Get ready to take cervical cancer screening to the next level

Newly approved human papillomavirus test offers 2-in-1' package

When it comes to the fight against cervical cancer, clinicians can count themselves on the front lines of the battle. It is estimated some 50 million women in the United States are screened on an annual basis with Pap tests.1 Such effort is warranted: In 2003, the Atlanta-based American Cancer Society (ACS) estimates some 12,200 women will be diagnosed with cervical cancer, and 4,100 will die from the disease.1

Clinicians now have another tool in their arsenal with the Food and Drug Administration’s (FDA) approval of a new screening test that will help distinguish women at increased risk of developing the disease from those at very low risk. The DNAwithPap, manufactured by Digene Corp. of Gaithersburg, MD, combines the company’s existing Hybrid Capture 2 High-Risk HPV (human papillomavirus) DNA test with a Pap test.

The FDA approved the new dual test as a primary screening option for women 30 years of age and older. The new test is not intended to substitute for regular Pap screening, nor is it intended to screen women younger than 30 who have normal Pap tests, states the FDA.1

Information on the dual test already is included in the ACS’s new screening guidelines, which were released in November 2002, says Debbie Saslow, PhD, director of ACS’s breast and gynecologic cancer programs. The ACS guidelines call for Pap tests beginning either at age 21 or three years after a woman first has sexual intercourse.2 Until age 30, screening should be done every year with the regular Pap test or every two years using the liquid-based Pap test. After age 30, women who have had three normal Pap tests in a row can wait two or three years for their next Pap.

Women with a negative HPV test and a normal Pap smear need not be screened again for three years. Women with a positive HPV test and a normal Pap test should be retested in six months to a year.

The addition of an HPV test to cytology screening will allow women to extend screening intervals to three years with greater confidence, says George Sawaya, MD, assistant professor of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco, who conducted some of the research on which the three-year screening interval was based.3 It is important to realize, however, that many women with a history of normal Pap smears can do so safely without adding this new test, he notes.

"Women and clinicians need to be thoughtful about the true benefits and potential downsides of adopting this new strategy so that good, informed decisions can be made," observes Sawaya. "The main concern is the uncertainty around the appropriate management of women who test positive for HPV DNA, but who have a normal Pap test."

Digene Corp. plans a full-scale launch of the new test in the third calendar quarter of this year, says Charles Fleischman, company president. Digene is working actively with payers so that widespread coverage and payment for HPV testing quickly becomes available for DNAwithPap, he reports. Nearly all health plans cover the $50 HPV test for women with mildly abnormal Pap tests; with FDA approval of wider use, Digene Corp. looks to insurers to follow suit.4 Digene’s test will cost $50-$60, compared with $14-$30 for a Pap-only test.5

About 50% of U.S. women with atypical squamous cells of unknown origin (ASC-US) Pap test results are tested with Digene’s hc2 HPV Test, according to Digene Corp.; 270 laboratories offer the testing, it states. Reimbursement for the ASC-US indication is available for approximately 90% of the U.S. population with health insurance, the company estimates.

Digene Corp. is launching an educational campaign to inform clinicians and women about the availability of the DNAwithPap as a primary screening test for women older than age 30, says Fleischman. Other organizations, such as the American Cancer Society, also are developing information campaigns for clinicians and women, he says.

Clinicians are familiar with the HPV screening technology, which can detect 13 high-risk types of HPV. Since March 2000, the test has been used for women with ASC-US test results.2

Studies have shown the effectiveness of the testing,6,7 and screening with HPV plus Pap tests appears to save additional years of life at reasonable costs compared with Pap testing alone.8 Research indicates that reflex HPV DNA testing provides the same or greater life expectancy benefits and is more cost-effective than other management strategies for women diagnosed as having ASC-US.9

Who should be tested?

Up to 20% of the sexually active U.S. population is believed to be infected with HPV at any one time, states the FDA.1 Most women who become infected with HPV are able to eradicate the virus, but some women develop a persistent infection that eventually can lead to pre-cancerous changes in the cervix. Women who have normal Pap test results and no HPV infection are at very low risk (0.2%) for developing cervical cancer.1 Women who have an abnormal Pap test and a positive HPV test are at a 6%-7% increased risk of developing cervical cancer if not treated.1

The risk of HPV progressing and causing changes that could lead to cancer is greater for women older than age 30 than for younger women, says Saslow. HPV infections in younger women tend to go away by themselves. In women older than 30, if an HPV infection has not cleared in a year, clinicians will want to do additional testing and follow-up to see if further treatment is needed, she notes.

With news reports of the FDA approval, expect women to ask you about the availability of the new test. What should you tell them?

"Women can have the test if they want to, but they should not feel like they are missing out if they either decide not to have it, if their doctor does not offer it, or their insurance does not cover it," says Saslow. "The Pap test is still a good test."


For more information on HPV testing, contact: Digene Corp., 1201 Clopper Road, Gaithersburg, MD 20878. Telephone: (800) 344-3631 or (301) 944-7000. Fax: (301) 944-7121. Web:

The Atlanta-based American Cancer Society (ACS) has collaborated with other national professional organizations in developing a web-based fact sheet, "What Women Should Know about HPV and Cervical Health." To review the fact sheet, go to the ACS web site,; click on "Medical Updates," "Cervical Cancer," "FDA Approves New Cervical Cancer Screening Test," and "What Women Should Know about HPV and Cervical Health." The fact sheet is a work in progress with the most frequently asked questions from patients and providers. The organization encourages feedback from consumers, clinicians, and organizations; such information will be incorporated in a print version.


1. Food and Drug Administration. FDA approves expanded use of HPV test. Bethesda; March 31, 2003. Accessed at

2. American Cancer Society. FDA approves new cervical cancer screening test. Atlanta; March 31, 2003. Accessed at

3. Sawaya GF, Kerlikowske K, Lee NC, et al. Frequency of cervical smear abnormalities within three years of normal cytology. Obstet Gynecol 2000; 96:219-223.

4. Rubin R. Newly approved HPV test must be used wisely, experts say. USA Today, April 3, 2003: Accessed at

5. Barbaro M. Digene’s cancer test approved by FDA. Washington Post, April 1, 2003:E01.

6. Wright TC Jr., Denny L, Kuhn L, et al. HPV DNA testing of self-collected vaginal samples compared with cytologic screening to detect cervical cancer. JAMA 2000; 283:81-86.

7. Schiffman M, Herrero R, Hildesheim A, et al. HPV DNA testing in cervical cancer screening: Results from women in a high-risk province of Costa Rica. JAMA 2000; 283:87-93.

8. Mandelblatt JS, Lawrence WF, Womack SM, et al. Benefits and costs of using HPV testing to screen for cervical cancer. JAMA 2002; 287:2,372-2,381.

9. Kim JJ, Wright TC, Goldie SJ. Cost-effectiveness of alternative triage strategies for atypical squamous cells of undetermined significance. JAMA 2002; 287:2,382-2,390.