New studies are showing that the 60-year-old Pap test, “the best screening tool ever introduced for any cancer,” has competition or, at least, a companion. Two separate studies are affirming that a DNA test, the HPV test, better identifies cervical cancer and high grade (grades 2 and 3) cervical intraepithelial neoplasia (CIN), a lesion that can progress to cancer. (The higher the grade, the more likely the lesion will progress to cancer.) Published in the October 18 issue of the New England Journal of Medicine, these large studies add evidence on the value of screening for human papillomavirus (HPV) in women over age 30. Younger women were not studied because they have more cases of HPV infections that resolve on their own and do not develop into cancer.

One study was conducted in Sweden and the other in Canada. Both found the HPV test to be a valuable first-line screening tool.

The Swedish Study:
Pap + HPV Test
The Swedish study examined whether using the HPV test and Pap test (also known as a Pap smear or cervical cytology test) together provides better long-term protection against cervical cancer for women in their 30s compared to using the Pap test alone.

The researchers screened one group of women using both a very sensitive HPV test (one not widely available) and the conventional Pap test (not the liquid-based one most often used in the United States). A second group received screening using only the conventional Pap test. At the start of the study and again at subsequent screening, the researchers measured the number of cases of high-grade CIN or cancer found in each group.

The authors concluded that HPV testing helped diagnose problematic lesions earlier. At the time of initial testing, 51 percent more cases of CIN or cervical cancer were found in the women receiving both tests (appropriate treatment was offered to all women who tested positive). At the subsequent test, women who had received both tests initially had 42 percent fewer cases of CIN or cervical cancer, indicating that the earlier screening had been more effective when both tests were used.

Using both tests may allow the interval between tests to be longer, the authors noted. Many women get tested less often than recommended (see Notes below), and they might benefit from the longer protection. Using both tests may lead to fewer deaths from cervical cancer in these women, the authors suggested.

A downside is that using both tests raises upfront costs. The dual approach may not be a good solution in screening programs in resource-poor countries, an editorial in the same issue of the journal noted. The editorial also pointed out that for women in the United States, the advantages of using both tests may be less than the Swedish study showed. In the States, a liquid-based test, which is more sensitive than the conventional Pap test in some situations, is widely used.

The authors pointed out another concern in using the tests together: more grade 2 CIN cases were found than when using repeated Pap tests. Grade 2 CIN is less likely to progress to cancer than is grade 3, so screening with both tests may have led to unnecessary treatment of some women. Future studies might distinguish between grades 2 and 3, they suggested, preventing overdiagnosis of grade 2 lesions that might never develop into cancer.

The Canadian Cervical Cancer Screening Trial:
Pap vs HPV Test
The Canadian study asked if testing for HPV viral DNA is a better way to screen for cervical cancer than looking for abnormal cells via a Pap test.

The randomized trial included 10,154 women aged 30 to 69 from 30 clinics in Montreal and St. John’s, Canada. Those studied were women “at average risk for cervical cancer who had access to quality care,” explained the editorial discussing both studies in the same issue of the journal. The women received both tests, but in different order, depending on their assigned group.

The researchers found that the HPV test detected 94.6 percent of cases of high grade CIN, whereas the Pap test they used found only 55.4 percent. False-positive results were only slightly (2.7%) more common with the HPV test than for the Pap test. False positives are a concern because they expose patients to additional risks, which can include unnecessary testing and invasive medical procedures, as well as more expense and worry.

A New Era
An editorial in the same issue of the journal pointed out advantages of the HPV test: the test is highly reproducible, easily monitored, and objective. Pap tests not only sometimes miss abnormal cells, but they require highly trained personnel and specialized equipment. The HPV test uses automated equipment, is less labor-intensive, and less prone to error. A much-talked about advantage is that the HPV test may not need to be done as often as the Pap test. The HPV test may, thus, be better for those with less access to screening programs, the editorial suggested.

The editorial also noted that both of these studies compared the HPV test to the conventional Pap test, not the liquid-based Pap smear most often used in the United States. A large study comparing the HPV test to the liquid-based test is underway.

At present, the FDA has not approved the HPV test to be used by itself to screen for cervical cancer. In 2003, the FDA approved the HPV test for use along with the Pap smear for women over age 30.

These studies build a strong case for HPV testing. With the availability of the HPV vaccine and HPV test, the Canadian researchers noted, we are in a “new era of cervical cancer prevention.” These tools enable a more efficient way of diagnosing cervical cancer. Talk to your health care provider about what changes might be appropriate in your care. Take time to understand that the HPV test may help to identify precancer and early cancer. Some questions to ask:

Should you receive the HPV test in addition to a Pap smear?

At your age, which test or tests seem best?

How will your health care provider guide you through the follow-up and any additional testing or medical procedures recommended if a test is positive?

Will your health care provider notify you if the test is negative or do you need to follow up and contact them for the results?

Most importantly, get tested. These screening tests are the best way to protect yourself against cervical cancer.

Notes

The American Cancer Society estimates that more than 11,150 cases of cervical cancer will be diagnosed in the United States in 2007 and 3,670 women will die of the disease this year.

Sixty percent of the women diagnosed with cervical cancer in the United States have never had a screening test to look for the disease, at least not in the 5 years before they were diagnosed.

Sources

S1
Runowicz, CD. 16 Oct 2007. Molecular screening for cervical cancer—time to give up Pap tests? (editorial). New England Journal of Medicine 357(16):1650-3.

S2
Naucler P et al. 18 Oct 2007. Human papillomavirus and Papanicolaou tests to screen for cervical cancer. New Engl J Med 357(16):1589-1597.

S3
Mayrand M-H et al. 18 Oct 2007. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. New Engl J Med 357(16):1579-1588.