Q: Have there been any concerns about previous Bethesda Systems?

Dr. Solomon: The original Bethesda System introduced a term known as "Atypical Squamous Cells of Undetermined Significance," which is a very long way of saying that the laboratory is not quite sure what the findings represent. This term has been shortened to an acronym known as ASCUS, which clinicians as well as laboratories have found very frustrating because it's not quite clear how to manage women who have this ambiguous ASCUS result.

And in fact the National Cancer Institute sponsored a clinical trial of women who have ASCUS, as well as low-grade squamous findings, to ask the question "What is the best way to manage women with these types of test results?" We've certainly learned a lot based on ALTS [ASCUS/LSIL Triage Study], which in fact has now informed the development of guidelines for managing women with these findings. So this is a case where the Bethesda terminology really prompted a clinical trial that has provided data that in turn was used in the development of clinical management guidelines.

It's a frustrating fact for laboratorians, clinicians, doctors, and women that there are limitations to any medical test. No screening test is perfect, and one of the limitations in terms of the Pap test, or cervical cytology, is that the findings are not always crystal clear. There are cell changes that are ambiguous and we have to recognize that. We have to try to reduce that ambiguous category to the lowest possible number, but we also have to acknowledge that that's one of the limitations of the test. I think the ALTS findings help us deal with that reality of the limitation of cervical screening.