The role of deeper levels and ancillary studies (p16Ink4a and ProExC) in reducing the discordance rate of Papanicolaou findings of high-grade squamous intraepithelial lesion and follow-up cervical biopsies

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Discordant results of cervical biopsy histology after a cytologic diagnosis of high-grade squamous intraepithelial lesion (HSIL) are often attributed to sampling variation. The purpose of the current study was to determine whether deeper levels and ancillary staining (p16Ink4a and ProExC) reduce the discordant rate.


A total of 246 cases of HSIL were retrieved from the computerized database from 2005 and 2006. Of these cases, 151 were followed by cervical biopsy. There was cytologic-histologic correlation in 87 cases, as defined by the presence of high-grade (2 or 3) cervical intraepithelial neoplasia (HGCIN). For each discordant biopsy (n = 64), 2 deeper levels for hematoxylin and eosin (H&E) were taken at 30-μ and 90-μ depths, and 4 sections for p16Ink4a and ProExC staining were taken at a 60-μ depth. All cytologic and histologic material from these 64 cases was reviewed by 3 cytopathologists. In 2 cases, the original HSIL diagnoses were downgraded and the cases censored from the study.


Fifty-seven of the 62 discordant cases had sufficient tissue for deeper levels and ancillary staining. Two of 57 cases were reclassified to HGCIN. In both of these cases, reclassification was suggested by results of immunostains; however, the H&E sections were necessary for definitive interpretation of the immunostain results.


In the current study, deeper levels and ancillary staining with p16Ink4a and ProExC did not significantly reduce the discordance rate. Although there are many known causes of sampling variation, including factors related to colposcopic technique, regression of infection, and insufficient histologic sectioning, sampling variation remains a valid justification of noncorrelation in women with HSIL followed up by cervical biopsy alone.

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