Dan Levangie, senior vice president of commercial operations (standing), and David Zahniser, vice president of scientific affairs, in front of the Cytyc ThinPrep Imaging System.
In the fall, Cytyc enters clinical trials with its ThinPrep Imaging System, a follow-up technology to its successful ThinPrep PapTest, which was approved by the Food and Drug Administration in May 1996 and hailed as “significantly more effective” than the conventional Pap smear, developed in the 1940s. But it was the imaging system — not the improved Pap test — that Cytyc had been after from the beginning.
“The company was founded in the late 1980s with the original focus on developing an imaging system to read Pap smears,” said Dan Levangie, senior vice president of commercial operations. Since its introduction, the conventional Pap smear has been credited with reducing cervical cancer deaths by more than 70 percent. However, the 50 year-old technology is associated with a 20 to 40 percent false negative rate. Cytyc’s challenge was to increase accuracy and productivity in cervical cancer screening.
The ThinPrep Pap Test uses a fluid transport medium to preserve cells and a special processor to reduce debris and uniformly distribute cells on a slide. With the old Pap test, the doctor swabbed the cervix and then wiped the swab directly onto a slide. A ThinPrep-prepared slide is free of the obscuring blood, mucus and non-diagnostic debris that sometimes made reading a traditional Pap slide difficult.
ThinPrep currently is used by more than 11,000 U.S. physicians, Levangie said. Some offer the test as a supplement to the traditional Pap test while others use it as an alternative. With 15,000 new cases of the disease discovered each year and 4,000 to 5,000 deaths from cervical cancer annually, the ThinPrep test should greatly enhance the odds of catching the disease early, Levangie said. About 150 health insurance carriers, representing 130 million patients, currently reimburse for the ThinPrep Pap Test.
“Today about 20 to 25 percent of Pap tests are done with the ThinPrep, and by the end of this year it will be in excess of 30 percent,” he said. “We think it will become the new standard.”
Once development of the ThinPrep test was completed, a team of about 80 scientists and engineers from Cytyc and its engineering consultant, Battelle’s Medical Products Group of Columbus, Ohio, turned their attention to perfecting the imaging system. Developing the imaging system to read ThinPrep results couldn’t have come at a better time, Levangie said, as the number of cytotechnologists in the United States are on the wane.
“The fact is, a cytotechnologist’s life in the lab is mundane and tedious,” Levangie said. “They sit at a scope all day and look at slides, most of which are normal. It’s a very difficult position, and not many want to do it anymore.”
That makes an imaging system all the more attractive to labs, “It reduces their need for cytotech labor to read slides and will help relieve the problems associated with the shortage of them.”
The ThinPrep Imaging System pre-screens ThinPrep slides and flags potential abnormalities before they are seen by a cytotech. This can result in a time savings of 50 percent on negative slides, while increasing vigilance on abnormal slides.
|Research begins||First prototype||In-house studies on imaging systems||Clinical trials begin|
|1995||Nov. 1999||April 2000||Fall 2000|
During the development process on the ThinPrep Imaging System, several important correlations were noted, according to David Zahniser, vice president of scientific affairs at Cytyc.
“If you control the stain well, simple measurements performed on the nuclei of cells can catch abnormals,” he said. “Secondly, most normal preps have some cells which are abnormal looking to the imager and require human input to determine if they are abnormal or normal.
“This meant we needed an interactive system where the imager can find the rare event,” he said, adding that a human hand is still needed in the loop to make decisions that require judgment.
The system that evolved holds 250 slides and analyzes them automatically, each within three minutes, Zahniser said.
“Each slide is numbered, and that number gets read by the imager. Then the slide is analyzed, and the coordinates of the field containing objects of interest are stored. The next day or the next shift, the slide is put on an automatic scope. It reads the number, instructs the imaging system to download coordinates of interest and the microscope stage moves automatically to those areas of interest,” he said. “The cytotech looks at the field for abnormalities and signs of infection.”
The automated system moves through 15 to 30 pre-selected fields in much less time than it would take a cytotech to screen all 130 or so fields in a ThinPrep. At the end, the cytotech electronically indicates which objects may be of interest. If the majority of pre-selected fields are negative, the process goes quickly, increasing productivity. If something is flagged by the cytotechnologist as an area of concern, the slide is examined in its entirety and marked for a pathologist’s trained eye to examine.
Besides more efficient slide reading, augmenting the accuracy of cervical cancer diagnosis is the real benefit from using the computerized imaging system, Zahniser said. “We already have seen significant improvements using the ThinPrep Pap Test by itself,” he said. “We don’t know what the incremental increase in sensitivity will be (with the imaging system). It will be at least as accurate, we believe, if not slightly more.”
“When you think about what a cytology technologist does — looks through a microscope at normal cells all day — it’s a wonder that there aren’t more vigilance problems. And there are already plenty of well-documented problems with vigilance because the mind wanders,” he said. “With an imaging system directed to a limited number of potentially problematic fields, one could assume an increased level of vigilance in those fields of view.”