Superficial nuclear enlargement without koilocytosis as an expression of human papillomavirus infection of the uterine cervix : an in situ hybridization study

: Nuclear enlargement of the superficial cervical epithelial cells in the absence of koilocytosis is frequently observed. The purpose of this study was to investigate whether this change represents human papillomavirus (HPV) infection. We reviewed 257 cervical biopsies with the diagnosis of "suggestive of condyloma," mild or moderate dysplasia, or both. Of the 257 consecutive biopsies, 23 fulfilled the two criteria: the superficial cells had a nuclear diameter of at least twice that of the basal nuclei, and complete absence of koilocytosis was seen. Parallel sections from each paraffin block were hybridized with biotinylated probes for HPV 6/11, 16/18, and 31/35/51 under high-stringency conditions. The cases that were negative at high-stringency conditions were then hybridized under low-stringency conditions with a mixture of the three HPV probes. Twelve of the 23 cases (52.17%) were positive for HPV, including one positive for HPV 16/18 in one area and for HPV 31/35/51 in another area, four positive for HPV 31/35/51, two positive for HPV 16/18, two positive for HPV 6/11, and three positive for HPV probe mixture at low-stringency conditions. The positive in situ hybridization was located predominantly in the enlarged nuclei in the superficial layers. In conclusion, HPV infection can be expressed as nuclear enlargement in the superficial layers of the cervical epithelium in the absence of koilocytosis.