Carcinogenesis Advance Access originally published online on February 28, 2008
Carcinogenesis 2008 29(4):840-845; doi:10.1093/carcin/bgm287
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Biological behavior of CIN lesions is predictable by multiple parameter logistic regression models
1 Department of Medical Microbiology, Nijmegen University Centre for Infectious Diseases
2 Department of Obstetrics and Gynaecology
3 Department of Pathology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
* To whom correspondence should be addressed. Tel: +31 24 361 3198; Fax: +31 24 366 8597; Email: d.vanhamont{at}obgyn.umcn.nl
Objectives: Progression and regression of premalignant cervical lesions cannot be predicted using conventional cytomorphological or histomorphological parameters. However, markers such as human papillomavirus (HPV) or makers indicating proliferation, genetic instability and chromosomal aberration may be of predictive value assessing short-term biological behavior of cervical intraepithelial neoplasia. In this paper, we have studied the usage of logistic regression models with Ki-67 labeling index (LI), chromosome index for chromosome 1 (CI#1) 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 multiparameter logistic regression model containing the parameters Ki-67 LI, CI#1 and the fraction of cells with four copies of chromosome 1 per nucleus appeared to be the best predicting model, overall correct classification of 93.2% (area under the receiver operating characteristic curve 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 human papillomavirus-positive women with minimally abnormal smears applying a model as such can be useful.
Abbreviations: ASC-US, atypical squamous cells of undetermined significance; AUC, area under the receiver operating characteristic curve; BMD, borderline and mild dysplasia; CI, chromosome index; CI#1, chromosome index for chromosome 1; CIN, cervical intraepithelial neoplasia; HPV, human papillomavirus; hr-HPV, high-risk human papillomavirus; HSIL-MD, high-grade squamous intraepithelial lesion of the moderate dysplasia type; LI, labeling index; LLETZ, large-loop excision of the transformation zone of the cervix; LSIL, low-grade squamous intraepithelial lesion; PBS, phosphate-buffered saline; PC, polymerase chain reaction; SSC, standard saline citrate
Received May 3, 2007; revised December 6, 2007; accepted December 8, 2007.