Improved Detection of Cervical Cancer and High Grade Neoplastic Lesions by a Combination of Conventional Cytology and DNA Automated Image Cytometer

Zuming Li, Min Zhang, Hua Li

Yiling Women and Children Hospital, Yichang, China.
Zhongshan Hospital, Wuhan, China.
Zhongshan Hospital, Wuhan, China..

DOI: 10.4236/jct.2010.12008                

Abstract

OBJECTIVE: To reduce false-negative rates of population based cervical screening programs employing conventional cytology in combination with automated DNA image cytometer. METHODS: Involved cervical samples from a total of 3603 women were taken by a cervix brush and then placed into a fixative solution. The cells were separated from mucus by mechanical and chemical treatment after which they were deposited onto microscope slides by a cytospin. Two slides were prepared from each case; one slide was stained by Papanicolaou stain for conventional cytology examination, while the other slide was stained by a DNA specific and stoichiometric stain. The latter slide was used to determine the relative amount of DNA in the cell nuclei in order to assess the ploidy status of the epithelial cells. Enrolled in the study, 157 women were followed by colposcopy examination where punch biopsies were taken from the visible lesions or from suspicious areas. The results of the conventional cytology were then compared to the DNA image cytometer for all samples. RESULTS: Histopathology diagnosed 51 lesions from the 132 biopsied cases as CIN2 or higher, including 27 CIN2, 16 CIN3 and 8 invasive cancers. Conventional cytology correctly identified 29 of the 51 high grade CIN and in-vasive cancer, while DNA image cytometer correctly identified 38 high grade CIN and invasive cancer using the crite-rion that at least three cells were found on the slide that contained DNA amount in excess of 5c. 42 out of 51 high grade CIN and invasive cancer were found by conventional cytology in combination with DNA image cytometer. Sensitivities were 56.8%, 74.5% and 82.4%, while specificities were 86.2%, 81.5% and 81.5% in conventional cytology, DNA image cytometer and combination both cytology and DNA image cytometer respectively. CONCLUSION: The study demon-strated that screening for high grade neoplastic lesions and cervical cancer by DNA image cytometer or combination of conventional cytology and DNA image cytometer is more sensitive than conventional screening approach.

Keywords

Cervical Intraepithelial Neoplasia (CIN), Conventional Cytology, Image Cytometry, Ploidy, Aneuploid Cells, Invasive Cervical Cancer

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	S. Liu, R. Semenciw, A. Probert and Y. Mao, “Cervical Cancer in Canada: Changing Patterns in Incidence and Mortality,” International Journal of Gynecological Cancer, Vol. 11, 2001, pp. 24-31.
[2]	G. H. Anderson, D. A. Boyes, J. L. Benedet, J. C. LeRiche, J. P. Matisic, K. C. Suen, A. J. Worth, A. Millner and O. M. Bennett, “Organisation and Results of the Cervical Cytology Screening Programme in British Columbia, 1955-1985,” Britain Medical Journal, Vol. 296, 1988, pp. 975-978.
[3]	F. Guidozzi, “Screening for Cervical Cancer,” Obstetrical & Gynecological Survey, Vol. 51, 1996, pp. 247-252.
[4]	J. D. Gay, L. D. Donaldson and J. R. Goellner, “False-negative Results in Cervical Cytologic Studies,” Acta Cytologica, Vol. 29, 1985, pp. 1043-1046.
[5]	M. R. Kok, M. E. Boon, P. G. Schreiner-Kok, L. G. Koss, “Cytological Recognition of Invasive Squamous Cancer of the Uterine Cervix: Comparison of Conventional Light-Micro-Scopical Screening and Neural Network- Based Screening,” Human Pathology, Vol. 31, 2000, pp. 23-28.
[6]	S. E. Barton, D. Jenkins, A. Hollingworth, J. Cuzick and A. Singer, “An Explanation for the Problem of False- Negative Cervical Smears,” British Journal of Obstet Gynaecol, Vol. 96, 1989, pp. 482-485.
[7]	Y. van der Graaf, G. P. Vooijs, H. L. J. Gaillard and D. M. Go, “Screening Errors in Cervical Cytologic Screening,” Acta Cytologica, Vol. 31, 1987, pp. 434-438.
[8]	D. M. Garner, A. Harrison and C. F. MacAulay, “CytoSavantTM and its Use in Automated Screening of Cervical Smears. Compendium on the Computerized Cytology and Histology Laboratory,” In: G. L. Wied Ed., Tutorial of Cytology, Chicago, 1994, pp. 346-352.
[9]	M. Bibbo, P. H. Bartels, H. E. Dytch and G. L. Wied, “Cell Image Analysis. Comprehensive Cytopatholgy,” In: M. I. Bibbo Ed., W. B. Saunders Company, Philadelphia, 1991, pp. 965-983.
[10]	A. Bocking and V. Q. Nguyen, “Diagnostic and Prognos-tic Use of DNA Image Cytometry in Cervical Squamous Intraepithelial Lesions and Invasive Carcinoma,” Cancer, Vol. 102, 2004, pp. 41-54.
[11]	A. Mayer, M. Hockel, O. Thews, K. Schlenger and P. Vaupel, “Impact of Oxygenation Status and Patient Age on DNA Content in Cancers of the Uterine Cervix,” In-ternational Journal of Radiation Oncology Biology Physics, Vol. 56, 2003, pp. 929-936.
[12]	X. R. Sun, J. Wang and L. Li, “Methods of DNA Quanti-tative Cytology. DNA Quantitative Cytology,” In: X. R. Sun and J. Wang Eds., Hubei Science and Technology press, Wuhan, 2006, pp. 22-26.
[13]	G. Auer, T. O. Caspersson and A. S. Wallgren, “DNA Content and Survical in Mammary Carcinoma,” Analytical & Quantitative Cytology, Vol. 2, 1980, pp. 161-165.
[14]	M. Guillaud, L. B. John, B. C. Scott, et al., “DNA Ploidy Compared with Human Papilloma Virus Testing (Hybrid Capture II) and Conventional Cervical Cytology as a Pri-mary Screening Test for Cervical High-Grade Lesions and Cancer in 1555 Patients with Biopsy Confirmation,” Cancer, Vol. 107, 2006, pp. 309-318.
[15]	H. Tong, R. Shen, Z. M. Wang, et al., “DNA Ploidy Cy-tometry Testing for Cervical Cancer Screening in China (DNA CIC Trial): A Prospective Randomized, Controlled Trial,” Clinical Cancer Research, Vol. 15, 2009, pp. 6438-6445.
[16]	A. Bocking and V. Q. H. Nguyen, “Diagnostic and Prognostic Use of DNA Image Cytometry in Cervical Squamous Intraepithelial Lesions and Invasive Carcinoma,” Cancer Cytopathology, Vol. 102, 2004, pp. 41-54.