Human Papillomavirus Triage of Atypical Squamous Cells of Undetermined Significance: Cost-Effective, But At What Cost?

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Since the introduction of cytology for cervical cancer screening more than 50 years ago, deaths from cervical cancer in the United States have declined by about 75% ( 1 ) . However, an estimated 3700 women will die from cervical cancer in the United States in 2005 ( 2 ) . Among the 55 million Pap smears performed in the United States annually, roughly 3 million show atypical cells of undetermined significance (ASCUS), a conundrum for pathologists, clinicians, and patients ( 3 ) .

Great strides have been made in understanding the underlying biology of cervical cancer. Infection with an oncogenic human papillomavirus (HPV) is necessary but not sufficient for its development. Recent research has attempted to improve the sensitivity of cervical cancer screening to reduce false-negative tests and hence prevent more deaths from cervical cancer. Testing for oncogenic HPV has been shown in the ALTS trial ( 3 ) and other studies ( 4 – 6 ) to be an effective triage strategy for women with ASCUS, identifying a great majority of women with underlying cervical intraepithelial neoplasia. In this strategy, women with ASCUS who test positive for oncogenic HPV are referred for colposcopy, whereas those with negative test results return to routine screening.