Testing for the human papillomavirus (HPV) may help doctors and patients decide what to do about the mildly abnormal and very common Pap test result known as ASCUS. Findings from a major, randomized, multicenter study by the National Cancer Institute (NCI) show that HPV testing is highly sensitive in identifying which Pap-detected abnormalities require immediate attention.
A report on the trial, which is known as the ASCUS/LSIL Triage Study or ALTS, appears Feb. 21 in the Journal of the National Cancer Institute. ASCUS and LSIL are acronyms for two mild abnormalities detected by Pap tests. One objective of ALTS was to determine whether HPV testing could sort out which women with ASCUS Pap test results need immediate attention and which do not.
What to do about ASCUS (short for atypical squamous cells of undetermined significance) has been a major issue in cervical cancer screening. Most of these mild abnormalities will go away without treatment. But physicians and patients have had no way to tell which will go away and which represent more serious conditions -- precancer or cancer -- that need to be treated.
In this study, HPV testing identified virtually all (96.3 percent) of the ASCUS abnormalities that needed treatment. "These results indicate that HPV testing is a viable option for women and their doctors to consider when deciding what to do about ASCUS," said NCI's Diane Solomon, M.D., principal investigator of ALTS.
Although the HPV test proved highly sensitive, Solomon noted that the other two approaches to ASCUS remain options to consider. These are immediate colposcopy (examination with a magnifying instrument) with biopsy if indicated or follow up by repeat Pap tests every six months. Patients and physicians may take several factors into account when deciding what to do about ASCUS, such as cost and patient preferences regarding follow-up appointments. The ALTS investigators plan to analyze the cost effectiveness of the three options when long-term data from the study become available.
Data from ALTS and other cervical screening studies will be evaluated by medical groups at two upcoming conferences, which are being convened to consider screening and management guidelines. NCI is convening the first of these, the Third Bethesda Workshop, April 30 - May 2, in Bethesda, Md., to address the diagnosis and reporting of Pap test results. The second, led by the American Society for Colposcopy and Cervical Pathology, will develop evidence-based guidelines for clinical practice. It will take place in Bethesda, Md., Sept. 6-9.
ALTS included about 5,000 women with mildly abnormal Pap tests. About two-thirds had ASCUS and about one-third had the more definite abnormality called LSIL, or low-grade squamous intraepithelial lesion. Within each of these categories, women were assigned randomly to three different groups. One group had an immediate colposcopy – a procedure in which a physician examines the cervix through a magnifying instrument and biopsies any abnormal areas. A second group had repeat Pap tests. The third group was assigned to HPV triage. In this triage group, patients' Pap specimens were tested for HPV types associated with cervical cancer. Those who were HPV-positive had an immediate colposcopy and biopsy and those who were
HPV-negative did not.
For the current study, the investigators analyzed the ALTS data from women who had been referred to colposcopy when they enrolled in the trial. The colposcopy results were compared to the results of HPV tests that patients also had on enrollment. The colposcopy results showed that about 5 percent to 10 percent of women with ASCUS had precancer or cancer and that, of these women, 96.3 percent had a positive HPV test. As a corollary,
99.5 percent of women with a negative HPV test did not have precancer or cancer.
The investigators conclude that HPV testing can help in deciding what to do about ASCUS. "A positive test suggests that precancer or, rarely, cancer may be present -- we found precancers in 10 percent to 20 percent of ASCUS cases in which the HPV test was positive," said NCI's co-principal investigator, Mark Schiffman, M.D. "A negative test provides strong reassurance that precancer or cancer is not present."
About 55 percent of women with ASCUS would have been referred to colposcopy if the HPV test had been used for triage in all cases. Thus, HPV testing reduced referrals to colposcopy by about a half compared to immediate colposcopy.
ALTS was conducted at four major medical centers: the University of Alabama at Birmingham; the University of Oklahoma in Oklahoma City; Magee-Womens Hospital of the University of Pittsburgh Medical Center in Pittsburgh, Pa.; and the University of Washington in Seattle. It was organized and funded by the NCI, which is the US government's principal agency for cancer research.