Prognostic value and reproducibility of koilocytosis in cervical intraepithelial neoplasia

The purpose of this study was to evaluate the influence of koilocytosis on the progression of cervical intraepithelial neoplasia (CIN) to a higher grade during follow-up in cervical biopsy specimens with CIN 1 and 2. In adequate, consecutive, biopsy specimens of 103 CIN 1 and 2 patients, CIN grade and presence or absence of koilocytosis were assessed. Patients were followed by colposcopy and cytology according to protocol. When recurrent CIN was suspected with either of the techniques, a re-biopsy was taken. Progression of the CIN was defined as an increase of grade by at least 1. Univariate analysis was applied to all patients and in the CIN 1 and 2 subgroups separately. An experienced gynecological pathologist using strict criteria reviewed koilocytosis. The Kappa test was used to assess interobserver reproducibility of koilocytosis. Koilocytosis was found in 70 (68%) of the specimens (18 of 29=62% of the CIN 1 and 52 of 74=70% of the CIN 2 cases). Twenty-one of 103 (20%) dysplasias progressed and 10 of these (48%) showed koilocytosis. Koilocytosis was found more frequently (73%, 60 of 82) in the cases that showed no progression. Follow-up showed that patients with koilocytosis had a significantly lower likelihood of progression (log-rank=5.5, p=0.02). In CIN 1, progression without and with koilocytosis was 27% and 0%, respectively, log-rank=4.9, p=0.03. In CIN 2, a similar trend was found: only 10 of 52 (19%) CIN 2 cases with koilocytosis progressed, whereas 8 of 22 (36%) lesions lacking koilocytosis progressed, a difference just below significance (p=0.06). In agreement with other studies, interobserver diagnosis of koilocytosis was poorly reproducible. In conclusion, the presence of koilocytosis is associated with a lack of progression in CIN 1 lesions, but reproducibility of koilocytosis assessment is not optimal. Therefore, other more objective and better reproducible criteria are required to extract the potentially important prognostic information contained in the microscopic image of CIN 1 and 2 lesions.