Carcinogenesis Advance Access first published online on February 28, 2008
This version published online on March 6, 2008
Carcinogenesis, doi:10.1093/carcin/bgm287
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Biological behavior of CIN lesions is predictable by multiple parameter logistic regression models
Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
1 Department of Medical Microbiology, Nijmegen University Centre for Infectious Diseases
2 Department of Obstetrics and Gynaecology
3 Department of Pathology
4 to whom correspondence should be addressed at: Radboud University Nijmegen Medical Centre, Department of Obstetrics and Gynaecology (intern mail 791), P.O. box 9101, 6500 HB Nijmegen, The Netherlands, E-mail address: d.vanhamont{at}obgyn.umcn.nl, Telephone number: +31-(0)24-3613198, Fax number: +31-(0)24-3668597
Objectives: Progression and regression of pre-malignant cervical lesions cannot be predicted using conventional cytomorphological or histomorphological parameters. However, markers such as HPV or makers indicating proliferation, genetic instability and chromosomal aberration may be of predictive value assessing short-term biological behavior of cervical intraepithelial neoplasia (CIN). In this paper we have studied the usage of logistic regression models with Ki-67 labeling index (LI), chromosome index (CI) and aneusomy for chromosome 1 in cervical smears to predict progressive and regressive behavior of premalignant cervical lesions.
Methods: Retrospectively, the intake-smears of 42 women showing regression in follow-up and of 31 women showing progression in follow-up were assessed.
Results: A multi-parameter logistic regression model containing the parameters Ki-67 LI, CI#1, and the fraction of cells with 4 copies of chromosome 1 per nucleus appeared to be the best predicting model, overall correct classification of 93.2% (AUC 0.96±0.02). After cross-validation, the model correctly classified 66 of 73 samples (90.4%). Moreover, the model predicted biological behavior perfectly assessing the smear taken subsequently to the intake-smear of 46 women.
Conclusion: Although measuring parameters indicating proliferation and chromosome 1 aberration is laborious, this study demonstrates that short-term progressive and regressive behavior is highly predictable using a model combing these parameters. We also showed that in the triage management of high-risk HPV positive women with minimally abnormal smears applying a model as such can be useful.
Key Words: Cervical intraepithelial neoplasia • progression • regression • predictive value • Ki-67 • MIB1 • chromosome index
Received May 3, 2007; revised December 6, 2007; accepted December 8, 2007.