Growth Opportunities in Anatomic Pathology

Given the current industry trend of consolidation, where a few national laboratories increasingly dominate the market, and where reimbursements are under pressure, opportunities to increase capacity, enhance revenue, and mitigate liability are scarce.

While many new technologies are often put forward as solutions, laboratories tend to review and evaluate only those technologies that may actually help them increase revenues, lower costs, broaden test offerings, improve quality standards, reduce risk, and, as an added bonus, increase workflow efficiencies.

For laboratories providing cytology services, improving any or all of these competencies can often lead to real growth.
A viable solution for a growing number of cytology laboratories is the adoption of automation using the ThinPrep® System, which includes the ThinPrep Pap Test and the ThinPrep Imaging System with Dual Review. The ThinPrep Pap Test provides a standardized approach for Pap testing and molecular testing out of one patient vial, and the ThinPrep Imaging System synergizes the strengths of both human and computerized slide review, creating opportunity for growth, differentiation, and standardization.

Consolidating Marketplace: For laboratories, the marketplace has been consolidating in favor of a few, large national laboratories. Managed care has driven consolidation through competitive bidding, which results in potentially lower revenues. For example, a laboratory with regional operations has recently lost a customer with 40,000 Pap tests annually to a large, national lab because the primary HMO decided to switch providers to cut costs. As profits decrease, opportunities for growth and differentiation are reduced, making it difficult to stay competitive.

Workflow Inefficiencies: The challenge of staying competitive in an environment of decreasing revenues makes lean operations and standardization crucial, yet challenging, components of decision making. For example, shortage of cytotechnologists in one lab results in a backlog and five-day turnaround time. A competing lab offers a two-day turnaround time and is therefore able to market this improved efficiency and gain new business. Increased throughput capacity is needed, but staffing issues make the process daunting. New technologies are needed that address staffing shortages in the lab, and thereby improve workflow inefficiencies. Additionally, as laboratories look to offer a broader test menu, an additional challenge is the coordination of molecular testing out of the Pap test vial.

Risk of Liability: Risk mitigation is achieved by meeting the standard of care. Bierig reports the standard of care is determined by expert testimony in malpractice suits based on several factors that include customary practice in similar situations, medical textbooks, peer-review literature, practice guidelines issued by professional societies, and any other reliable and relevant sources of information.1 Advances in healthcare technology that raise the standard of care are important to track and evaluate in terms of risk mitigation.

The American Society of Cytopathology last published practice standards in 2000. Laboratories may have an increased liability risk if the highest standard of care is not offered. In the October 23, 2006, edition of Advance News Magazine for Medical Laboratory Professionals, Karen Allen explained that errors subject to Pap test litigation fall into two general categories: process errors and interpretation errors.2 For example, false-negative cases are litigated much more often than false-positive cases. One of the most common sources of false negatives in Pap test screening is hyperchromatic, crowded groups of abnormal cells. Seeing into these clumps can be difficult, and abnormalities are easy to miss. However, liquid-based cytology removes blood, protein, and cellular debris, which obscure smears, thereby reducing the false-negative fraction.

Off-label use of diagnostic test kits is another source of liability.3 For example, the labeling for the HPV DNA test by the FDA advises that the test is “to augment existing diagnostic methods for the detection of cervical disease” and warns that the test “should not be used as the sole basis for clinical assessment and treatment of patients.”4 Despite this labeling, some practitioners have used the kit contrary to instructions as a primary management tool without cytology in women with prior cytologic or histological abnormalities. However grounded and well intentioned, this approach could expose the practitioner to risk of liability.

A solution is needed that addresses the challenges faced by laboratories providing gynecologic cytology caused by a consolidating marketplace, workflow inefficiencies, and risk of liability.

Gynecologic Cytology in Context

The development of the Pap smear in the 1940s by Dr. George Papanicolaou ushered in the modern era of cervical cancer screening. The main drawback of the conventional smear is that abnormal cells are easily missed by the reviewer because of poor slide quality, resulting in a “false-negative” diagnosis.

Increasing numbers of smears and a shortage of trained cytotechnologists drove efforts, beginning in the 1980s, to automate slide review and reduce or eliminate human interpretation. By the 1990s, two systems were available, but neither automated system was a match for the skills of a trained cytologist, and neither effectively addressed the high false-negative fraction. Poor slide quality and errors from Pap smears continued to be a problem.

The process of change began in 1988 when the Wall Street Journal published an article that highlighted the problem of false-negative Pap smears resulting from laboratory errors. The article reported that “cut-rate ‘Pap mills’ process slides using screeners with an incentive to rush.” The article led to public outcry over one or more deaths attributed to false-negative Pap smears and resulted in the federal Clinical Laboratory Improvement Act of 1988 (CLIA 88). This act mandated quality control and screening standards. Companies, such as Cytyc Corporation, began in earnest to address the problem of false negatives.

Fifty years after the Pap smear was invented, the first real improvement to cervical screening came in 1996 with the FDA approval of the first liquid-based cytology test: The ThinPrep® Pap Test produces a higher-quality slide that is easier for trained professionals to review without the blood, mucus, and inflammatory cells that obscure conventional “smears.” The result is improved disease detection with fewer false negatives. 5 The ThinPrep® Imaging System was introduced in 2003 and builds on the progress of the ThinPrep Pap Test by synergizing the strengths of both human and computerized slide review.

Dual Review: Combining the Strengths of Human and Computerized Reviews

A new class of imaging technology, called “dual review,” has emerged that addresses the critical shortcomings of cervical cytology screening. Dual review technology is defined by synergistic review that leverages the strengths of both computerized and human review. The dual review technology came to market in 2003 in the ThinPrep® Imaging System to assist in primary cervical cancer screening for cancerous and precancerous cells. The ThinPrep® Imaging System with Dual Review™ is the only FDA-approved product in this class and represents the first real improvement over manual slide review. With Dual Review every patient slide is analyzed by the Imager and screened by a cytotechnologist.

Specimens are collected in a ThinPrep® Pap Test vial in the clinicians office and then sent to the laboratory for processing on a ThinPrep processor. Slides are stained and then imaged with the ThinPrep Imaging System. The Imager scans every cell and cell cluster on the patients slide, measuring DNA content. The largest and darkest nuclei are identified so cells can be more accurately assessed for abnormalities by cytotechnologists. Cells of interest are highlighted for the cytotechnologists’ review, helping cytotehcnologist to better focus interpretive skills where it counts.

Using the ThinPrep Imaging System with Dual Review, accuracy compared to manual review is increased with a concomitant decrease in false negatives.6 This type of focused and synergistic dual review has been shown to improve cytotechnologist job satisfaction by reducing eye strain and fatigue while increasing efficiency and capacity.

In a recent study, 7 Dr. Richard Lozano, MD, Director of Cytology at the Pathology and Cytology Laboratory in Lexington, Kentucky, compared the ThinPrep Imaging System with manually screened slides. The results showed that an imaging system with dual review technology successfully combines the best of modern computing power with the unique interpretive skills possessed by trained cytotechnologists and pathologists to increase disease detection. The results of his study demonstrated a statistically significant increase in HSIL detection. Dr. Lozano said, “We believe this technology will make a significant contribution to cervical cancer screening and patient management.”

Evaluating New Technology

Investing in new technology is an important part of staying competitive with potentially positive impacts on growth, risk, and patient outcomes. When evaluating new laboratory technology, there are several important issues to consider.

Evolving Standards of Care: Is the standard of care advancing in a particular field? Does the peer-reviewed literature and FDA support the advance? Do patients and consumers expect the highest standard, and if so, what is the liability risk of not upgrading?

Patient Outcomes: What effect will the new technology have on patient outcomes? Will outcomes improve, stay the same, or worsen?

Workflow Efficiencies: What impact will the new technology have on workflow efficiencies? Will it increase capacity? What effects will it have on human resources in terms of recruitment, retention, and retraining? Will it improve operations? Can the technology be incorporated into a lean operation?

Differentiation: Does the technology allow you to stand out from other laboratories in the area? Is it a marketing differentiator?

Choosing a Technology Partner: Does the technology company have a proven implementation team that will analyze specific business needs and customize the solution to meet them?

Support Resources: Does the technology company provide support resources for marketing, training, and educational opportunities?

The technological advance behind the ThinPrep Imaging System with Dual Review in many labs has shown improved patient outcomes and a positive impact on the business of cytology (Please refer to Table 1 below).

Dual Review in the Real World

An effective dual review solution leverages the strengths of human review with those of computerized review to improve patient outcomes.

Standard of Care: The standard of care in anatomic pathology is moving in the direction of a dual review system. Over 70% of Pap screening in the United States is performed with the ThinPrep Pap Test.8 Of these, over 45% are imaged with the ThinPrep Imaging System with Dual Review.9

Improved Patient Outcomes: Study results published by Dziura and colleagues show overall improved detection of cervical SIL compared to manual screening.10 Lozano found significantly increased detection of cervical abnormalities with dual review imaging compared with manual review alone. 11 Miller found increases in disease detection along with a fifty percent reduction in the false negative fraction.12

By combining the ThinPrep Pap Test with the ThinPrep Imaging System, laboratories are demonstrating improved clinical outcomes.

Section 5: Conclusion

New technologies will continue to change the face of anatomic pathology.

Labs today face many challenges, and revenue generation and competitive differentiation are key to their success. Cytyc’s ThinPrep® Imaging System with Dual ReviewTM overcomes many of the inherent challenges of a consolidating marketplace, workflow ineffciencies, and liability. By synergistically combining the strengths of human and computerized slide review, Cytyc is advancing the standard of care in anatomic pathology and thereby creating a positive impact on both patient and business outcomes

1. Bierig JR. Liability and payment issues in the selection of pathology assays. Arch Pathol Lab Med. 2002;126:652-657.
2. Allen KA. Avoid litigation by knowing how to consistently asses test evaluation. Advance News Magazines for Medical Laboratory Professionals 18[22], 10-12. October 23, 2006. King of Prussia, PA, Merion Publishers.
3. Bierig JR, Axelrad S. Malpractice issues to keep in mind in using diagnotic kits contrary to product labeling. CapToday, November 29, 2006.
4. Digene Corporation. hc2 Hybrid Capture 2 High-Risk HPV DNA Test: An in Vitro Nucleic Acid Hybridization Assay with Signal Plate Amplification Using Microplate Chemiluminescence for the Qualitative Detection of Human Papilloma Virus (HPV) Types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68 in Cerivcal Specimens. 2004. Gaithersburg, MD, Digene Corporation.
5. Versus the conventional Pap smear, Cytyc Corporation. The ThinPrep Pap Test package insert results based on a multisite, prospective, historically controlled, direct-to-vial study of routine screening and referral patient populations at 10 leading academic institutions resulting in a 59.7% increase of HSIL+ lesions for ThinPrep specimens. Refernece” ThinPrep Pap Test Package Insert Part no. 04141-002 Rev C.00.
6. Greater accuracy is based on a statistically significant improvement in sensitivity for ASC-US+ and a statistically significant improvement in specificity for HSIL+ from the ThinPrep Imaging System clinical trial. False negative reduction is based on a statistically significant improvement in sensitivity for ASC-US+ from the ThinPrep Imaging System clinical trail. Reference: ThinPrep Imaging System Operation Summary and Clinical Information.
7. Lozano R. Comparison of computer-assisted and manual screening of cervical cytology. Gynecol Oncol. 2006; 104:134-138.
8. Cytyc Corporation 2007. Data on file
9. Cytyc Corporation 2007. Data on file.
10. Dziura B, Quinn S, Richard K. Performance of an imaging system vs. manual screening in the detection of squamous intraepithelial lesions of the uterine cervix. Acta Cytol. 2006;50:309-311.
11. Lozano R. Comparison of computer-assisted and manual screening of cervical cytology. Gynecol Oncol. 2006;104:134-138.
12. Miller et al., Implementation of the ThinPrep Imaging System in a High-Volume Metropolitan Laboratory Diag Cytopath 2007; 35:213-217.