Negative loop electrosurgical excision procedure (LEEP) following cervical biopsy diagnosis of high grade squamous intraepithelial lesion

Context: Loop Electrosurgical Excision Procedure (LEEP) is commonly performed after cervical biopsy diagnosis of high grade squamous intraepithelial lesion (HSIL/CIN2 or CIN 3). Histological and immunohistochemical assessments are made to differentiate reactive and metaplastic changes from dysplastic changes. A Human Papillomavirus (HPV) test is used for prognostic assessment after conization. Objective: We retrospectively reviewed cases where the cervical biopsy showed HSIL but the LEEP specimen was negative for high grade dysplasia. Our aim was to determine the cause of miscorrelation. Data: IRB approval was obtained and a search was made of all LEEP specimens received during 2018. We reviewed 25 of 137 LEEP specimens that did not correlate with the diagnosis of HSIL rendered on the cervical biopsy. These were from women between 25 to 54 years. All cases had positive high risk HPV with 80% being non16/18 subtype. On review, 8/25 had HSIL with the remainder of cases falling short of HSIL diagnosis. Follow up cytology with HPV test after the LEEP procedure was negative in all but one case of LSIL with persistent non-16/18 HPV. Conclusion: The study highlights the diagnostic difficulties of distinguishing HSIL from immature squamous metaplasia. The practical implication is that in cases with non-16/18 high risk HPV which have thin epithelium and fall short of definite morphologic criteria of HSIL, presence of immature squamous metaplasia should be carefully evaluated. The specific role of CK7 and CK17 which highlight squamocolumnar junctional cells and metaplastic cells, respectively, needs to be explored in these cases.