‘Quality monitors, test validation made ever more critical’ in cervical cancer screening
February 2015—Two medical organizations said that using an HPV test alone for cervical cancer screening is an effective alternative to the current recommendation for screening with either cytology alone or cotesting with cytology and HPV testing. Pathology leaders said the multispecialty-developed guidance leaves the Pap test standing as a first-line screening option.
The Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology issued the interim guidance report following the FDA’s April 2014 approval of Roche’s Cobas HPV test as a primary standalone screen for cervical cancer in women 25 and older. The guidance report was published jointly by Gynecologic Oncology, Journal of Lower Genital Tract Disease, and Obstetrics and Gynecology (Huh WK, et al. Obstet Gynecol. 2015;125[2]:330–337).
“Our review of the data indicates that primary HPV testing misses less precancer and cancer than cytology alone. The guidance panel felt that primary HPV screening can be considered as an option for women being screened for cervical cancer,” Warner K. Huh, MD, said in a statement. He is lead author of the interim guidance report and division director and professor in the Division of Gynecologic Oncology at the University of Alabama.
The report recommends considering primary HPV testing for women starting at age 25. Younger women should continue to get tested starting with cytology alone at 21. Women with a negative primary HPV test result should not be retested again for three years. This is the same screening interval recommended under current guidelines for a normal cytology test result.
The interim guidance panel consisted of 13 experts, including representatives from the SGO, ASCCP, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, the CAP, and the American Society for Clinical Pathology. Leaders within pathology lauded the collaborative approach the interim guidance panel took in developing its recommendations.
“The cytopathology community has been well represented through the coordinated efforts of pathology professional organizations—the CAP, ASC, ASCP, the American Society for Cytotechnology—to convey the pathology perspective on primary HPV screening,” CAP Cytopathology Committee chair Barbara Crothers, DO, and ASC immediate past president Ritu Nayar, MD, said in a joint statement to CAP TODAY. “This was accomplished through the Cytopathology Education and Technology Consortium, in addition to the participation of our joint ASC/ASCP/CAP cytopathologist representatives, Diane Davey, MD, and Robert Goulart, MD, in the ASCCP/SGO task force that developed interim guidelines for managing women who are screened for cervical cancer and its precursor lesions by the primary HPV testing only option.”
“The pathology community remains concerned about access to cervical cancer screening, regardless of the method, and about ensuring safe quality practices that provide accurate screening and confirmatory tests, including cervical biopsies,” Drs. Crothers and Nayar added.
Drs. Davey, Goulart, Nayar, and Patricia Tiscornia-Wasserman, MD, recently published a review of primary HPV screening for cervical cancer that covered details of the FDA approval and pertinent clinical trials (Nayar R, et al. Cancer Cytopathol. 2014;122[10]:720–729).
Dr. Davey
Dr. Davey, also a member of the CAP’s Cytopathology Committee, tells CAP TODAY that many pathologists may be concerned that the approval of primary HPV testing will lead to the demise of the Pap test, “historically the most successful cancer screening test ever.
“However, the guidance document emphasizes that primary HPV screening will be one of three screening options,” says Dr. Davey, professor of pathology and interim chair of clinical sciences at the University of Central Florida. “Additional clinical studies in actual practice settings and long-term follow-up are critical to determine whether primary HPV screening offers any advantages over cotesting or cytology alone.”
Dr. Goulart, the other pathology representative on the ASCCP/SGO panel, adds that the pathologist, cytotechnologist, and laboratory medicine community must work closely with clinical colleagues to ensure primary HPV cervicovaginal screening is performed using HPV tests FDA-approved for that indication.
“Attention to quality monitors and test validation is made ever more critical by the loss of the morphologic control offered by microscopic review of the Pap slide,” says Dr. Goulart, president and director of cytopathology at New England Pathology Associates, Springfield, Mass.
Foundation CMO: Roche deal to spread genomic testing
Roche announced it will buy up 56 percent of the shares of Foundation Medicine as part of a broad strategic collaboration that will give Roche an opportunity to use FMI’s molecular information and genomic analysis to identify and develop new cancer treatments.
Dr. Miller
Foundation Medicine’s chief medical officer, Vincent Miller, MD, tells CAP TODAY the cash infusion from Roche also will speed his firm’s genomic testing advancements and help broaden awareness of the centrality of such diagnostics in cancer treatment.
“What we’re excited about in our partnership is the opportunity to accelerate and deepen the educational roots in some places that are not really laid down yet,” Dr. Miller says. “We believe that working with more oncologists, and working with more pathologists in looking at the information from our approach is going to be absolutely essential to raising the tide for all boats, so to speak.
“One of the things that the CAP, the AMP [Association for Molecular Pathology], and others have commented on is that even for markers where there’s no dispute of the need for genomic testing to be done for certain tumor types, the percentage of patients who have that marker tested is far from 95 percent,” he adds. “We need to reach into community practices with our surgical, pathology, and oncology partners to educate them about the necessity for genomic profiling in 2015 and going forward.”
Dr. Miller adds that joining with Roche will enhance Foundation Medicine’s ability to better its testing services.
“We have insights from our pharmaceutical partners as to what programs they might be bringing to the clinic in eight or 12 or 24 months down the line,” he says. “Because of that, our test content tends to be forward-looking. If we’re exactly on guideline, then almost by definition we’re going to be behind. By adding Roche’s insight—they have one of the world’s deepest pharma pipelines—we will certainly improve the content of our tests.”
Foundation Medicine will remain operationally independent and will continue to be run by president and CEO Michael J. Pellini, MD.
ACLA’s legal eagles slam FDA ‘overreach’ on LDTs
The American Clinical Laboratory Association released a white paper that aims to provide a systematic and detailed rejection of the FDA’s proposal to extend its regulatory authority over laboratory-developed tests by reclassifying them as medical devices.
The white paper, written by former Bush administration solicitor general Paul Clement and Harvard University constitutional law professor Laurence Tribe, was released a day ahead of the FDA’s two-day January public hearing on its proposal to phase in regulation of LDTs over the course of a decade.
“FDA’s novel effort to expand its jurisdiction is foreclosed by the plain text of the FDCA [Food, Drug, and Cosmetic Act],” Clement and Tribe wrote. “Congress gave FDA the authority to regulate medical devices, and laboratory-developed testing services are not devices.”
The 25-page ACLA white paper dubs the FDA’s LDT oversight proposal a “dramatic overreach,” and advises the agency to withdraw its draft guidance. The document is available at http://j.mp/aclaldts.
Meanwhile, the two-day FDA hearing featured a wide array of testimony from stakeholders. Several speakers representing the CAP urged the FDA to make significant changes to its plan. Among the objections is that the agency’s proposal would classify too many tests into a high-risk category.
“Based on the draft guidance as written, we estimate 1,000 LDTs considered to be companion diagnostics will be classified as high-risk LDTs and require [premarket approvals] despite these tests being well-established in medical practice and the standard of care,” said Gail Vance, MD, a member of the CAP’s Personalized Health Care Committee.
The CAP also recommended that an LDT used within a health care network be treated as a “traditional LDT” exempt from premarket approval. In addition, minor changes to LDTs should not be treated as entirely new tests, said Emily Volk, MD, vice chair of the CAP’s Council on Government and Professional Affairs Committee.
“Some laboratories have modified a test to automate a manual method,” Dr. Volk said. “The clinical claim and performance characteristics for the test do not change.”
CAP president Gene N. Herbek, MD, expanded on these and other points in written comments submitted to the FDA on Feb. 2. The 58-page document is at http://j.mp/capldtletter.
“There are significant differences in how our proposal defines an LDT and the risk classification for LDTs,” Dr. Herbek wrote. “We also differ in our view of the appropriate role of CLIA and the CMS within the regulatory process.”
Report: Where mistakes are most likely to occur
An analysis of nearly 2,700 diagnosis-related malpractice cases in ambulatory care finds that foul-ups in testing and results processing were the least likely source of missed or delayed diagnoses.
Twenty-nine percent of the cases involved testing failures of some kind, “from the scheduling, performance, and interpretation of diagnostic tests, through the management of test results,” the report said. Fifty-eight percent of cases involved the initial diagnostic assessment, and 46 percent of cases were follow-up and coordination failures.
Within testing, “the factors that trigger malpractice allegations are primarily related to breakdowns in clinical systems for test result management, the cognitive skills related to interpretation, and communication of results to the ordering physicians,” said the report, released by CRICO Strategies, a division of the Risk Management Foundation of Harvard Medical Institutions.
Missteps in test performance included failing to perform ordered tests, incorrectly performing the tests, and mishandling or mislabeling the specimens. These contributed to just three percent of the diagnostic errors examined, and pathology was identified as the primary responsible service in just 16 percent of these cases, said Gretchen Ruoff, MPH, of CRICO, who provided some pathology-specific data not in the report. Another area within testing that contributed to five percent of diagnostic errors was the ordering physician not having received or reviewed the test result, or having done so after a significant delay. Pathology was pinpointed as the responsible service in only six percent of these results-communication mixups.
Mistakes in interpretation, involved in 23 percent of the testing-related cases analyzed, included incomplete or inaccurate reports and failure to rule out abnormal findings.
There were 608 cases involving a misinterpreted test, said the December report, “2014 Annual Benchmarking Report: Malpractice Risks in the Diagnostic Process.” The service responsible for the final diagnosis in these cases was most frequently radiology, accounting for 49 percent of the misinterpretations. By comparison, 17 percent of misinterpretations involved pathology, in areas such as benign neoplasms, uterine or cervical cancer, and skin cancer. So, of the 2,685 ambulatory-based diagnosis-related malpractice cases analyzed, fewer than four percent involved misinterpretations by a pathologist.
—Kevin B. O’Reilly