NIH Press Release
NATIONAL INSTITUTES OF HEALTH
National Cancer Institute

FOR IMMEDIATE RELEASE
Thursday, Jan. 30, 1997
4:00 PM Eastern Time

NCI Press Office
(301) 496-6641

NCI Launches National Study of Abnormal Pap Tests
in Cervical Cancer Screening

The National Cancer Institute (NCI) is launching a large national study to answer one of the most controversial questions in women's health: What should women and their physicians do about the mild abnormalities that often show up on Pap tests? The results could affect the 2 to 3 million American women each year who learn that their Pap test -- the routine screening test for cervical cancer -- has uncovered a mildly abnormal change in cells lining the cervix.

The new trial will evaluate three different ways of managing these abnormalities: 1) colposcopy -- a procedure in which a physician examines the cervix through a magnifying instrument and biopsies any abnormal areas; 2) repeating the Pap test every six months (because most abnormalities return to normal without treatment); and 3) testing for certain types of human papillomavirus (HPV), as a means to differentiate between abnormalities that need immediate colposcopy and those that can be best followed with repeat Pap tests at six-month intervals.

Each year, Pap tests reveal serious, precancerous abnormalities called HSIL (high-grade squamous intraepithelial lesions) in about 300,000 women in the United States. There is little controversy about the management of HSIL; it must be treated to prevent cervical cancer. However, no consensus exists on the way to manage the far more common, milder abnormalities known as ASCUS (atypical squamous cells of undetermined significance) and LSIL (low-grade squamous intraepithelial lesions).

At present, many physicians recommend immediate colposcopy and biopsy for ASCUS and LSIL. This is because the mild abnormalities may, in a small proportion of cases, indicate the presence of HSIL or risk of progression to HSIL. However, most abnormalities will return to normal without treatment.

"We may be overtreating these mild abnormalities in many cases," said Diane Solomon, M.D., one of the study's project officers at NCI. "The new trial will determine whether physicians can safely take an approach that is less aggressive. If so, millions of women could avoid colposcopy and biopsy each year." The trial tests two major hypotheses. One is that follow-up with repeat Pap tests is a safe and effective way to manage ASCUS and LSIL. The second is that HPV testing can help in managing these mild abnormalities.

Most true abnormalities on Pap tests are the result of HPV infection, according to NCI's Mark Schiffman, M.D., the study's co-project officer. However, there are many types of HPV. Of the more than 70 known types, less than half infect the cervix, and not all of the types found in the cervix are the high-risk types that have been linked to HSIL and cancer. The trial is designed to determine whether HPV testing can help predict which women are at higher risk of HSIL and thus need to undergo colposcopy.

In addition to testing these two hypotheses, the trial will explore several other issues. Researchers will compare the cost-effectiveness of each of the three management options. They also will gather data on how acceptable each strategy is to women and how it has affected their lives.

The trial will, in addition, investigate immune-system factors that may help determine the course of HPV infections; folate levels and their relationship to cervical lesions; and strategies for recruiting and retaining minority women in clinical studies.

To make sure that they do not miss any serious precancerous abnormalities or cancer, trial organizers have built in a number of safeguards. At the beginning of the trial and at each follow-up visit, all participants will have a cervigram -- a magnified photograph of the cervix -- which will be read by certified expert evaluators. Any participant whose cervigram is worrisome will have an immediate colposcopy. As another safeguard, three different quality control groups will monitor the results of the various tests and procedures used in the study. In addition, all participants will have colposcopy at the end of the study to ensure that no serious abnormalities have been missed.

The $20 million study, known as ALTS (ASCUS/LSIL Triage Study), will enroll about 7,200 patients with mild Pap test abnormalities. The four ALTS centers are the University of Alabama at Birmingham (Birmingham, AL); University of Oklahoma (Oklahoma City, OK); Magee-Womens Hospital (Pittsburgh, PA); and University of Washington (Seattle, WA).

ALTS researchers plan to complete enrollment in 1998; all participants will be followed for about three years.

Approximately 15,000 American women are diagnosed with cervical cancer each year and about 5,000 die of the disease. In areas of the world where Pap tests are not widely available, cervical cancer is a leading cause of cancer deaths in women. Regular Pap tests are the key to preventing this disease, according to experts at an NIH conference held in April 1996.

NOTE TO REPORTERS: A backgrounder on ALTS and HPV infections and a graphic showing the prevalence of Pap test abnormalities is available; call the NCI Press Office at (301) 496-6641.


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