In 2003, the FDA approved HPV DNA testing combined with cervical cytology as a screening technique for women older than age 30. When the results of both tests are negative, the woman does not have to be retested for 3 years. The negative predictive value of a double negative test exceeds 99% (19). Because most HPV infections are transient, clear spontaneously, and do not lead to real cancer precursors (especially in young women), it should not be used for screening in women younger than 30 (63). Women who have negative test results for both cytology and HPV have a 1 in 1,000 chance of having CIN 2 or worse detected in the following 6 months (64). Prospective studies report less than 2 per 1,000 women will develop CIN 2 or greater in the following 3 years (64–66).
Atypical Squamous Cells The ASC category is restricted to those test results disclosing abnormal cells that are truly of unknown significance. The ASC category does not include benign, reactive, and reparative changes, which are classified as normal in the Bethesda system. Because of the subjective diagnostic criteria and the fear of medical–legal action, the diagnosis is relatively common, ranging from 3% to 25% in some centers (67). When standardized diagnostic criteria are used, the rate of ASC results should be 3% to 5% (68). The ASC category is subdivided into ASC-US and ASC-H.
The cytologic diagnosis of ASC-US is associated with a 10% to 20% incidence of CIN 1 and a 3% to 5% risk forCIN 2 or 3 (69–72). It is apparent that CIN 1 is most often a benign HPV infection and will regress spontaneously in more than 60% of cases; therefore, the goal of triage of an ASC-US Pap test result is to identify more advanced CIN 2 and 3 lesions (73).
The option of repeat Pap testing is suboptimal because of a false-negative rate of 20% to 50% for identifying CIN lesions and practical issues with patient compliance. About 50% of patients will undergo colposcopy because of subsequent abnormal Pap test results, making this option nearly as costly as immediate colposcopy (69). Immediate colposcopy is assumed to be the most sensitive method of detecting CIN 2 or 3 (69,72). Because 80% of patients will not have significant lesions, it is important to avoid overinterpretation of the colposcopic findings and to be conservative in performing biopsies. There is the risk that pathologists will overinterpret the biopsy results and the patient will be diagnosed with CIN when metaplasia is the only finding.