On April 7, the New York Times published the story, “DNA test outperforms Pap smear.” This story summarized a New England Journal of Medicine article about the success of a large clinical trial in India that used a test for human papillomavirus to detect cases of cervical cancer, a major killer of women in countries with low screening resources. The results showed that HPV testing outperformed more traditional cervical cytology methods in this setting. However, the implication of this commentary could lead the reader to think that such a test might immediately supplant cytologic screening in countries with well-developed screening programs, such as the United States.
While HPV testing is highly sensitive (meaning it detects most cases of cervical cancer or its precursor lesions), it lacks specificity for that disease (meaning that many positive results do not indicate significant lesions). A positive test without the disease present is known as a “false-positive.” False-positives can lead to over-treatment, which may lead to complications that may increase the risk for other problems, such as infertility. The Indian study indicated that screening should not begin until age 30 because of the high number of false-positive tests in women under age 30. This screening scenario favors detection of well-established cancers, ignoring the fact that some cases of cervical cancer, particularly those that arise in the endocervical canal, may occur before age 30. These results do make very good public health sense for a country with low resources. This tradeoff in disease detection is necessary where there is no infrastructure for cervical cytology, trained screening professionals do not exist, money for screening is scarce, and preventing as many cases as practical is the goal. However, where well-established cervical cytology screening exists, making maximal use of that resource can ensure lower cervical cancer death rates than were achieved in this study.
In a commentary accompanying the New England Journal of Medicine article, Mark Schiffman, MD, MPH, and Sholom Wacholder, PhD (both noted researchers from the U.S. National Cancer Institute), write, “In developed nations, HPV testing at extended intervals could eventually replace repeated cytologic testing as the primary screening method.” They go on to say that other factors will be important in transforming this practice, including creating a sensitivity among the medical community to over-treatment of HPV-positive individuals and altering medical models of the frequency of gynecologic well-care visits, currently centered on the need for annual Pap testing.
The College of American Pathologists, as well as other major medical professional organizations, continues to advocate for annual cytology screening, with the addition of HPV testing in certain circumstances shown to be cost-effective in the U.S. population of women over age 30, and for followup of inconclusive cytology test results, as well as lengthening screening intervals only in circumstances of a series of confirmed prior negative examinations. Studies have shown that the use of these tests in these combinations achieves optimal cancer prevention rates in countries that have such resources available.
—Jared Schwartz, MD, PhD
As of CAP TODAY press time, the letter had not been published.