DNA test often best for triage of cervical cancer risk

Potentially or mildly abnormal Pap results usually should be followed up with a DNA-based test rather than with another cervical smear to determine whether patients are at risk for cervical cancer, indicate the findings of a study published by Cochrane Database of Systematic Reviews, 2013 (2013;3:CD008054). However, the type of lesion being evaluated may influence which type of testing is the better choice.

As lead researcher Marc Arbyn of the Unit of Cancer Epidemiology at the Scientific Institute of Public Health in Brussels, Belgium, and colleagues noted, atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesions (LSILs) are detectable by cytological examination of cells collected from the surface of the cervix. Usually, women with these minor lesions of the cervical epithelium do not have cervical cancer or precancer, but a substantial proportion of them do have underlying high-grade cervical intraepithelial neoplasia (CIN), grade 2 or 3.

Arbyn's team sought to compare two methods of identifying women with ASCUS or LSIL who need further management: repeating the cytological test, or administering DNA testing for high-risk types of the human papillomavirus (hrHPV), the main causal factor of cervical cancer. DNA testing involved the Hybrid Capture 2 (HC2) assay, which tests for DNA from HPV strains that represent higher risk for cervical cancer.

Using data from 39 studies involving a total of 13,196 women and additional information obtained from authors of some of those studies, Arbyn and fellow researchers performed two groups of meta-analyses. Group I concerned triage of women with ASCUS, and group II concerned women with LSIL.

The investigators found that the HC2 test more accurately identified women with precancer than did repeat cervical smear. However, the specificity of HC2 was substantially and significantly lower than that of repeat cytology in the triage of LSIL.

Arbyn's group concluded that HC2 can be recommended to triage women with ASCUS because compared with repeat cytology, the DNA test is more accurate (significantly higher sensitivity and similar specificity). But when triaging women with LSIL, practitioners should be aware that the HC2 test yields significantly higher sensitivity yet significantly lower specificity than does repeat cytology.

“Therefore, practice recommendations for management of women with LSIL should be balanced, taking local circumstances into account,” advised the authors.

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