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.
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.
Contact: Gerard Nuovo; 614 293 7853; Nuovo.1@osu.edu
Written by Holly Wagner, 614-292-8310; Wagner.235@osu.edu
Journal
Cancer Cytopathology