• Papanicolaou test;
  • high-grade squamous intraepithelial lesion;
  • cervical biopsy;
  • sampling error



Sampling error is a common explanation of noncorrelation in women whose Papanicolaou (Pap) tests show high-grade intraepithelial lesions (HSIL) but whose follow-up cervical biopsies show only cervical intraepithelial neoplasia (CIN) 1, koilocytosis, or reactive/inflammatory changes. The purpose of this study was to demonstrate the validity of sampling error in this setting by determining the proportion of negative colposcopic cervical biopsies in women with HSIL who subsequently undergo cone/loop electrode excision procedure (LEEP) biopsies or repeat cervical biopsies that confirm the diagnosis of high-grade CIN (HGCIN).


In all, 368 cases of HSIL were retrieved from the computerized database from January 1, 2003 to December 31, 2005. Follow-up was obtained as part of routine quality assurance/quality control activities including cytologic-histologic correlation.


A total of 368 HSIL Pap diagnoses were retrieved. Of the 254 cases that were followed up by cervical biopsy, 146 showed HGCIN in the biopsy. Of the remaining 108 patients whose cervical biopsies failed to demonstrate HGCIN, 47 had a subsequent procedure, either cone/LEEP, cervical biopsy, or repeat Pap test. Cone biopsy/LEEP was performed in 34 cases (72.3%) with a diagnosis of HGCIN in 19. Repeat cervical biopsy was performed in 9 cases (19.1%) with HGCIN diagnosed in 5. Repeat Pap test was performed in 4 cases (8.5%) with HSIL diagnosed in 2.


In the population of women with HSIL by Pap test followed up by cervical biopsy with or without subsequent cone/LEEP, there was a discordant cervical biopsy rate for HGCIN of 43%. In the subgroup of women with HSIL by Pap test followed up by cervical biopsy and subsequent cone/LEEP or repeat cervical biopsy, the proportion of women with negative colposcopic cervical biopsy and subsequent histology-proven HGCIN was 56%. These figures justify sampling error as a valid cause of noncorrelation in women with HSIL followed up by cervical biopsy alone. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.