Correlation of DNA Ploidy with Progression of Cervical Cancer

Abstract

The majority of squamous cell carcinomas of cervix are preceded by visible changes in the cervix, most often detected by cervical smear. As cervical cancer is preceded by long precancerous stages, identification of the high-risk population through detection of DNA ploidy may be of importance in effective management of this disease. Here we attempted to correlate aneuploid DNA patterns and their influence on biological behavior of flow-cytometry analysis of DNA ploidy which was carried out in cytologically diagnosed cases of mild (79), moderate (36), and severe (12) dysplasia, as well as “atypical squamous cells of unknown significance (ASCUS)” (57) along with controls (69), in order to understand its importance in malignant progression of disease. Cytologically diagnosed dysplasias, which were employed for DNA ploidy studies, 39 mild, 28 moderate, and 11 severe dysplasia cases were found to be aneuploid. Out of the 69 control subjects, 6 cases showed aneuploidy pattern and the rest 63 subjects were diploid. An aneuploidy pattern was observed in 8 out of 57 cases of cytologically evaluated ASCUS. The results of the followup studies showed that aberrant DNA content reliably predicts the occurrence of squamous cell carcinoma in cervical smear. Flow cytometric analysis of DNA ploidy may provide a strategic diagnostic tool for early detection of carcinoma cervix. Therefore, it is a concept of an HPV screening with reflex cytology in combination with DNA flow cytometry to detect progressive lesions with the greatest possible sensitivity and specificity.

DNA Ploidy Cytometry Testing for Cervical Cancer Screening in China (DNACIC Trial): a Prospective Randomized, Controlled Trial

“…In 2001, Melsheimer and colleagues (36) reported that flow cytometric analysis of DNA ploidy may be a potential means providing a strategic diagnostic tool for early detection of cervical cancer. Therefore, Singh et al (37) proposed a conception of combining the DNA ploidy cytometry testing, which provides qualitative information and presence of aberrant aneuploid cells in cytologic specimen through flow cytometry by measuring the DNA content, and an HPV screening with reflex cytology would be an optimal method to detect progressive lesions with the greatest possible sensitivity and specificity. In our trial, we still did HPV detection after the assigned screening testing, and obtained concur findings with previous literatures that DNA cytometry plus HPV testing had a significant higher sensitivity and positive predicted value than the conventional cytology plus HPV testing.…”

“…Approximately 320,000 of cervical cancer cases are diagnosed in the developing world every year, of which takes over 80% of all the cases of cervical cancer that are diagnosed annually worldwide (1). As thus, how the cervical cancer is sieved through effective methods during mass population screening is an essential question for global researchers investigating the effectiveness October 14, 2009; DOI: 10.1158/1078-0432.CCR-09-1689 and accuracy of currently available means-particularly for predicting the emergence of the cancer after a single round of screening.Cervical cytologic testing with the Bethesda System has proved to be one of the most successful examples of cancer screening over the simple Papanicolaou (Pap) smear test and has resulted in significant decreases in incidence and mortality from cervical cancer (2). Besides, numerous studies recommended that human papillomavirus (HPV) testing is an appropriate method when screening women in low-resource settings as a primary approach (3-6).…”

“…Approximately 320,000 of cervical cancer cases are diagnosed in the developing world every year, of which takes over 80% of all the cases of cervical cancer that are diagnosed annually worldwide (1). As thus, how the cervical cancer is sieved through effective methods during mass population screening is an essential question for global researchers investigating the effectiveness October 14, 2009; DOI: 10.1158/1078-0432.CCR-09-1689 and accuracy of currently available means-particularly for predicting the emergence of the cancer after a single round of screening.…”

Image analysis of hyperchromatic crowded cell groups in SurePath cervical cytology

“…It is widely acknowledged that quantitative DNA analysis requires a robust stoichiometric technique such as the Feulgen stain 14 . Several investigators have suggested DNA ploidy analysis as a possible cervical screening test, 15–17 as a tool for resolving low‐grade cytological abnormalities 18 and as a predictor of progressive cervical disease 19 . When employed as a primary cervical screening test for instance, DNA ploidy analysis appears to be inexpensive, can be semi‐automated, and has a sensitivity, specificity and predictive value similar to that of cervical cytology 16,17 .…”

The Indicators of Predicting Disease Outcome in HPV Carcinogenesis

“…Therefore, an increased aneuploid DNA value together with the increase in grades of cervical dysplasia are specific prognostic markers of malignancy (Kashyap & Das, 1998); flow cytometric analysis of DNA ploidy may be a potential means providing a strategic diagnostic tool for early detection of cervical cancer (Melsheimer et al 2004). The combination of DNA ploidy (determined by cytometric test) with HPV screening and cytology is an optimal method to detect progressive lesions since it has the highest sensitivity and specificity (Singh et al 2008). …”