Putting HPV testing into everyday practice
Rick Lozano, MD
To bring human papillomavirus testing into your laboratory, start with education. Educate yourself, other pathologists, and your clinicians because all of you will face questions about laboratory policy and the clinical significance of HPV results. Your clinicians will ask about costs, turnaround time, and the laboratory ASC-US rate. Gauge the awareness level of your clinicians. Do they know about and are they following the guidelines of the American Society for Colposcopy and Cervical Pathology? Know your own laboratory data, specifically the ASC-US rate and ASC-US/SIL ratio. If your computer system can produce individualized statistics for each clinician, your lab could produce a much more personalized statistical report.
Research the market
Discuss HPV testing with each of your clinician groups, but choosing a few leaders among them may be helpful in testing the waters. Most important to discuss are the specific indications for HPV testing according to the ASCCP guidelines as well as other emerging indications, whether the HPV test will be ordered case by case or as an automatic reflex test, and what the expected turnaround time is.
Based on your laboratory costs and estimated laboratory reimbursement, you can decide whether it is cost-effective to do this test in house or send it to a reference laboratory. Your ASC-US rate may also play a part in your decision. For turnaround time purposes, you will probably need to run HPV testing at least once a week. A minimum number of tests is required for each run to be cost-effective.
The CPT code for HPV testing has existed for years, and therefore it will not have to go through the gap-fill process that liquid cytology faced. Reimbursement already exists for CPT code 88621 (Medi-care, $48.50). Know your outpatient payer-mix (for example, percentage Medicare, percentage Blue Cross); once you know that, you can determine your average reimbursement.
Know the ASC-US culture
Certain pressures may act to increase the ASC-US rate. Theoretically, if you interpreted every case as ASC-US, your false-negative rate would be zero. Psychologically, none of us wants to be wrong, and ASC-US interpretation offers a perfect middle ground where one is never entirely wrong. Years of increased laboratory scrutiny have instilled a culture of extreme caution within many laboratories. Many pathologists are reluctant to downgrade their cytotechnologist's preliminary ASC-US interpretation, reinforcing the use of this interpretation. HPV testing offers an objective method to monitor and assess laboratory ASC-US reporting practices.
Clarify the test request options
The clinician must order the HPV test. He or she can ask for standing orders with automatic HPV testing on all ASC-US cases. Alternatively, the test can be ordered as a reflex option on a case-by-case basis on the cytology requisition form. If HPV testing is not ordered as a reflex, ASC-US case results can be reported along with a clinician "alert" to the option of HPV testing. Verbal consent must be documented each time. Our laboratory faxes a requisition, which must be signed and faxed back to the laboratory.
You should update your laboratory directory of services to include these new test options. This is an opportunity to identify your preferred test method—that is, liquid-based Pap with reflex HPV testing. You can also include template standing order forms and single test order forms. If you have space on the requisition form, it may be helpful to include additional molecular tests such as chlamydia and gonococcus.
Your clinicians will need to know how critical adequate sampling is. While this has always been important, it is now more important than ever, because cytology and HPV testing, and other possible tests, will come from a single sample. Training the office staff is also critical. Who fills out the test requisition form? Oftentimes, secretarial staff, nurses, and nurse assistants complete crucial information on the form. They will need to know which test to order and the importance of completing insurance information and clinical history (routine screen versus followup/high risk). If the information is not correct, insurers may not cover the tests.
How to report the results
The Bethesda System 2001 recommends an integrated report when feasible rather than separate reports. The TBS 2001 alternatives are as follows:
- Issue an ASC-US interpretation, and then send the HPV results as an addendum. This may yield the fastest turnaround time. However, this option forces the clinician's office to manage multiple reports—possibly from multiple laboratories—before getting a final result.
- Issue a preliminary interpretation (or hold the interpretation) until the HPV results are available. You can then issue a combined report with the cytology and HPV results, including educational comments.
- Armed with the HPV results and your initial impression, you can re-review the cytology and make a final interpretation. This is the interpretive model. The HPV data give you immediate feedback, which can be used for self-education and improving case triage. An initial ASC-US interpretation may be downgraded or upgraded; the final report will include a revised interpretation with the HPV results. This method is labor-intensive but provides a polished product, which many of our clinicians prefer.
Follow your results
ASC-US cases generally yield a 40 to 50 percent HPV-positive rate, based on ALTS data. If your HPV-positive rate is significantly lower, your laboratory may be overinterpreting ASC-US. A higher rate may indicate the potential for underreporting ASC-US and missing some cases of SIL. Although CLIA requires cytohistologic correlation for SIL+ cases, correlating ASC-US cases provides many quality improvement benefits. Not all ASC-US/HPV-positive cytologies will have biopsy-proven abnormalities; however, be prepared to explain why your results differ significantly from expectations.
A few final points
It is easiest to do the HPV testing in or near the cytology laboratory. Therefore, store specimen bottles in close proximity to the lab and according to their accession day (or some other standardized method). The specimen vials expire after three weeks (FDA regulations). This places an emphasis on reporting results quickly, being able to identify and pull bottles quickly, and dumping expired vials properly.
If additional STD testing is ordered, mark the bottles and requisition forms to help identify such cases and keep them from falling through the cracks.
CLIA '88 allows cytotechnologists to perform high-complexity testing; however, whether this includes HPV testing is now being disputed. State regulations governing this issue may require the test to be performed by medical technologists or MLTs. Use of cytotechnologists in testing clearly affects cytotechnologist utilization, turnaround time, and cost.
Your laboratory procedure manual has to include HPV testing, as well as the method for triaging ASC-US cases, and reporting results.
If your laboratory performs HPV testing, your next CAP inspection will include a molecular laboratory checklist. And proficiency testing is available for HPV.
Dr. Lozano, of Cunningham Pathology Associates in Birmingham, Ala., is a member of the CAP Cytopathology Committee.