Women who have an indeterminate Pap smear should undergo human papillomavirus (HPV) testing rather than another Pap smear, according to the results of Cochrane Review.

Cancer screening refers to the use of tests to detect cancer in individuals who do not have any symptoms of the disease. In general, the primary goal of screening is to reduce cancer deaths by detecting cancer at an earlier and more treatable stage. For some types of cancer—including cervical cancer—screening can also play a role in cancer prevention. Screening for cervical cancer can identify precancerous changes to the cervix. Treatment of these precancers can then prevent the development of invasive cancer.

The Pap test is a screening test that has had a tremendous impact on cervical cancer incidence and mortality. During a Pap test, a sample of cells is removed from the cervix and evaluated under a microscope. The results of the Pap test are generally classified into one of several categories ranging from normal to cancerous. Two of these categories—atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intra-epithelial lesions (LSIL)—are considered indeterminate and may require further testing.

More recently, tests for high-risk types of human papillomavirus (HPV) have also been incorporated into cervical cancer screening programs. Persistent HPV infection causes most cases of cervical cancer. Researchers continue to evaluate the best way to triage women with ASCUS or LSIL—a repeated Pap test or an HPV test.

Researchers compared the accuracy of HPV testing with the Hybrid Capture 2 (HC2) assay against that of repeat Pap test for detection of underlying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) or grade 3 or worse (CIN3+) in women with ASCUS or LSIL. They performed a comprehensive review of 39 studies that included women with ASCUS or LSIL who had undergone HPV testing and repeat Pap test or HPV testing alone, with verification by colposcopy and colposcopy-directed biopsies. There were two groups of meta-analyses: 13,196 women with ASCUS and 9,983 women with LSIL.

The results indicated that the HPV test had 27% better sensitivity and equal specificity in detecting high-grade cervical precancers in women with an initial finding of ASCUS. In women with LSIL, the HPV test also missed fewer high-grade lesions, with 23% better sensitivity than repeat Pap test.

The researchers concluded that the HPV test can be recommended for triaging women with ASCUS because it has a higher accuracy than repeat Pap test. However, when triaging women with LSIL, an HPV test yields a significantly higher sensitivity, but significantly lower specificity than a repeat Pap test. Therefore, they recommend that the management of LSIL should be balanced and take individual circumstances into account.


Arbyn M, Roelens J, Simoens C, et al. Human papillomavirus testing versus repeat cytology for triage of minor cytological cervical lesions. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD008054. DOI: 10.1002/14651858.CD008054.pub2

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