Persistent infection with high-risk human papilloma virus (HPV) is a significant risk factor for developing cervical cancer and its precursor, cervical intraepithelial neoplastic lesions. The screening diagnosis is based on the cyto-morphologic effects of the virus on cervical epithelial cells; and early detection of a pre-malignant cervical lesion promises to improve the survival of the individual suffering from these condition. This approach was always the case, until molecular pathology allowed for testing for the virus itself.
Molecular pathology has brought about changes in the cytology lab ranging from protocols involving collection, screening and reporting; to changes regarding insurance and regulatory policies.
Rise of HPV Testing
The HPV DNA testing is a successful and effective strategy in redesigning cervical cancer screening programs. As we all have witnessed in the past few years, image-guided screening has become well accepted and the same sample collection allows for HPV reflex testing.
Molecular pathology's impact on the cytology lab was highlighted when the same samples for the Thin Prep (Hologic) slides were determined to be suitable for an in-vitro nucleic acid hybridization assay, marketed as the Digene HPV test (Digene has now merged with QIAGEN).
This assay was first introduced in 1999; it detects 13 high-risk HPV types and is considered the gold standard of HPV testing.1 Using one collection for a Pap screen and HPV testing is convenient, but the possibilities do not end there. This same suspension has allowed for the utilization of other test platforms directed to female cervical health.
Presently, the Thin Prep and SurePath (BD Diagnostics) specimen collection systems allow testing for HPV, Neisseria gonorrhea, Chlamydia trachomatis, Herpes simplex 1 and 2, cystic fibrosis and a prognostic indicator for cervical cancer.2
As an added credit to molecular pathology and HPV testing in particular, several alternative approaches to cervical cancer screening have been implemented. Strategies include HPV testing to identify women at high risk for cervical cancer. This paves the way for identifying cervical lesions without relying on cytology, with the opportunity to test for HPV without necessarily ordering a Pap screen.
Other practices involve reducing the screening frequency among women who have had at least one normal smear; and recommending regular follow-up, rather than treatment for young women with mildly abnormal smears. Also, modified screening (including image-guided approaches) has helped identify subsets of Pap smears that should be examined by cytologists. Treatment strategies, an increased emphasis on improving test accuracy and planning for client follow-up are instrumental to the continued success of these initiatives.
Another change brought about by molecular pathology involves the effective utilization of decision-support rules and the laboratory information system enabling them. Based on the ordering physician's request, these decision-support rules trigger reflex HPV testing when an atypical squamous cells of undetermined significance diagnosis or higher is made.
Laboratory information systems have been reconfigured to accommodate added correlations, historical results reviews and molecular tests based on Pap interpretation.
Pap reports themselves have also evolved. Molecular results are included in the Pap report together with the chronological history of the patient's cervical health. The combination of cytology and molecular results in one report means much of the Pap report is starting to resemble a quantitative panel.
The changes molecular pathology has to offer depend on the nature of the cytology laboratory (e.g., whether it is hospital or research based, or an independent reference laboratory). The technology is adaptable, so it is a matter of if the possibilities stir enough attention and interest. The laboratory's viability and profit margins are the usual motivators, but equally important are the issues of local competition, insurance reimbursement rates, and concerns regarding clinical and cost effectiveness.
The molecular diagnostics market is the fastest-growing segment of the in vitro diagnostics industry. The changes it has brought to the diagnostic laboratory are both significant and demanding. Molecular diagnostics provide investigative opportunities, at the same time dictating laboratory professionals' training needs. The cytology lab is no exception. DNA testing has the potential to open new exploratory opportunities and thus is a compelling force in both medical and business decisions.
The molecular diagnostics market is so profitable, pharmaceutical companies are increasingly becoming interested in developing tests that can be used with various methodologies. These companies represent the new and influential players in a field typically dominated by a few large diagnostics companies.
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