{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:01:33Z","timestamp":1787022093278,"version":"build-2736575974"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T00:00:00Z","timestamp":1635292800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"World Bank under the CREATES-FNS project at NM-AIST","award":["02090107-048-301-4001-P044-J01S01-C42"],"award-info":[{"award-number":["02090107-048-301-4001-P044-J01S01-C42"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"\n Introduction<\/jats:title>\n 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\u2019s iodine and Pap test are being used as the standard screening\/ diagnostic methods.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 145 patients, with a mean age of 52.1 \u00b1 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\u2019s exact test,\n p<\/jats:italic>\n <0.001). Moreover, there was a strong positive correlation between p16\/TOP2A and cancerous cervical lesions (Spearman\u2019s rank correlation coefficients = 0.833 and 0.687,\n p<\/jats:italic>\n = 0.006 and 0.005, respectively). The age-adjusted 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\u20131.232,\n p<\/jats:italic>\n <0.001) and TOP2A: OR = 1.046 (95% CI: 1.008\u20131.085,\n p<\/jats:italic>\n = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2%\n versus<\/jats:italic>\n 77.6%, accuracy: 92.8%\n versus<\/jats:italic>\n 87.8%, respectively).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0259096","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T13:34:41Z","timestamp":1635341681000},"page":"e0259096","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"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"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0150-2005","authenticated-orcid":true,"given":"Zavuga","family":"Zuberi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7226-0168","authenticated-orcid":true,"given":"Alex","family":"Mremi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaffu O.","family":"Chilongola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Semango","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elingarami","family":"Sauli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,27]]},"reference":[{"issue":"6","key":"pone.0259096.ref001","doi-asserted-by":"crossref","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"F Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"issue":"5","key":"pone.0259096.ref002","doi-asserted-by":"crossref","first-page":"E359","DOI":"10.1002\/ijc.29210","article-title":"Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012","volume":"136","author":"J Ferlay","year":"2015","journal-title":"Int J Cancer"},{"key":"pone.0259096.ref003","unstructured":"International Agency for Research on Cancer. 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