Researchers led by Diane Solomon, MD, a senior investigator at the National Cancer Institute, studied 3,488 women, comparing existing options for evaluation after an uncertain Pap test result with a test that detects the presence of some strains of the human papillomavirus (HPV) known to cause cervical cancer. Because more than 95% of cervical cancers are caused by HPV infection, the absence of the infection identifies women who are not at risk for cancer.

"This study shows HPV testing can be used as a supplement to Pap tests when Pap test results are uncertain," Solomon says. "It can help a woman and her doctor to decide if further follow-up is necessary."

Women are encouraged to have an annual Pap test, in which a sample of cells from the cervix is examined under a microscope to detect any changes that could lead to cancer. After three or more consecutive normal results, a woman and her physician may consider less frequent testing. Results from the Pap test are classified in one of the following categories:

• normal
• reactive changes (a response of cells to an infection or other irritation)
• atypical squamous cells of undetermined significance (ASCUS)
• squamous intraepithelial lesion or SIL (potentially precancerous), or
• cancerous.

When cells are judged to be in the uncertain category, or ASCUS, doctors usually use one of two options for further evaluation or treatment.

One option is an immediate colposcopy (exam with an instrument that visually magnifies the cervix) and removal of any areas likely to be precancerous or cancerous. A second option is to repeat the Pap test later and proceed to colposcopy only if the second test shows more abnormal cells that might need removal.

Both options are useful but have disadvantages. A colposcopy is expensive and uncomfortable, so it should only be given if necessary, and a repeat Pap test can miss some cases of potentially precancerous changes.

When the researchers looked at the value of using the presence of high-grade precancerous changes in a repeat Pap test (without an HPV test) to indicate whether a woman should then receive a colposcopy, they found that 63.9% of the women who truly needed a colposcopy would not have had one.

When the presence of lower grades of precancerous changes found on a second Pap test were used to decide who did and did not get a colposcopy, 14.7% of women who truly needed that test would not have had it done.

But testing for HPV identified almost all (96.3%) of the cases of ASCUS involving precancerous changes that had the possibility of developing into cervical cancer. And because only 58.6% of the women with ASCUS had a positive HPV test result, almost half of women with uncertain Pap results were safely spared the discomfort, expense, and concern associated with a colposcopy. Those who needed one could get it quickly.

Thus, testing for dangerous strains of HPV was the best way to decide which women with ASCUS truly needed further follow-up by colposcopy.

"If the HPV test comes back negative, ? that can provide a lot of assurance for the woman," says Solomon. "If the HPV test is positive, it does not necessarily mean she has a precancerous condition. It means she needs further follow-up to see if there is an abnormality that needs treatment."

Solomon emphasizes that HPV testing is not the only option or always the best option for clarifying results of uncertain Pap tests. If a woman has had previous abnormalities, she and her doctor may decide it would be best to proceed directly to a colposcopy, Solomon says.

"A woman should be aware and informed of what her options are and discuss them with her doctor, and together they should decide on what step is best for her in her individual case," she says.

An American Cancer Society-affiliated expert says the HPV test is a useful one for several reasons. "This study shows that HPV testing can be a very valuable tool in helping clarify uncertain Pap test results," says Debra A. Bell, MD, director of the cytopathology laboratory at Massachusetts General Hospital in Boston, and a member of the ACS advisory board on gynecologic cancers.

"The test is a really good option when there?s a strong desire to get an immediate answer about whether you should go to colposcopy, rather than waiting several months before a second Pap test, and is very good at identifying women who do not have high-risk disease or cancer," says Bell.

Bell adds that cost-benefit analyses haven?t been done on this test, so it is yet to be determined how expensive it will be compared with other options. In addition, the test is not yet available everywhere.

Both doctors emphasize the need for women to get Pap tests on a regular basis, saying that without that first step, there is little chance of preventing cervical cancer or finding it early enough to treat successfully. For more information about cervical cancer screening, click here.