Intense research into cervical cancer detection and treatment has yielded significant progress in the past decade. One common cause of such cancer is the human papillomavirus (HPV). New developments involving HPV have produced thin-layer Pap smears, HPV testing, and HPV vaccines. Now, researchers in Italy are reporting a new twist in HPV screening and detection. In research published in the journal Lancet Oncology, Guglielmo Ronco, a cancer epidemiologist at the Centre for Cancer Prevention in Turin, reported that a new way to test for cervical cancer is more accurate than a pap smear alone and identified more dangerous lesions.

Clinicians can improve the specificity of DNA tests for HPV by testing for the presence of a protein that is over-expressed in cervical cancer cells, the new research shows. The molecular test tends to give more false positives, increasing the number of unneeded referrals for colposcopy, Ronco and colleagues reported online in the journal Lancet Oncology. (Carozzi F, et al “Use of p16-INK4A overexpression to increase the specificity of human papillomavirus testing: a nested substudy of the NTCC randomised controlled trial” Lancet Oncology 2008; DOI: 10.1016/S1470-2045(08)70208-0.)

DNA tests for HPV are more likely to pick up cases of high-grade cervical intraepithelial neoplasia (CIN) than conventional cytology, Ronco and colleagues reported. Since the molecular method gives more false positives, it tends to increase the number of unneeded referrals for colposcopy, Dr. Ronco and colleagues reported. To improve specificity, the researchers considered the cyclin-dependent kinase inhibitor p16-INK4A (p16), which is considered to be a marker of HPV infection, according to a report on the findings at

Since only a small percentage of women who have an HPV infection actually develop cancer, the challenge for researchers is to identify those who have the highest risk for developing the disease. By testing for a the presence of P16, the researchers said they had identified a biomarker showing cell changes that indicated whether a woman was likely to have pre-cancerous lesions, Ronco and colleagues reported. “The marker shows there was some sort of disruption by the HPV virus,” Ronco said.

“Our data show that in HPV-positive women, p16-INK4A over-expression is strongly associated with the presence of histologically confirmed CIN2+, suggesting that it actually is a marker of progression,” Dr. Ronco said. “This study supports the application of triage by P16INK4A immunostaining in HPV-positive women,” he added.

Data from the U.S. National Cancer Institute show that an estimated 11,000 women in the United States would be diagnosed with this type of cancer and nearly 4,000 would die from it last year. Cervical cancer strikes nearly half a million women each year worldwide, claiming a quarter of a million lives. Studies show 26% of women aged 14 to 59 will contract HPV.

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