The Role of Human Papilloma Virus Testing in Cervical Cancer Prevention

Molly C. Fey, FNP, MSN; Margaret W. Beal, CNM, PhD


J Midwifery Womens Health. 2004;49(1) 

In This Article

The 2001 Bethesda Classification Guidelines

The Bethesda system for classification and reporting of abnormal cervical cytology was developed in 1988 and revised most recently in 2001 ( Table 1 ).[14] Although it was initially designed to identify all precancerous lesions, the focus has now shifted to facilitating the detection and treatment of high-grade cervical intraepithelial lesions, based on the new understanding that most low-grade lesions, especially in young women, are associated with self-limited HPV infection.[14,15]

Despite confusion and controversy regarding equivocal Pap test results, the 2001 Bethesda guidelines have maintained the non-specific category of atypical squamous cells (ASC), mainly due to the significant number of women with moderate to severe cervical intraepithelial neoplasia (CIN II or CIN III) who are identified following such results.[14] Seventy-five percent of patients with ASC do not have cervical intraepithelial neoplasia (CIN) upon colposcopy, but there is a 10% to 20% chance that the ASC result is indicative of moderate to severe underlying CIN.[14,16] More than one third of high-grade cervical intraepithelial lesions are identified as a result of colposcopic follow-up of an equivocal Pap.[17]

ASC Pap results, indicative of mild cervical dysplasia, are the most frequent abnormal cervical cytology finding in the United States, with a mean rate of 5.2%. Approximately 10% of laboratories report ASC rates greater than or equal to 9.9%. Two million American women annually receive an equivocal, mildly atypical report and require some form of follow-up.[17,18,19,20] A new aspect of the Bethesda system is the subcategorization of ASC into two groups: "ASC of undetermined significance" (ASC-US) and "ASC cannot exclude high-grade squamous intraepithelial lesion" (ASC-H). The new ASC-H category is thought to occur in 5% to 10% of all ASC cases. Similar to ASC-US, the finding of ASC-H is equivocal and not highly reproducible, yet this category was found to have a positive predictive value for moderate to severe CIN that was intermediate between ASC-US and HSIL, warranting its creation. Both ASC-US and ASC-H are suggestive of precancerous lesions and are not an interpretation of exclusion. The category of ASCUS: Favor Reactive has been eliminated and, if found, is to be downgraded to findings negative for intraepithelial lesion or malignancy.[14]

Categorization of squamous intraepithelial lesions remains unchanged. Classification is two-tiered and divided into low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). LSIL is meant to represent mild dysplasia and CIN, which are usually indicative of transient HPV cytopathic effect. HPV cytopathic effect (koilocytosis) cannot be consistently differentiated from mild dysplasia; thus, all are included under the categorization LSIL.[14] HSIL is associated with moderate to severe dysplasia and CIN, typical of persistent HPV infection and higher risk of progression. Analysis of data from the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) supports leaving this classification unchanged.[14,21] Results of this study indicate that the division between LSIL and HSIL is reproducible, whereas a subdivision of HSIL into moderate and severe categories is not.

It is important to recognize that evaluation of cervical cytology via the Pap test is a screening tool, not one that provides a diagnosis. As emphasized by the authors of the new Bethesda Guidelines, cervical cytology provides only an interpretation that contributes to decision making and must be applied in the context of each clinical situation.[14]


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