Increased incidence of atypical Papanicolaou tests from ThinPreps of postmenopausal women receiving hormone replacement therapy

BACKGROUND The authors noticed a significant increase in the rate of atypical squamous cells of undetermined significance (ASCUS) diagnoses in postmenopausal women receiving hormone replacement therapy with ThinPrep (monolayer) Papanicolaou (Pap) tests (8.3%) as compared with conventional Pap tests (2.3%; P = 0.025). The purpose of this study was to correlate these morphologic changes with human papillomavirus (HPV) DNA detection by in situ hybridization and clinical outcome. METHODS Twenty‐five monolayer Pap tests diagnosed as ASCUS in postmenopausal women receiving hormone replacement, as well as 2 cases of low‐grade squamous intraepithelial lesion (SIL) from the same group, were destained in acid alcohol. In situ HPV hybridization was performed with a consensus probe that can detect greater than 90% of the HPV types that occur in cervical SIL. In addition, 11 of the ASCUS tests were analyzed with the periodic acid–Schiff (PAS) stain. RESULTS All 25 ASCUS tests were negative for HPV DNA as compared with a detection rate of 15 of 17(88%) for low‐grade SIL. Glycogen that was PAS positive was present in the atypical squamous cells of the postmenopausal women for whom HPV was not detected. Clinical follow‐up demonstrated that only 2 of the 25 women with ASCUS had a subsequent biopsy proven SIL. CONCLUSIONS The ThinPrep preparation can produce artifactual HPV‐like changes in postmenopausal women receiving hormone replacement therapy that may be caused by glycogenization and, because of the high incidence of HPV negativity and negative clinical outcome, are best considered as benign cellular changes. Cancer (Cancer Cytopathol) 2001;93:357–63. © 2001 American Cancer Society. The ThinPrep preparation produces artifactual human papillomavirus (HPV)–like changes in postmenopausal women receiving hormone replacement therapy. These changes may be caused by glycogenization and, because of the high incidence of HPV negativity and negative clinical outcome, are best considered as benign cellular changes.