The first large-scale study of both human papillomavirus (HPV) testing and Pap test for cervical cancer screening in routine clinical practice confirms that women can safely extend their screening intervals from one to three years. The study also found that HPV testing may be more accurate than conventional Pap test in determining cervical cancer risk.

"Our results are a formal confirmation that the three-year follow-up is appropriate and safe for women who have a negative HPV test and normal Pap result," said lead author Hormuzd Katki, Ph.D., principal investigator in the Division of Cancer Epidemiology and Genetics at the National Cancer Institute. "These results also suggest that an HPV-negative test result alone could be enough to give a high level of security for extending the testing interval to every three years, but we'll need additional evidence from routine clinical practice, and formal recommendations from guideline panels before that can be routinely recommended."

Cervical cancer is caused by infection with HPV, which is sexually transmitted and can be detected by testing a sample of cervical cells for viral DNA. HPV infection is almost always cleared by the body, but if not, cancer may develop, typically decades after initial infection. While Pap testing has dramatically reduced cervical cancer rates, incorporating HPV testing into screening programs could reduce cancer rates even further. Screening guidelines from American medical organizations such as the American College of Obstetricians and Gynecologists (ACOG) and the American Cancer Society (ACS) have endorsed the use of concurrent HPV testing with Pap tests as a safe alternative to Pap testing alone for women 30 and older, recommending co-testing every three years for women who are HPV-negative and have a normal Pap test. However, co-testing has not been widely adopted by physicians and women, many of whom are unsure about the safety of extending testing intervals for more than one year. This study provides substantial data from routine practice confirming that the practice is safe.

In the study, researchers followed 331,818 women ages 30 and older who enrolled in Kaiser Permanente Northern California's co-testing program between 2003 and 2005 for five years. The researchers found that the five-year cancer risk for women who had both a normal Pap test and tested negative for HPV was very low: 3.2 per 100,000 women per year.

Looking at each test individually, HPV-negative women had half the cancer risk of women with a normal Pap test (3.8 per 100,000 women per year compared to 7.5 per 100,000), suggesting that HPV testing alone is more accurate than Pap testing alone, and that the cancer risk for HPV testing alone was similarly low, compared with HPV and Pap testing together (3.8 versus 3.2 per 100,000).

HPV testing also identified more women at high risk for cervical cancer than Pap tests. Women who tested HPV-positive at enrollment (regardless of Pap test results) had higher five-year risks of cervical cancer or pre-cancer than women with an abnormal Pap test at enrollment regardless of HPV test results (1.5 percent per year versus 0.9 percent per year). By finding, at enrollment, more women at risk for cancer, HPV testing facilitated earlier intervention to prevent cancer.

However, according to Dr. Katki, Pap tests remain important for determining which women who tested HPV-positive should have further screening. HPV-positive women who had an abnormal Pap test were more likely to have - or soon develop - cancer or precancer than HPV-positive women with a normal Pap test.