In the United States, there are an estimated 12,200 cases of cervical cancer resulting in approximately 4,100 deaths each year. A recent FDA approval has given the go-ahead on a combination test that will assist physicians in determining which patients are low-risk or high-risk for developing cervical cancer. It is estimated that over 30 million women age 30 and older that are screened in the U.S. each year will benefit from this testing.
While routine Pap smears find cell changes that may lead to cervical cancer, the expanded combination test detects what is believed to be the real culprit – HPV, a virus that has been shown to be leading cause of cervical cancer. Called the DNAwithPap and designed by Digene Corporation, of Gaithersburg, Md., the test combines Digene’s Hybrid Capture 2 HPV DNA test for human papillomavirus with a Pap test. The development should help physicians determine which patients are at extremely low risk for cervical cancer and which patients may be monitored more closely. Studies show the testing combination provides a very high certainty that a woman with a normal Pap result who is HPV-negative is at low risk for having or developing high-grade cervical disease or cancer in the near long term.
The break point for the test is age 30 and over. Women at this age are less likely to have HPV infection, but more likely to harbor persistent infection with high-risk HPV, which studies show can lead to cervical cancer.
Digene presented data at an FDA Advisory Panel Meeting in March 2002 derived from already or subsequently published studies involving over 40,000 women around the world. The data indicated that testing with Digene’s hc2 HR HPV DNA Test and the Pap test together is more sensitive than a Pap test alone for the detection of cervical cancer and its precursors. The American Cancer Society (ACS) recently recommended, contingent upon FDA approval, that the combination test be considered as an alternative for routine screening based on studies using Digene’s hc2 HR HPV DNA test.
The hc2 HR HPV DNA test, which detects the 13 key cancer-associated HPV types, is already FDA-approved as a follow-up for women with inconclusive or abnormal (ASCUS) Pap test results, regardless of age, to help determine which women need additional follow-up testing.
Thermo and Quest launch an automated CF test
Thermo Electron Corporation of Waltham, Mass. and Quest Diagnostics Incorporated of Teterboro, N.J. have collaborated to make available an automated, biochip-based laboratory test for the detection of cystic fibrosis (CF) gene mutations during prenatal screening. The new biochip array can be used for multiplex testing, which allows multiple DNA targets to be detected simultaneously in a high-production commercial laboratory setting.
The new biochip, called the CF Portrait, is being used at Quest Diagnostics Nichols Institute in San Juan Capistrano, Calif., to perform cystic fibrosis carrier screening. The CF Portrait process is expected to be used for all such screening at Nichols Institute by July 1, 2003.
The CF Portrait biochip is designed and manufactured by Thermo’s BioStar unit, and uses its proprietary Optical ImmunoAssay (OIA) technology to fully automate the detection of nucleic acid hybridization. The biochip is used in conjunction with Quest Diagnostics’ DNA extraction and amplification methods.
FDA says labs should advise physicians on limitations of rapid flu tests and potential for underlying bacterial infection
According to an FDA Lab Tip, rapid influenza diagnostic tests performed on individuals with signs and symptoms consistent with influenza appear to be moderately to reasonably accurate dependent on when testing is performed during the influenza season. Potentially the rapid time for results can be very useful for managing patients with suspected influenza and for detection of institutional influenza outbreaks. However, the FDA advises, positive testing must not be used alone to determine the cause of an individual’s symptoms. Often an individual may be co-infected with another pathogen that is the underlying cause of the symptom. Use of rapid influenza virus testing and missing an underlying cause was the subject of a public health advisory from the Centers for Drugs Evaluation and Research. The advisory followed several deaths where individuals were treated with antiviral medication but died from an underlying bacterial infection.
The FDA advises laboratories to make sure that physicians using these rapid test results understand the limitations of the tests, use clinical experience, further laboratory testing, and consider local surveillance data about circulating influenza viruses when interpreting test results.
Seven rapid influenza tests have been FDA-cleared; these tests can produce results within 30 minutes. BD’s Directigen Flu A test can detect only antigens associated with influenza A virus. Binax’s NOW Flu A, Binax’s NOW Flu B, and BD’s Directigen Flu A+B can detect and distinguish between influenza A and B virus antigens. Quidel’s QuickVue Influenza and Thermo BioStar FLU OIA can detect but do not distinguish between influenza A and B antigens. ZymeTx’s ZstatFlu test can detect neuraminidase the presence of which denotes a high probability that infectious virions are present; it also does not distinguish between influenza A and B.
The Quidel Quick Vue and ZymeTx’s ZstatFlu and Quidel’s QuickVue influenza tests are considered low complexity and may be used in physicians’ offices. The other five tests mentioned above are considered moderately complex and are for use in a hospital or clinical reference laboratories.
Oral contraceptives increase C-Reactive Protein
A recent study titled, “Oral Contraceptive Use and Increased Plasma Concentration of C-reactive Protein,” suggests that estrogenic hormones significantly affect pro-flammatory pathways. These findings, combined with previous studies linking oral contraceptive (OC) use with risks for ischemic stroke and myocardial infarction, impaired blood anticoagulent pathways, and increased cardiovascular reactivity, offer a potential explanation of complications that women experience from taking birth control pills.
Exploring this relationship, researchers from Galileo Pharmaceuticals, Santa Clara, CA and the University of Minnesota, St. Paul, MN conducted their study based on the idea that certain levels of the C-reactive protein (CRP) in the body is an indicator of cardiovascular risk.
Using a high sensitivity CRP test, researchers measured CRP levels using stored samples from 30 premenopausal women, ranging in ages 18-40. The female participants had previously taken part in a randomized, crossover study of the effects of soy intake on sex hormone metabolism in OC users and non-users. Four fasting blood samples and 24-hour urine (two mid-follicular and two mid-luteal) were collected from each participant over two menstrual cycles and were stored at –700ºC until laboratory analysis. OC users provided fasting blood samples on days 8 and 22 after menses. Plasma samples were later thawed and assayed for CRP by use of a high-sensitivity assay.
Results from the study showed that plasma CRP levels were two times higher among OC users than among non-users independent of diet assignment, diet treatment order, and phase of the menstrual cycle, suggesting that estrogenic hormones significantly affect pro-inflammatory pathways.
Concluding that a relationship exists between low-dose oral contraceptives and levels of plasma CRP in women, researchers from the study also suggest that the impact of OC use on CRP and inflammatory parameters should be investigated in prospective trials.
The study was presented at the American Physiological Society’s conference, Experimental Biology 2003, held in April 2003.
Common thyroid cancer gene mutation found
Thyroid cancer affects 22,000 Americans each year and makes up about a half of all head and neck cancers. Papillary thyroid tumors account for about 75 percent of all thyroid cancer and occur mostly in women. Until recently, there have been no real major genetic discoveries for common thyroid cancers.
Researchers at the John Hopkins Kimmel Cancer Center have found that a single genetic mistake causes about two-thirds of papillary thyroid cancers. Their research, published in the April 16, 2003 issue of the Journal of the National Cancer Institute, identified a mutation of the BRAF gene in 68 percent of papillary thyroid cancers.
The mistake in this mutation involves a switch of T (thymine) to A (adenine). The researchers found that this single coding error among more than 2000 nucleotides in the gene causes it to be stuck in the “on” position making thyroid cells continuously grow and divide, ultimately into cancer.
With this discovery, researchers hope to find better diagnostics and drug therapies designed to target the effects of the mutation. David Sidransky, M.D., professor of otolaryngology and oncology at John Hopkins says, “though most thyroid cancers can be cured by surgery and radioactive iodine treatments, it remains difficult to distinguish benign thyriod disease from cancer.”
“Improvements in diagnostic tests and treatments using what we know about the BRAF mutation could speed up diagnosis and help patients survive advanced disease,” says Sidransky.
Hopkins researchers also screened for the BRAF mutation in other cancers and thyroid tumors. Six out of nine thyroid cancer cell lines tested positive for the BRAF mutation. No mutations were found in biopsies from 20 benign thyroid conditions and other types of thyroid cancer. A research team at the Wellcome Trust Sanger Institute recently found the same mutation in the BRAF gene in approximately 80 percent of melanomas and some colon cancers.
Bayer launches four fully automated HBV tests outside the US
Bayer Diagnostics’ Advia Centaur
The Diagnostics Division of Bayer HealthCare in Tarrytown, N.Y. announced the availability outside the US of four fully automated hepatitis B assays, Anti-HBs, HBc Total, HBcIgM, and HBsAg, on the Advia Centaur immunoassay system. These assays are run alone or in combination with one another to aid in the diagnosis of hepatitis B virus (HBV) infections. The assays are only available outside the United States.
In offering this complete panel of Hepatitis B assays on the Advia Centaur immunoassay system, Bayer is targeting medium and large volume laboratories. The addition of these assays enhances the level of testing automation with such features as: software that provides automatic algorithm processing, cascade reflex testing, user-defined panels, automatic repeats of critical samples, and sample and reagent integrity checks.
The Hepatitis B assays are currently available in European, Latin American and Asia Pacific countries outside of the United States. Bayer is applying for the United States Food Drug and Administration (FDA) approval. Sales will commence upon receipt of approvals.
Predicting drug resistance in hepatitis B patients
Findings presented by researchers from Georgetown University Medical Center at the April 2003 International Conference for Antiviral Research show that the presence of DNA markers can predict which hepatitis B infected patients will respond successfully to the drug lamivudine and which are likely to develop drug resistance or reject the drug altogether. Lamivudine is one of the most commonly prescribed treatments for HBV, but many doctors wait to prescribe the drug until clinical illness is manifested, because drug resistance will develop in two thirds of treated patients.
“We have long struggled with one tough question: how do you treat those HBV-positive people who have the best chance at responding to lamivudine treatment and determine those who will fail treatment?” said Dr. John Gerin, professor of microbiology and immunology at Georgetown University Medical Center. “Doctors currently play ‘wait and see’ — wait until you get sick and then we’ll see if lamivudine works. With a precise, predictive system in place, we can give patients immediate and targeted treatment rather than forcing them to wait until they become very ill.”
Two separate DNA polymorphisms were detected in the virus genome in all breakthroughs and non-responders prior to treatment, while none of the responders had these markers. “In an era of skyrocketing medical costs, the cost savings in not treating patients who will not respond may be a profound public health advantage,” said Gerin.
CDC initiative aims to boost HIV testing
The Centers for Disease Control and Prevention (CDC) has announced an initiative aimed at reducing the number of new HIV infections in the United States. The initiative includes making HIV testing a routine part of medical care, creating new models for diagnosing HIV infections outside medical settings, preventing new infections by working with people diagnosed with HIV and their partners, and further decreasing mother-to-child HIV transmission by incorporating HIV testing in the routine battery of prenatal tests.
Experts estimate that 850,000 to 950,000 persons are currently living with HIV in the United States and many of these individuals don’t know they are infected. In addition, an estimated 300 infants contract HIV from their mothers each year.
“It’s simply unacceptable that 40,000 people in this country become infected with HIV each year, and it’s intolerable that about one fourth of those infected with HIV don’t know they’re infected and therefore are not receiving appropriate medical care,” said Julie Gerberding, M.D., M.P.H., director of CDC. “This new initiative will go a long way to help frontline clinicians help people overcome some of the barriers they face getting diagnosed and treated for HIV.” The initiative capitalizes on new rapid testing technologies, specifically the OraQuick 20-minute HIV test that has recently been FDA approved and CLIA waived.
Officials have been concerned that the battle against HIV appears to have stalled, and rates of infection in certain high-risk populations have begun to rise. Many people are not tested until they are ill with the disease, but early identification of infection is imperative to maximize the effectiveness of antiretroviral therapy.
The first part of the initiative is to make voluntary HIV testing more routine. According to Gerberding, people living in an area where HIV is highly prevalent, or belonging to a risk group or having a behavior that increases their chance of exposure, should be asked in simple terms whether they have unsafe sex or use an injection drug. If their answer is affirmative or equivocal, they should be offered an HIV test. The requirement for extensive prevention counseling as a prerequisite to HIV testing is being removed from the CDC guidance. Gerberding said, “In the past, we have conditioned getting tested on acceptance and participation in a fairly comprehensive behavioral counseling intervention. That intervention is still critically important. We have evidence from research studies that it does help people change their behavior and reduce their risk. But in the medical environment, it’s a barrier to getting the test done because many clinicians either don’t know how to do that kind of counseling or simply don’t have the time to squeeze it into a very brief office encounter.” Though the requirement as a condition for testing will be removed, part of the CDC’s initiative is to assure access to prevention counseling as appropriate.
The initiative also targets access to rapid testing in community settings where people already have established trusting relationships. Routine testing had previously been recommended only for those visiting acute care hospitals with a high incidence of HIV cases and for those visiting STD clinics. The new measures could make routine testing far more widespread in physician offices, clinics, drug treatment centers, shelters, prisons and other nonmedical sites.
About $40 million is earmarked toward these projects. Details are published in the April 18, 2003 Mortality and Morbidity Weekly Report.
Dade introduces test interpretation software in Europe
Dade Behring of Deerfield, Ill., has announced the availability in Europe of the Protis software program, designed to support the interpretation and consolidation of multiple test results. The Protis software program consolidates all test results for a single patient into one assessment report and offers: interpretation of clinical results for CSF testing, urine analysis and specific protein profiles; test interpretation in editable text format providing users with suggestions for the interpretation of test results and allowing the addition of comments, observations and additional notes to the patient record; and presentation of test results in graph format. Protis also makes available on-line connectivity to Dade’s BN ProSpec and BN II, Dimension RxL and Xpand and BEP 2000 and BEP III instruments.
All patient results, including graphs, are displayed at-a-glance, enabling physicians to easily review the data and interpret results.
