Almost all cases of cervical cancer are caused by infection with HPV. Cervical abnormalities that are found during routine Pap smears are quite common, and many of these abnormalities disappear without ever causing problems. The most definitive way to determine if an abnormality has the potential to become cancerous is to perform a biopsy obtained by colposcopy, which is more invasive than a Pap smear. Because it would be expensive and stressful for patients to undergo invasive testing for all cervical abnormalities, it is important to look for factors that distinguish precancerous abnormalities from benign ones.
Several clinical trials have examined different triage methods for various types of cervical abnormalities. One management strategy for one of the most common abnormalities, atypical squamous cells of undetermined significance (ASCUS), is to perform another Pap smear 6 to 12 months later to see if ASCUS is still present. If so, the woman would then have a colposcopy to see if there is abnormal cell growth on the surface of the cervix that has the potential to become cancerous, a condition referred to as high-grade cervical intraepithelial neoplasia (CIN2). Another management strategy under investigation is to test for HPV in women with a diagnosis of ASCUS.
Marc Arbyn, M.D., of the Scientific Institute of Public Health in Brussels, Belgium, and colleagues gathered data from 15 studies of management strategies of ASCUS. They found that HPV testing accurately identified 84.4% of women who had CIN2 or worse (a measure of a test's sensitivity), and it accurately ruled out CIN2 or worse (a measure of a test's specificity) in 72.9% of women with ASCUS. When the investigators looked only at studies that used a recently developed test for HPV, called the Hybrid Capture II assay, they found that HPV testing had a sensitivity of 94.8% and a specificity of 67.3%. In contrast, a repeat Pap smear accurately identified 81.8% of women with CIN2 or worse and accurately ruled out clinically significant disease in 57.6% of women.
"[T]he results ... are helpful in solidifying our understanding of HPV DNA testing and repeat cytology in the triage of equivocal Pap tests, and in directing the course of future research," write editorialists Diane Solomon, M.D., and Mark Schiffman, M.D., of the National Cancer Institute, who are both investigators on a large, randomized clinical trial called ALTS that is examining management strategies for women with cervical abnormalities. They point out some weaknesses in the meta-analysis and note that some of these stem from the fact that cervical cancer screening is a rapidly evolving field. "Eventually, we hope to identify and validate markers of cancer risk that are even more accurate than either cytology or HPV DNA testing," they write.
Contacts:
- Article: Dr. Marc Arbyn, Scientific Institute of Public Health, (32) 2 642 50 21, marc.arbyn@iph.fgov.be
- Editorial: NCI Press Office, 301-496-6641, ncipressofficers@mail.nih.gov
Citations:
- Arbyn M, Buntinx F, Van Ranst M, Paraskevaidis E, Martin-Hirsh P, Dillner J. Virologic versus cytologic triage of women with equivocal Pap smears: a meta-analysis of the accuracy to detect high-grade intraepithelial neoplasia. J Natl Cancer Inst 2004;96:280-93.
- Editorial: Solomon D, Schiffman M. Have We Resolved How To Triage Equivocal Cervical Cytology? J Natl Cancer Inst 2004;96:250-1.
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JNCI Journal of the National Cancer Institute