TESTING METHOD MAY BE CULPRIT BEHIND ABNORMAL PAP
TEST RESULTS
COLUMBUS, Ohio – Women who take oral contraceptive pills may get
an inaccurate and higher rate of false positive results if their
physicians use a specific kind of Pap test.
Pathologists at Ohio State University re-checked the Pap smears
of 84 women whose initial Pap results were diagnosed as abnormal
using the ThinPrep testing method. All women were on an oral
contraceptive. In each case, the cells lining the cervix looked like
cells infected with the sexually transmitted human papillomavirus
(HPV), a leading cause of cervical cancer.
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Gerard Nuovo
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The new diagnoses found that in two-thirds of the women, there
were no abnormal cervical squamous cells, or, more precisely,
atypical squamous cells of undetermined significance (ASCUS)/favor
low-grade dysplasia. The presence of dysplasia – abnormal cells –
indicates that a woman is infected with HPV, said
Gerard Nuovo, the study’s lead author and a professor of
pathology at Ohio State University.
“That’s a lot of women who were told that they had a venereal
disease but really didn’t,” he said. “Not only that, but HPV is also
a precursor of cervical cancer. We don’t see cases of cervical
cancer without the virus present.”
The study appears in a recent issue of the journal
Cancer Cytopathology.
He advises
women who test positive for ASCUS (atypical squamous
cells of undetermined significance) to request that
either a second pathologist re-check her Pap test
results or that she undergo testing for HPV.
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When diagnosing a Pap culture, pathologists look for
irregularities in cervical squamous cells. Squamous cells line the
surface of an organ.
The faulty Pap smears were originally diagnosed using the
ThinPrep Pap test, a fairly common test that filters out red blood
cells and inflammatory cells in a Pap smear, making it much easier
for pathologists to see any abnormalities in cervical squamous
cells. Nuovo believes that it’s the nature of the ThinPrep testing
method – a high-pressure system that filters out unwanted cells –
that changes the physical appearance of healthy squamous cervical
cells to look like cells infected with HPV.
Nuovo and his colleagues reviewed six months’ worth of ThinPrep
Pap test data from nearly 1,000 women on oral contraceptives. They
compared the rates of ASCUS/favor low-grade dysplasia detection in
this group to the ASCUS rates in more than 1,200 Pap smears from
women not taking birth control pills. The reported rate of
ASCUS/favor low-grade dysplasia among women taking an oral
contraceptive was more than twice that of the women not taking birth
control pills (9 percent vs. 4 percent).
“That’s a huge difference,” Nuovo said. “It meant that either
oral contraceptives put a woman at higher risk for developing
abnormalities in her cervix, or that the testing method was somehow
causing healthy cells to mimic virus-infected cells.”
Going with the latter theory, the researchers went a step further
and re-analyzed the ASCUS Pap smears from the women in the oral
contraceptive group. The specific kinds of oral contraceptives the
women used weren’t named in the study. The researchers used a
testing method that tested specifically for the presence of HPV in
cervical squamous cells.
They found that just 33 percent of the 84 Pap smears that had
originally tested positive for ASCUS actually contained abnormal
cells.
“This relatively low detection rate suggests that apparently
abnormal cervical cells in most young women taking oral
contraceptives really only mimic HPV infection,” Nuovo said. “The
ThinPrep test was causing changes in the cells that we had never
seen before with a conventional Pap test.”
While the healthy and infected cervical cells were similar in
shape and size, the key to detecting HPV infection resided in the
area surrounding the cell nucleus. In infected cells, this space was
clear; in healthy cells, the area was slightly cloudy.
Nuovo thinks that it’s the high-pressure filtration system used
by the ThinPrep Pap test that flattens out healthy cervical squamous
cells, changing their shape to resemble those that look like the
flat, round cells infected with HPV. However, there are subtle
differences between a healthy and an HPV-infected cell; for one,
healthy cervical cells have a glassy, opaque look, while infected
cells are clear. A well-trained pathologist should be able to make
the distinction, Nuovo said.
He advises women who test positive for ASCUS to request that
either a second pathologist re-check her Pap test results or that
she undergo testing for HPV. Such tests run from about $50 to $150
and insurance generally covers most of the cost, Nuovo said. He also
suggests that a woman ask her doctor which Pap testing method the
lab uses.
Few gynecologists use conventional Pap testing methods these
days, Nuovo said, simply because the conventional tests require
pathologists to look through countless red blood cells and
inflammatory cells trying to find squamous cells. Newer testing
methods such as ThinPrep eliminate this hassle.
Nuovo and his colleagues currently use a Pap testing method that
uses gravity instead of high pressure to separate out unwanted
cells.
“We haven’t seen the same kind of physical changes in the
cervical squamous cells that we saw when using the ThinPrep test,”
he said.
Nuovo conducted this study with Carl Morrison, Patricia Prokorym,
Clara Piquero and Paul Wakely, all with the department of pathology
at Ohio State.
A grant from the Lewis Foundation supported this work.
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Contact: Gerard Nuovo; 614 293 7853; Nuovo.1@osu.edu
Written by Holly Wagner, 614-292-8310; Wagner.235@osu.edu |
