CEO SUMMARY: With patience and persistence, Digene, Inc. is developing the effectiveness of its DNA-based HPV assay. Publication of recently-completed clinical trials provides evidence that Digene’s Hybrid Capture II ® HPV test, with further improvement, might become a relevant tool in the diagnostic pathway for cervical cancer. It’s another new technology with the potential to change how Pap smear testing is conducted.
EXPECT THE PAP SMEAR technology wars to heat up shortly. The new competitor is Digene, Inc., based in Gaithersburg, Maryland.
Digene joins Cytyc Corporation and TriPath Imaging, Inc. in the battle to replace the traditional Pap smear. Each company is developing a different technology it hopes will demonstrate superior performance in clinical use over the traditional Pap smear.
In the case of Cytyc and TriPath Imaging, each company offers products which change the way a Pap smear specimen is prepared and/or screened. Digene, in contrast, offers its Hybrid Capture II® HPV Test as a blood-based test to determine whether human papillomavirus (HPV) is present.
Pap Smear Technology War
This Pap smear technology war represents two important developments in the clinical laboratory industry. First, there will be a huge impact on the economics of laboratory medicine should any or all of these competing new technologies achieve clinical acceptance. After all, approximately 55 million Pap smears are currently performed yearly just in the United States. Any change away from traditional Pap testing would be a huge shift in lab practices.
Second, the struggle to introduce enhanced Pap smear technology provides an opportunity to learn how the new, cost-driven managed care marketplace evaluates, accepts, and implements new medical technology.
As THE DARK REPORT has noted in past years, the struggles of Pap smear innovators demonstrate how difficult it is to introduce new technology in today’s healthcare market. Regulators, clinicians, and payers no longer automatically accept new technology for widespread clinical use that may be more expensive and only marginally better than current clinical practices.
Efforts by Cytyc and TriPath Imaging (formed from the merger of AutoCyte, Inc. and NeoPath, Inc.) to introduce their thin layer Pap smear preparation and automated screening technologies have been well-chronicled by THE DARK REPORT since the companies earned FDA approval in the mid-1990s.
The new player on the scene is Digene. Its HPV test uses blood, not cervical cells, to detect the presence of HPV. Clinical trials indicate a high correlation between cervical cancer and the presence of HPV.
HPV/Cervical Cancer Link?
Some researchers believe that clinical studies now point to HPV as a cause of cervical cancer. The Kaiser Family Foundation held a briefing for journalists on February 17. The briefing show-cased a number of physicians and researchers who publicly declared that “HPV testing is a more effective screening method for cervical cancer than the traditional Pap smear.”
Just two weeks ago, on March 17, researchers involved in the National Cancer Institute’s (NCI) ALTS (ASCUS/LSIL Triage Study, and Alternatives in Women’s Health Care) trial reported that, for the patients tracked in this study, Digene’s HPV test demonstrated better sensitivity and specificity than the Pap smear. ALTS is a $20 million, five-year trial involving about 7,200 women with mild Pap smear abnormalities.
Digene’s Technology Approved in Europe
Recently both France and Switzerland approved Digene Corporation’s Hybrid Capture® II HBV test for marketing in their countries.
Digene uses the same DNA technology in this hepatitis test as it does in its human papillomavirus test. The company has high hopes that Europe will develop into a lucrative market for its test products.
Within the United States, Digene announced that the Food and Drug Administration (FDA) granted marketing clearance to Digene’s Hybrid Capture II Chlamydia/Gonorrhea test. It is used to test women, with or without symptoms, to identify or confirm the presence of both chlamydia and gonorrhea. The test can simultaneously identify both organisms.
Abbott Laboratories, Inc. distributes these tests for Digene in Europe, Africa and the Middle East. Abbott will also handle distribution of these tests in the United States.
Merit In Further Evaluation
Obviously, these developments are too recent for the pathology community to develop any consensus about their meaning. But from a strategic market perspective, they are signs that a growing volume of clinical studies indicate there is merit in further evaluating the relationship between HPV and cervical cancer.
That evaluation is about to commence in Great Britain. Late in February, it was disclosed that the United Kingdom would launch a pilot study involving Digene’s HPV test. The one-year test, starting this summer, will test women for HPV if they have a mild or borderline Pap smear result. Women testing positive for HPV will be referred immediately for further treatment.
Women testing negative for HPV will, at six months, be offered a second HPV test with their Pap smear. If they test HPV-negative at this time, and if their cervical abnormality has not progressed to high-grade disease, they will return to a normal screening cycle.
Obviously, the UK’s National Health Service believes enough credible clinical trial data about Digene’s HPV test exists to justify moving forward with this pilot study.
Other combatants in the Pap smear war are Cytyc and TriPath Imaging. Recently, each company has its own victory to report. For Cytyc, it was the announcement that the Family Planning Association of Hong Kong would begin using Cytyc’s ThinPrep® System for all its Pap smear testing. This involves about 100,000 Pap smears per year.
The interesting question is whether further clinical trials and studies will demonstrate that HPV indisputably causes cervical cancer. If that were to occur, DNA-based blood tests for HPV could supplant Pap smears as the clinical gold standard.
At TriPath Imaging, a total of six clinical trials were reported during the recent International Academy of Cytology (IAC) conference in Chicago, Illinois. Three trials reported favorable results from the use of TriPath’s Prep® automated thin layer preparation system.
Of particular interest, one of the AutoPap studies involved the routine screening of 100,000 Pap smears at Unilab Corporation in Tarzana, California. This study involved large numbers of patients and provides comprehensive data on how automated primary screening actually works in high- volume commercial laboratories.
THE DARK REPORT expects the pace of innovation in Pap smear testing will speed up during the next 24 months. This is because five years of efforts by Cytyc and TriPath have laid a foundation for accelerated change.
First, CPT codes are now established for most of the new Pap smear technologies. Both Medicare and private payers are becoming familiar with new Pap smear technology and making decisions on how to reimburse for such procedures.
Second, the sales forces of Cytyc and TriPath Imaging have been hammering at prospective laboratory buyers for five years. It’s been a slow process to educate pathologists and cytotechs about these new technologies. But there is now greater understanding about these technologies than there was five years ago. This will support faster decision making by pathologists and lab executives during the next two years.
Third, Digene’s DNA-based blood test for HPV represents a potentially new method to screen for cervical cancer. Like the enhanced Pap smear technologies, it is reasonable to expect that Digene will continue to improve its HPV assay. This fact, combined with more detailed data from an ever-increasing use of this test in clinical studies, will change the way Digene’s HPV test currently performs against the traditional Pap smear.
Adopt New Products
THE DARK REPORT predicts that the Pap smear marketplace is about to undergo an unpredictable transformation. Growing evidence that at least some of the enhanced Pap technologies generate better results than a traditional Pap smear will cause some clinicians and payers to adopt these new products.
The interesting question is whether further clinical trials and studies will demonstrate that HPV indisputably causes cervical cancer. If that were to occur, DNA-based blood tests for HPV could eventually supplant Pap smears as the clinical gold standard.