HPV Testing Proves Sensitive in Identifying ASCUS Abnormalities That May Lead to Cervical Cancer

National Cancer Institute
Thursday, 23 March 2000

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 (short for atypical squamous cells of undetermined significance). Preliminary findings from a large randomized study show that HPV testing is highly sensitive in detecting the underlying abnormalities at risk for progressing to cervical cancer.

What to do about ASCUS has been a major issue in cervical cancer screening. Most of these mild abnormalities will go away without treatment. But physicians have had no way to tell which will go away and which will progress to a precancerous condition or cancer. One objective of the National Cancer Institute's ASCUS/LSIL Triage Study, or ALTS, was to determine whether HPV testing could sort out which women with ASCUS Pap smears need immediate attention and which do not.

The HPV test identified about 96 percent of the ASCUS cases that were found in colposcopy to be at risk of progressing to cancer (lesions categorized as CIN2 or CIN3). The ALTS investigators conclude that the HPV test is very sensitive at detecting ASCUS lesions that need immediate attention.

About 5 percent of women with ASCUS Pap tests were found to have underlying precancer or cancer. Because virtually all were detected by HPV testing, the finding of no HPV was highly reasurring in this population.

ALTS included about 5,000 women with mildly abnormal Pap tests. About two-thirds had ASCUS and about one-third had a somewhat more advanced abnormality called LSIL, or low-grade squamous intraepithelial lesion. Within each of these categories, women were assigned randomly to either immediate colposcopy (examination with a magnifying instrument), conservative management (the wait-and-see approach), or HPV testing. In the HPV group, women with positive HPV tests were sent to colposcopy and those with negative HPV tests were followed with repeat Pap tests.

Although the test has proved highly sensitive, improvements are needed in specificity -- that is, the test identified many ASCUS cases that were not CIN2 or CIN3 and probably would not progress to cancer. Further analyses will examine methods to improve specificity without sacrificing sensitivity.

"We still need to find the optimal way to use HPV testing,"said the National Cancer Institute's Diane Solomon, M.D., who presented these findings at the biennial meeting of the Society for Colposcopy and Cervical Pathology in Orlando, Fla., on March 16. "However, these results indicate that HPV testing is an option for women and their doctors to consider when deciding what to do about ASCUS."

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