Position Paper In The Journal Science Urges Restraint
In Using HPV/DNA Testingto Prevent Cervical Cancer

Hershey, PA--In an article published in the June 9 issue of Science, Joanna Cain, M.D., and Mary K. Howett, Ph.D., comment on the use of a recently released test that detects the presence of human papillomavirus (HPV), which can be a precursor to cervical cancer. Cain, professor and chair, Department of Obstetrics, and Howett, professor of microbiology and immunology, both at Penn State's College of Medicine, take the position that patient education, consistent availability of a Pap test as a screen for cervical cancer and appropriate follow-up are paramount for preventing cervical cancer.

The standard screening test for detecting cervical cancer remains the Pap smear. Introduced in 1950, this test can detect pre-malignant changes in the lining of the cervix. Between 1955 and 1992, the American Cancer Society estimates a 74% decline in the incidence of invasive cervical cancer in the United States as a result of Pap test screening and early intervention. There is now compelling evidence that HPV, a sexually transmitted disease, increases the risk of pre-malignant lesions and progression to cervical cancer. The recently released HPV DNA test identifies the presence of some types of HPV in a woman's cervix.

"The link between HPV and cervical cancer requires clarification," says Cain. Although 99.7 percent of cervical cancers are linked to HPV, only 1 percent of woman who have HPV go on to develop cervical cancer." There are more than 100 HPV subtypes of which 20 have oncogenic (cancer producing) potential. The HPV DNA test, an extremely sensitive assay, can identify the virus in a latent stage when there is no evidence of cervical disease.

Cain and Howett point out limits to the use of that HPV DNA testing as a screening tool. Although a positive HPV test confirms the presence of a virus, it does not confirm actual disease. For that reason, a positive HPV DNA test yields more false positives when used as an indicator of cervical disease. That, say the authors, has significant social consequences. A positive test result could leave women with a social stigma, as well as the worry about developing cancer. Cain cautions that this means that women could be either over-treated at a young age or under served because a negative result gives a sense of false security. "There should be a strong cautionary note in the propulsion of HPV testing into the mainstream of cervical cancer screening," she says.

The HPV DNA test has been introduced in the United States, Europe and Asia as an adjunct to the Pap screen when the Pap smear shows atypical squamous cells of undetermined significance (ASCUS). Cain, a gynecologic oncologist whose practice centers women with gynecologic cancer, says that conducting an HPV DNA test doesn't presently change follow-up care for patients. Potential changes in follow-up may be if the Pap test shows ASCUS and HPV DNA tests are negative. "We also have no idea about frequency and timing of this test with regard to effectiveness and a negative test result is no guarantee that a woman will not get cervical cancer, " she says. "Failure to get a Pap smear is the No. 1 factor related to women getting cervical cancer."

In addition to HPV DNA testing, the use of microbicidal agents that kill HPV and vaccines to protect against HPV infection are new strategies to detect and prevent cervical cancer. The longevity of the immune response to vaccineØthe vaccine's effectiveness over timeØis unknown. If a vaccine prevents certain HPV subtypes from infecting a woman, it is possible that other subtypes will quickly fill the void.

Howett's research has identified the first microbicidal drugs that can block or inactivate papillomavirus. Howett hopes this work will lead to a product that will block transmission of HPV. She says that topical microbicides are practical, female-controlled and inexpensive. "They may be especially useful in developing countries where vaccine delivery is economically challenging. As with any other treatment, they must be culturally acceptable and coupled with education to encourage use," she adds.

In the conclusion to the paper, Howett and Cain emphasize that education of the general public and cost effectiveness are keys to success for new strategies to prevent cervical cancer. HPV/DNA testing may reduce cost by identifying a low-risk group for less frequent screening, but there is no proof that the savings from HPV testing are greater than the expense associated with increased screening of women identified by a positive HPV test as high risk.

"Also, Pap smears are already underused," says Cain. "In the US, the majority of women diagnosed with cervical cancer have not had a Pap smear within three years. Right now the primary concern should be getting women to use Pap screening worldwide with adequate access to care for women with positive Pap smears."

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