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Clin Lab Med. 2003 Sep;23(3):605-32.

Atypical squamous cells: update on current concepts.

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  • 1Department of Pathology, Northwestern University, Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, IL 60611, USA.


Besides all the confusion and associated problems that the use of ASC has created, it has initiated substantial investigational interest that has resulted in a better understanding of squamous intraepithelial lesions and the biology of cervical neoplasia. Although the category of ASC has created, and will continue to create, controversy in the diagnostic and management fields, it allows the pathologist to convey uncertainty that may be the result of poor sampling or difficulty in interpretation of a case. It is a valuable tool that the cytopathologist can use to make it known that the Papanicolaou test has its limitations and may need and benefit, in some instances, from support from ancillary studies. Similar limitations are recognized in other areas of pathology and the use of immunohistochemistry or molecular studies is widely accepted as an aid to a more specific and definitive interpretation. The time for the Papanicolaou test to be considered similarly has arrived. HPV DNA testing may not be the perfect test for cervical cancer screening because of high prevalence of HPV infection in the general population; however, it is currently the best-studied ancillary test and has been proven to be cost-effective for the triage of Papanicolaou tests with equivocal squamous cells. It is important for the cytopathologist to have well-developed diagnostic skills in interpreting gynecologic preparations, and to classify cases as ASC only when deemed appropriate. Downgrading cytologic findings that are diagnostic of a squamous intraepithelial lesion to ASC with the hope of supporting it by an HPV test will only result in a devaluation of the Papanicolaou test. Such recourse may, however, be acceptable in specific situations, such as in patients who have complex histories, atypical clinical presentations, or during pregnancy. Quality assurance measures to closely monitor the ASC:SIL ratio and the rate of HPV positivity in ASC cases will be essential to ensure the appropriate use of this interpretive category. The coordination of the 2001 Bethesda and ASCCP consensus meetings resulted in the new subcategories of ASC-US and ASC-H, along with well-defined management strategies for these interpretations. This new and clinically relevant terminology should lead to a reduction in difficulties at the clinical level and a more uniform management of patients, unlike the situation following Bethesda 1991 where the gynecologist was faced with a new "diagnosis" without specific management recommendations. The standardization of reporting and clinical management will also allow more reliable evaluation of patient outcomes and cost analysis. The 2002 American Cancer Society guidelines did not make specific recommendations regarding HPV DNA testing for the triage of patients who have a cytology result of ASC-US [64]. The FDA approved the expanded use of HPV testing in conjunction with the Papanicolaou test for cervical cancer screening in March of 2003. The future is likely to bring additional testing modalities that may be more specific for detecting squamous lesions that are more likely to persist or progress to carcinoma, than the currently available HPV tests. In addition, looking to the more distant future, recently published data from HPV vaccine trials suggests that immunizing women who are negative for HPV-16 may eventually reduce the incidence of cervical cancer [65]. At the present, however, the most effective method to decrease the mortality of this disease process is to make sure that all women have access to, and receive, effective cervical cytologic screening.

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