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Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania

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dc.creator Zuberi, Zavuga
dc.creator Mremi, Alex
dc.creator Chilongola, Jaffu
dc.creator Semango, George
dc.creator Sauli, Elingarami
dc.date 2021-11-10T06:00:29Z
dc.date 2021-11-10T06:00:29Z
dc.date 2021-10-27
dc.date.accessioned 2022-10-25T09:20:58Z
dc.date.available 2022-10-25T09:20:58Z
dc.identifier https://doi.org/10.1371/journal.pone.0259096
dc.identifier https://dspace.nm-aist.ac.tz/handle/20.500.12479/1394
dc.identifier.uri http://hdl.handle.net/123456789/95328
dc.description This research article published by PLOS ONE, 2021
dc.description Introduction Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol’s iodine and Pap test are being used as the standard screening/ diagnostic methods. Methods This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. Results A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher’s exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman’s rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The ageadjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059–1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008–1.085, p = 0.015)]. Importantly, thediagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Conclusion Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.
dc.format application/pdf
dc.language en
dc.publisher PLOS ONE
dc.subject Research Subject Categories::NATURAL SCIENCES
dc.title Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania
dc.type Article


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