DNA ploidy compared with human papilloma virus testing (Hybrid Capture II) and conventional cervical cytology as a primary screening test for cervical high‐grade lesions and cancer in 1555 patients with biopsy confirmation

Abstract

BACKGROUND.Because 80% of cervical cancers arise in low‐resource settings, many inexpensive strategies are being tested. In that spirit, the authors are testing large‐scale genomic or DNA ploidy measurements as an inexpensive and semiautomated strategy.METHODS.Patients entered either a screening or diagnostic study of several optical technologies: quantitative cytology, quantitative histopathology, and fluorescence and reflectance spectroscopy using a point probe, a multispectral digital colposcope, or a combination of the two. We calculated sensitivities, specificities, positive and negative predictive values, and their confidence interval testing conventional cytology, Hybrid Capture (HC) II testing, and DNA ploidy measured on the Feulgen‐stained quantitative Pap smear.RESULTS.The current investigation reports on 1555 patients for whom colposcopically directed biopsies were read 3 times by study pathologists. The final histopathologic diagnosis was high grade (cervical intraepithelial neoplasia [CIN] 2, CIN 3, carcinoma in situ [CIS], and cancer) in 16% of patients. Using high‐grade squamous intraepithelial lesions (SILs) histopathology as the threshold and gold standard, the sensitivity and specificity, respectively, were: 0.47 and 0.96 for conventional cytology, 0.91 and 0.80 for HC II, and 0.59 and 0.93 for DNA ploidy. The positive and negative predictive values (PPV, NPV) for conventional cytology were 0.70 and 0.90, 0.46 and 0.98 for HC II, and 0.63 and 0.92 for DNA ploidy.CONCLUSIONS.DNA ploidy shows comparable sensitivity, specificity, PPV, and NPV values to conventional cytology and HC II. Unlike conventional cytology, DNA ploidy is semiautomated and can be performed in less than 8 hours. Cost effectiveness studies are under way, but in the authors' laboratory DNA ploidy is inexpensive. Cancer 2006. © 2006 American Cancer Society.

Automated Quantification of DNA Aneuploidy by Image Cytometry as an Adjunct for the Cytologic Diagnosis of Malignant Effusion

“…In our study, we found that the cut off value of 5c for aneuploidy determined by automated DNA ICM used for cervical and esophageal cancer detection [5,6,16] and 4.6c use for oral cancer detection should not be used as threshold values for effusion cytology diagnosis, as it is not as robotic as the 2.5c we identified. This is due to the fact that malignant cells in cervical, esophageal and oral cancer are squamous cell carcinoma while malignant cells in effusion are largely adenocarcinoma.…”

“…The system consisted of a computer controlled motorized microscope and high-resolution digital camera for image scanning and capturing, and software for controlling of image scanning, processing and analysis. The software used for the automatic classification of cells, measurement of DNA ploidy and analysis of aneuploidy was derived from the British Columbia Cancer Agency, Vancouver, Canada [16]. For each slide, 1000 cell nuclei or all of the cell nuclei on the slide were scanned and nuclear images were collected into a nuclear DNA image gallery.…”

“…Previous studies have reported cut off values of 3 cells with DNA ploidy index above 5c for cervical and esophageal cancer detection [5,16], 3 cells with DNA ploidy index above 4.6c for oral cancer detection [7] as well as 1 cell exceeding 9c for tumor detection by DNA ploidy [19]. Sensitivity, specificity, PPV and NPV of DNA aneuploidy for diagnosis of effusion were also calculated using the previously described criteria of DNA image cytometry and compared with the optimal threshold values we identified in this study.…”

Automated Quantitative Cytology Imaging Analysis System in Cervical Cancer Screening in Shanxi Province, China

“…One of criteria is measurement of nuclear DNA content together with set of features for cell morphology recognition such as nuclear to cytoplasm ratio. This method was described and used previously (Guillaud et al, 2006) All scanned slides were first reviewed by trained technician who had 2-5 years of experience. Cervical cytology reports were classified according to Bethesda (TBS) diagnostic system and were reported as: ASCUS, ASC-H, LSIL, HSIL, cancer and other positive.…”

Established and Emerging Optical Technologies for the Real-Time Detection of Cervical Neoplasia: A Review

“…These three changes form the basis for the biological basis for the adoption on new technologies. Table 1 shows endoscope-compatible optical technologies and their role in cancer screening and detection in all organ sites [19]. We know that as intraepithelial neoplasia develops, it secretes growth factors that increase the vasculature to supply nutrients to the lesion.…”