Ane Francyne Costa

Aneuploidy detection for diagnostic and prognostic use in premalignant and malignant lesions of the uterine cervix: A systematic review

AbstractObjectiveTo systematically review the role of aneuploidy detection alone or in combination with other methods in cervical cancer screening and to evaluate the value of aneuploidy to predict the behavior of premalignant cervical lesions.MethodWe conducted a systematic review based on an electronic search for articles published between 2001 and 2020 across databases including MEDLINE/PubMed, Scopus, and Web of Science. Studies were subjected to data extraction, risk of bias, and narrative synthesis.ResultsA total of 15 articles were included in the review. Eight out of 15 studies (53.3%) were judged to be at a high or unclear risk of bias. From the 15 included studies, the index test to detect aneuploidy was DNA image cytometry (DNA‐ICM) in 12 studies and DNA flow cytometry (DNA‐FCM) in three studies. Nine studies also evaluated the performance of cytology and/or human papillomavirus (HPV) tests. For DNA‐ICM, sensitivity to detect cervical intraepithelial neoplasia or worse (CIN2+) varied between 59.0% and 95.9% and specificity varied between 54.1% and 100%. For DNA‐FCM, sensitivity varied between 27.3% to 96.8% and specificity was 100%. For cytological evaluation, sensitivity varied between 25.0% and 70.4% and specificity varied between 70.6% and 99.9%. For HPV detection, sensitivity varied between 39.4% and 100% and specificity varied between 23.3% and 84.3%.ConclusionDNA ploidy along with atypical cells findings in cytology and/or HPV detection revealed great value to detect CIN2+ lesions and to predict which lesions are more likely to progress to cervical cancer.

DNA image cytometry parameters to identify high‐grade cervical lesions

AbstractObjectiveEvaluate the performance of different DNA image cytometry (DNA‐ICM) ploidy parameters in the categorisation of DNA‐ICM results and identification of high‐grade cervical intraepithelial neoplasia or worse (≥ CIN2).MethodsCervical samples from 232 women were collected for DNA‐ICM analysis and biopsy confirmation. Five DNA parameters were used to define DNA aneuploidy: number of cells with exceeding events (EE) over 2.5cEE, 4cEE, 5cEE and 9cEE, and aneuploid stemlines. DNA‐ICM results were categorised as normal, suspicious, and abnormal.ResultsFor individual DNA ploidy parameters, sensitivity values for 50 cells with 2.5cEE, 45 cells with 4cEE, 1 cell with 9cEE and aneuploid stemline were 72.95%. 54.1%, 69.67% and 54.1%, while specificity values were 80.0%, 90.0%, 89.09% and 95.45%, respectively. For the 5cEE parameter, the sensitivity values for 1, 2, 3, 4 and 5 cells were 93.44%, 85.25%, 81.97%, 77.87% and 75.41%, while specificity values were 46.36%, 63.64%, 74.55%, 76.36% and 80.91%, respectively. For categorised DNA‐ICM results, a suspicious result showed superior sensitivity than an abnormal result (87.70% vs 82.79%, P = 0.031), but lower specificity (54.55% vs 75.45%, P < 0.001). Both types of DNA‐ICM result were statistically significantly different from a normal result (P < 0.05).ConclusionFor prognostic purposes, 1 cell with 9cEE, 45 cells with 4cEE and aneuploid stemline are the best parameters with which to categorise an abnormal DNA‐ICM result, followed by 50 cells with 2.5cEE and 4 cells with 5cEE. For screening purposes, 10 cells with 2.5cEE, 10 cells with 4cEE, and 2 cells with 5cEE are suitable parameters with which to categorise a suspicious DNA‐ICM result.

Role of DNA ploidy in diagnosis and prognosis of high‐grade cervical intraepithelial neoplasia: A prospective cohort study

AbstractObjectiveTo compare the sensitivity and specificity of DNA ploidy with cytology, human papillomavirus (HPV) testing and colposcopy in diagnosis of high‐grade cervical intraepithelial neoplasia (CIN) and to assess the role of aneuploidy in cervical lesions with the worst prognosis. A prospective observational cohort study was conducted on 254 women with altered colpocytology.MethodsColposcopy, biopsy, DNA‐ICM and HPV examinations were applied to cervical cytological and histological samples. Participants were evaluated every 6 months and divided into two groups: ‘Harm’ and ‘No‐harm’. Logistic regression and multivariate COX model were used to identify independent risk factors for diagnosis and prognosis of high‐grade CIN, and ROC curve to assess the sensitivity and specificity of methods.ResultsVariables ‘age greater than or equal to 30 years’, ‘lesion size greater than 20%’, ‘aneuploidy’ and ‘HPV 16’ were associated with diagnosis of high‐grade CIN and ‘aneuploidy’ and ‘women living with HIV’, with a worse prognosis. Agreement for colposcopy was good, with a sensitivity of 79.3% and specificity of 94.4%; DNA‐ICM and cytology were moderate, with sensitivity of 74.6% and 72.3% and specificity of 85.3% and 76.1%, respectively. High‐risk HPV and HPV 16 tests were weak, with sensitivity of 75.0% and 43.75% and specificity of 50.0% and 88.64%, respectively.ConclusionsIn relation to high‐grade CIN diagnosis, DNA‐ICM presented similar sensitivity and specificity to cytology and high‐risk HPV test when associated with HPV 16. Regarding prognosis, this research certifies that aneuploidy is considered a predictor of more severe cervical injury.