DNA Test Found More Effective Than Pap for Detecting CIN


Testing for human papillomavirus DNA, either alone or in addition to routine Pap screening, improves the detection of cervical intraepithelial neoplasia, two research groups reported in separate studies.

One of the groups of investigators also found that adding human papillomavirus (HPV) DNA testing to Pap testing also decreased the incidence of high-grade lesions and cancers found on subsequent screens over the next few years.

“This result indicates that the improved sensitivity of HPV testing is not merely due to overdiagnosis but is attributable, at least in part, to earlier diagnosis of lesions that do not regress,” they said.

In an editorial comment accompanying the two reports, Dr. Carolyn D. Runowicz of the University of Connecticut Health Center, Farmington, said that if additional studies confirm these findings, HPV DNA testing may eventually replace cytologic testing.

However, “we are not there yet,” she cautioned.

In the first study, Dr. Marie-Hélène Mayrand and her associates in the Canadian Cervical Cancer Screening Trial (CCCaST) directly compared HPV and Pap testing as stand-alone screens for cervical cancers and their high-grade precursors in more than 10,000 women aged 30–69 years who presented to 30 Canadian clinics for routine screening in 2002–2005. A total of 5,059 women were randomly assigned to undergo Pap testing followed by HPV testing, and the remaining 5,095 to undergo HPV testing followed by Pap testing.

Both tests were found to have negative predictive values higher than 99%.

However, HPV testing proved to be 39% more sensitive than Pap testing. This improved sensitivity was not achieved at the expense of drastically reduced specificity, as HPV testing was only 2.7% less specific than Pap testing, said Dr. Mayrand of McGill University, Montreal, and her associates.

Moreover, combining the results of both tests improved sensitivity only “marginally” over that achieved with HPV testing alone, “while doubling the number of tests and increasing referrals” for colposcopy.

“It is difficult to predict whether a change from Pap testing to HPV testing will further reduce the rates of death from cervical cancer.” However, “we believe that a shift from cellular to viral tests, coupled with education and vaccination, will contribute to a more efficient control of cervical cancer,” the investigators said (N. Engl. J. Med. 2007;357:1579–88).

The second study was a population-based trial in which more than 12,000 women in their mid-30s in five Swedish cities were randomly assigned to undergo Pap testing plus HPV DNA testing or Pap testing alone between 1997 and 2000. With the addition of HPV testing, 51% more cases of grade 2 or 3 cervical intraepithelial neoplasia (CIN) or cancer were detected, said Dr. Pontus Naucler of Lund (Sweden) University and associates.

The incidence of such lesions detected on subsequent screens during 4 years of follow-up decreased by a statistically significant 47%. This “represents a gain in lead time”—earlier diagnosis of high-grade lesions rather than overdiagnosis of lesions that otherwise would have regressed spontaneously, they noted (N. Engl. J. Med. 2007;357:1589–97).

This also means that HPV testing may reduce mortality from cervical cancer in women who undergo screening less often than is recommended, Dr. Naucler and associates added.

Dr. Runowicz said that if further studies confirm these findings, “there will be a need to develop a rapid, simple, accurate, and affordable HPV DNA test.” New algorithms for screening also will need to be developed.

The optimal screening approach—based on cytology, virology, or both—“will depend on the prevalence of disease, access to screening, and available resources” in any given region, Dr. Runowicz noted (N. Engl. J. Med. 2007;357:1650–3).

The CCCaST study was supported by a grant from the Canadian Institutes of Health Research and partially by an unrestricted grant from Merck Frosst Canada Ltd. The Swedish study was supported by grants from the Swedish Cancer Society and Europe Against Cancer.

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