tests for cervical cancer screening. However, none of them have approval for use with a liquid-based cytology (Pap) buffer called SurePath. Many pathologists like SurePath for Pap testing. But there is no approval for HPV testing because the buffer degrades the quality of the HPV DNA very quickly. A manufacturer of one FDA-approved HPV test has failed to get FDA approval for use of SurePath several times. Even the company that makes SurePath, BD, is urging clinical labs to stop this practice.

What is disconcerting is that there are plenty of alternative choices for valid HPV testing. So it is unethical to offer women less than optimal care just because a pathologist wants to use SurePath.

I myself would not be satisfied with a lab’s internal validation of a non-FDA approved test when an FDA-approved alternative exists. I had always assumed (naively it seems), that any test a lab uses must be FDA approved. If not, then the result I receive from that lab should indicate to me what test they are using, why it is being used and what issues exist with that test.

I do not use the BD Pap Collection Kit

My patients can be assured that the pap collection system I use in my office (Thin Prep) is FDA approved for both Pap and HPV co-testing.

What should you do with this information?

Ask your doctor what Pap smear collection kit he/she uses – it will be prominently labelled on the collection vial for you to see. If it’s BD’s test, and you need HVP testing, make sure a separate specimen for HPV is taken using an FDA-approved collection device.

If you’ve had a recent negative HPV test, ask your doctor how the specimen was obtained. If it was done using the BD pap system, ask your doctor if there is a need for repeating the test using an FDA-approved collection device. If your doctor thinks it is prudent, then retest. In most cases, so long as your pap was normal, simply doing a pap and repeating the HPV at your next checkup will be all that is needed. If the negative HPV was used, however, to triage an mildly abnormal pap, then a sooner repeat pap or repeat HPV test might be indicated.

Logistically, not being able to to an HPV on the pap vial is problematic, since we often do not know until after the pap is read whether or not HPV testing is needed.  By default, then, docs may end up either moving to another pap system or getting HPV routinely with every pap using an FDA-approved collecting system.

Kudos to Bob Ortega at the Arizona Republic for some of the best health reporting I have ever seen.

His article not only gives me almost everything I need to know on this issue as a clinician, but includes information on how the article was complied, and excellent info for patients wondering what to do themselves with this information. Unfortunately, however, he did not link to the Hopkins study that he cited, and I’ve been unable to find the study myself. UPDATE – see reference in comments. Thanks, Dr Austin!


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6 Responses to Is Your HPV Test FDA Approved?

  1. The Hopkins study is Am J Clin Pathol 2012; 138: 223-229. Only 1 of 8 (12%) cancer cases and only 84% of HSIL cases tested Hybrid Capture 2 HPV+ from the SurePath vial, both less than a widely cited 90% standard.

    • If HPV tests are used to screen for cervical cancer and HSIL cases, “a widely cited 90% standard” is not sensitive enough. According to a WHO report published in J Clin Microbiol 2012; 50:2289-98, none of the currently FDA-approved HPV test kits are proficient. Many excellent diagnostic test procedures were used as laboratory-developed-tests by pathologists working at the bench before device manufacturers brought them to the attention of the FDA.

  2. Qiagen is aware of the issue of formaldehyde induced cross linking having an affect on the HC2 HPV test. They also requested the use of proteinase K be included in the sample preparation before the extraction process to overcome this problem. When the testing is done correctly on SurePath collections, HC2 provides reliable results. There are many laboratories that have self validated the method with the proteinase K step in the procedure. Roche cobas4800 has approved SurePath for their HPV assay in Canada.

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