Researchers Urge Restraint in Ordering HPV Tests.
Nevertheless, physicians should seriously consider performing a repeat Pap smear instead of testing for human papillomavirus (HPV), Dr. Sara Hughes advised at the annual meeting of the Society of Gynecologic Oncologists.
"I'm concerned that before there is some agreement on how and when to use the HPV test, there will be a lot of unnecessary procedures done as a result of a positive HPV result simply because providers feel nervous about the positive result," Dr. Hughes, a resident in obstetrics and gynecology at Brigham and Women's Hospital in Boston, told this newspaper.
HPV testing for a Pap smear result of atypical squamous cells of undetermined significance (ASCUS) got a boost from the recently published ASCUS/LSIL Triage Study (ALTS). The study found that HPV testing was more sensitive in detecting underlying high-grade lesions than was a repeat Pap smear in women with a previous ASCUS result (96% vs. 85%) (J. Natl. Cancer Inst. 93:293-99, 2001).
Dr. Hughes said that a patient at her institution exemplifies the overmanagement that can result from a positive HPV test. Despite having normal colposcopy and biopsy results after testing positive for HPV, the patient was sent for a more in vasive investigation because both she and her physician were worried about the HPV result.
In a study presented by Dr. Hughes at the meeting, HPV testing identified virtually all high-grade lesions, but it also had a high false-positive rate. "Of all of the women who are positive for HPV, only 1 out of 10 of them will have a high-grade lesion. The rest of the women will be entirely normal," she said.
The retrospective study of 419 cases focused on 208 ASCUS samples, all of which had also been tested for high-risk HPV.
When the women returned for their second Pap smear, 64% had a normal result, 13% had a repeat ASCUS result, 13% had squamous intraepithelial lesions on Pap smear alone, 6% had squamous intraepithelial lesions on both Pap smear and biopsy, and 4% had high-grade squamous intraepithelial lesions (HSIL) on both Pap smear and biopsy.
About 21% of the women with a nor mal repeat Pap smear had high-risk HPV types. This rate exceeds but is not significantly higher than the 13% rate seen in the study's normal population. Among women with an abnormal repeat Pap smear, the rate was 54%.
All eight patients with underlying highgrade lesions tested positive for HPV: One had a low-risk HPV type, the others had a high-risk HPV type. All HPV negative patients were free of high grade lesions.
However, a high percentage of patients who tested positive for high-risk HPV were found to be free of high-grade lesions. Among the 208 ASCUS samples, 30% were positive for high-risk HPV, while only 4% proved to have HSIL on repeat Pap.
This study suggests that follow-up cytology alone, using the sensitive Thin Prep technique, may efficiently segregate ASCUS cases according to risk of progression to HSIL, Dr. Hughes said.
"That is the major criticism I have about rushing to use [HPV testing] in the general population," said Dr. Christopher Crum, a coinvestigator in the study and a professor of pathology at Harvard Medical School, Boston.
"Of all the women who will test positive for HPV, many will not develop any cancer. For that reason, when you test women you must have very well-placed mechanisms and safeguards to make sure you don't alarm large numbers of women who are HPV positive," he told this newspaper.
Dr. Hughes' paper was criticized by her discussant Dr. Walter Kinney, who declined to provide further comment for this article. Dr. Kinney, who works for Kaiser Permanente in Oakland, Calif., was concerned about the added cost of bringing a patient back for a second Pap smear.
The idea behind an HPV test as a screening tool is that the sample can be taken at the time of the initial Pap smear but only read if the Pap smear result comes back as ASCUS. So rather than bringing back all ASCUS patients for a second smear, only those with a positive HPV test need be brought back, Dr. Kinney said.
On the other hand, said Dr. Crum, "Our concern is that a large number of HPV-positive patients who are not going to develop cancer may be worried unnecessarily and possibly overmanaged by their physician."