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
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
"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
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
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