Popular Pap Test May Cause False Results

Birth Control Pills Might Make Healthy Cells Look Abnormal

From the WebMD Archives

July 9, 2003 -- Women who take birth control pills may be more likely to get inaccurate results indicating the presence of abnormal cells or early cancer of the cervix when their doctors use the most popular type of Pap test, suggests a new study.

In rechecking Pap smears of 84 women whose initial results were found to be abnormal with the ThinPrep smear, researchers found only a third of them had abnormal cervical cells suggesting they were infected with the human papillomavirus (HPV), a sexually transmitted disease that is a leading cause of cervical cancer. Two-thirds of the women were found not to have HPV.

All of the women evaluated in this study -- recently published in the medical journal Cancer Cytopathology -- were taking birth control pills. But the study's lead researcher tells WebMD that others may be vulnerable to get false positives from ThinPrep. The ThinPrep method of collecting samples from Pap smears has been found to be as good as, if not better than, the conventional Pap smear collection methods. And it is used by most doctors and about 80% of diagnostic laboratories.

Hormones the Culprit

"It's more common in women using birth control pills, but these false results can occur with any condition in which the woman had a predominance of certain types of female hormones -- pregnancy, taking hormone replacement therapy, and even being in certain phases of her cycle," says Gerald Nuovo, MD, professor of pathology and director at cytology at Ohio State University Medical Center.

Nuovo believes the inaccurate findings result from the nature of ThinPrep, which has gained in popularity in recent years because it is more sensitive than other tests at identifying cancerous cells. Along with the SurePath Pap test, ThinPrep is a newer, liquid-based preparation test. Rather than simply smearing the sample onto a slide, the collection device is rinsed in a vial and sent to the lab for the slide to be prepped and evaluated. .

"The problem with the older tests is that there were so much blood and inflammation in the smear that the pathologist couldn't see all the cells," Nuovo tells WebMD. "With ThinPrep and SurePath, that problem has been solved."

The Appearance of HPV

But unlike SurePath, Nuovo says the ThinPrep test uses a high-pressure system that, in filtering unwanted cells and debris, can change the physical appearance of healthy cells -- making them look as though they were infected with HPV and prompting test results suggesting the presence of atypical cells or a "false positive."

There are nearly 100 different types of HPV, and together they infect about 24 million Americans. About one-third are transmitted through sexual contact without a condom or diaphragm and while most are harmless, some cause genital warts and 14 strains are thought to cause at least 90% of cervical cancers.

In his study, Nuovo and his colleagues initially reviewed ThinPrep Pap tests from nearly 1,000 women taking birth control pills and compared the rates of atypical results with 1,200 women not taking oral contraceptives. The pill-takers had twice the rate of abnormal Paps test suggesting the presence of HPV.

"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," he says. Going on the latter theory, he re-analyzed the data on 84 Pap smears indicating HPV. Only one in three actually had abnormal cells.

Still the Top Test

Still, there's no reason not to continue to use ThinPrep, say two experts not involved in the study.

"This is an interesting observation," says William T. Creasman, MD, of the Medical University of South Carolina and a spokesman for the American College of Obstetricians and Gynecologists.

"What it may do is get the labs to look at their data and see if, in fact, this is a phenomenon that is universal or something unique in this particular group," he tells WebMD. "If it is something beyond this group, it could have some clinical implications because then you're doing a heck of a lot more than you need to because you have a lot of false positives."

Most women who currently have abnormal Pap tests are retested (often with the same type of smear), and/or given a specific HPV test or undergo a colposcopy, a visual examination of the cervix.

Kenneth Hatch, MD, chairman of obstetrics and gynecology at the University of Arizona College of Medicine and president of the Society of Gynecologic Oncologists, tells WebMD that despite the finding, the ThinPrep test will continue to be the Pap smear favored by most doctors.

"It's been a major breakthrough in cervical cancer screenings," he tells WebMD. "The majority of clinicians in the U.S. use ThinPrep because it offers increased sensitivity over others in identifying lesions."

"This is an observation that may or may not have bearing," says Hatch. "But like any observation, it needs to be verified before we say it is inherent of the test as opposed to the interpreter. All Pap tests are looked at by human eyes."

Show Sources

SOURCES: Cancer Cytopathology, April 2003. Gerald Nuovo, MD, professor of pathology and director of cytology, Ohio State University Medical Center, Columbus. William T. Creasman, MD, chairman emeritus and the Sims-Hester Professor, Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston; spokesman, the American College of Obstetricians and Gynecologists. Kenneth Hatch, MD, chairman and professor, Department of Obstetrics and Gynecology, the University of Arizona College of Medicine, Phoenix; president, the Society of Gynecologic Oncologists.
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