IVD Technology Magazine | IVDT Article Index
Originally published May 1996
IVD Technology - NEWS
Will the HPV DNA test upstage the Pap smear?
It's little wonder that the automated Pap smear has found rapid acceptance in the clinical laboratory. The traditional Pap smear is notorious for its high false-negative rate. But now an FDA-approved assay for a cervical cancer marker has arrived, allowing much more accurate diagnosis. The assay detects infection by certain types of human papillomavirus (HPV) that are associated with increased risk of cervical cancer.
Digene, Inc. (Silver Spring, MD), developed the DNA-based diagnostic employing its Hybrid Capture method. In direct comparisons with Pap smears, the HPV DNA test has significantly greater sensitivity for premalignant lesions--what physicians refer to as grades II or III of cervical intraepithelial neoplasia, says Attila Lorincz, PhD, vice president and scientific director of Digene.
Indications for the HPV DNA test are expected to be included in new guidelines issued this year by the American Society for Colposcopy and Cervical Pathology (Washington, DC). The document, "Management Guidelines for Atypical Squamous Cells of Undetermined Significance," is expected to be published this spring.
In April, a scientific panel convened by the National Institutes of Health (NIH) concluded that HPV is a principal cause of cervical cancer. Some HPV types integrate with human DNA, a feature believed to account for the invasiveness of certain forms. The panelists stressed the importance of educating health-care providers about the causal link. Historically, this kind of pronouncement--official recognition of a cause-and- effect relationship--has preceded a call for changes in testing.
The traditional Pap smear is entrenched in the American health system, though, and a change will take years. The American College of Obstetricians and Gynecologists (ACOG), for example, does not endorse HPV DNA testing. When it examined the concept two years ago, the organization concluded that the "clinical expression of HPV is highly variable," and that the lesions are subject to "spontaneous regression and recurrence."
Lorincz agrees that certain HPV infections are transient and will disappear on their own. Digene's third-generation test, however, uses new, multiple DNA probes to detect only those types of HPV that cause the persistent infections most closely associated with increased risk for cervical cancer.
A year ago, ACOG's Committee on Gynecologic Practice designated women with current or prior HPV infection as being at high risk for cervical cancer. This, together with the recent findings by the NIH panel, may make the committee take a new look at the issue, said Alice Kirkman, public information specialist for ACOG. And if ACOG revises its recommendations, the Society of Gynecologic Oncologists (Chicago) is likely to follow suit.
HPV DNA detection has won widespread support among pathologists, if not OB/GYNs. HPV DNA testing is the wave of the future in cervical cancer screening, according to Carl Treling, MD, chair of pathology at Queen of Angels/Hollywood Presbyterian Hospital in Los Angeles. "If you have some reliable way to screen for HPV, you won't even need the Pap smear," he says. "But it will take ACOG cheering it on" to ensure acceptance into medical practice, he adds.
"In the short term, this will not replace the Pap smear in the United States," Lorincz agrees. In developing countries, where the Pap smear is not so well established, "we think HPV DNA will become the de facto test for cervical cancer," he says.
Last year, the Canadian Task Force on the Periodic Health Examination, a panel that evaluates tests and procedures for that nation's health system, reviewed the evidence on HPV DNA screening and decided not to recommend including it in routine exams. The task force cited as one major limitation the fact that hybridization techniques are relatively new.
Another barrier to widespread acceptance of the HPV DNA test is the recent FDA clearance of two automated Pap smear analyzers for QC use. Clinical laboratories that have invested in these systems, which are designed to reduce the false-negative rate of Pap smears, will be loath to find them less universally applicable.
The AutoPap 300QC, from Neopath, Inc. (Redmond, WA), is showing great promise. It reviews negative slides and selects the 10% with the most suspicious cells for cytotechnologists to rereview, to see if they contain a missed abnormality.
Lorincz hypothesizes that widespread use of the automated Pap smear analyzers could actually increase demand for the HPV DNA test. With the automated systems, the number of Pap smears judged to be equivocal would increase, swamping scarce personnel and resources. The HPV DNA test could be used for triage to determine which patients with equivocal Pap smear results are at highest risk and require immediate follow-up invasive diagnostic procedures.
How well the Hybrid Capture HPV test fares in today's competitive environment will probably depend on the way it is received by the medical community and managed-care providers. Good data are just not enough to ensure reimbursement, cautions Don White, spokesman for the American Association of Health Plans (Washington, DC). Reimbursement by HMOs often goes hand in hand with a medical consensus, says White. Support by an NIH consensus conference or multiple clinical trials specifically endorsing a testing protocol is what is compelling, he stresses.
--Anne Scheck
