The Association of Molecular Biomarkers in the Diagnosis of Cervical Pre-Cancer and Cancer and Risk Factors in Senegalese

Document Type: Research Articles

Authors

1 Laboratory of Cytogenetic and Reproductive Biology, Hospital Aristide-Le-Dantec, Pasteur Avenue, Dakar, Senegal.

2 Laboratory of Anatomy and Pathology, Principal Military Hospital of Dakar, Nelson Mandela Avenue, Dakar, Senegal.

3 Cancer Studies and Research Group in Senegal (GERCS), FMPO, Cheikh Anta DIOP University, Cheikh Anta Diop Avenue, Dakar, Senegal.

4 Cheikh Anta DIOP University, Department of Animal Biology, Faculty of Science and Technology, Postulant Unit of Genetic, Genomic and Bioinformatic of Infectious Diseases and Cancer, Cheikh Anta Diop Avenue, Dakar, Senegal.

5 Institut Pasteur Dakar, Pole d’immunophysiopathologie des maladies infectieuses (Pole IMI), Pasteur Avenue, Dakar, Senegal.

6 Institut Pasteur Dakar, Pole de Virologie, PO Box 220. 36, Pasteur Avenue, Dakar, Senegal.

7 Hopital Aristide LeDantec, Service de Cancerologie, Institut-Juliot-Curie, Pasteur Avenue, PO Box 3001, Dakar, Senegal.

Abstract

Background: Cervical intraepithelial neoplasia (CIN) grading is subjective and affected by substantial rates of discordance among pathologists. Although recent studies have suggested that p16INK4a may be a useful surrogate biomarker of cervical neoplasia, Ki-67 and human papillomavirus testing have also been shown to be useful in detecting neoplasia. The purpose of this study was to determine the expression of p16INK4a and Ki-67 in cervical neoplasia and its correlations with cofactors. Methods: The study involved 69 patients with and without cervical neoplasia who underwent colposcopic directed biopsy. On each patient, two samples were taken; the first was used for immunohistochemistry and the second for molecular testing, using HPV16and18 genotyping Real-Time PCR Kit. Results: The study revealed the expression level of p16INK4a and Ki-67 in a descending order, from invasive squamous cell carcinoma (SCC), CIN2/3, CIN1 and non-dysplastic lesions. Correlations showed an association between the staining of p16NK4a and Ki-67 with the increase of age (OR: 1.79 (95%IC: 0.49 – 6.55), p = 0.037) and marital status (OR: 0.17 (95%IC: 0.04 – 0.68), p = 0.003). We found that the expressions of p16INK4a and Ki-67 were significantly different between invasive SCC vs non-dysplasia (OR: 44.57 (95%IC: 4.91 – 403.91), p <0.0001). The study showed significant correlation between HPV 16and18 infection with p16 INK4a and Ki-67 expression (OR: 0.13 (95%IC: 0.03 – 0.52), p <0.0001). Strong expression of p16INK4a and Ki-67 were observed in invasive squamous cell carcinoma, moderate staining was found in CIN2/3, weak staining in CIN1 and normal histology. Conclusion: Our findings indicate that p16INK4a and Ki-67 expressions associated strongly with cervical pathology. Therefore, p16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, particularly in HPV-based screening programs.

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