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

Dominique Diouf,Cheikh Diarra,Cheikh Fall,Gora Diop,Sidy Ka,Souleymane Sarr,Oumar Faye,Aminata Ngom,Seynabou Lo,Ahmadou Dem

doi:10.31557/apjcp.2020.21.11.3221

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.

Highlights

With an estimated 570,000 cases and 311,000 deaths worldwide, cervical cancer ranks as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related death in women (Bray et al, 2018)
Recent studies have suggested that p16INK4a may be a useful surrogate biomarker of cervical neoplasia, Ki-67 and human papillomavirus testing have been shown to be useful in detecting neoplasia
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

Summary

Introduction

With an estimated 570,000 cases and 311,000 deaths worldwide, cervical cancer ranks as the fourth most frequently diagnosed cancer and the fourth leading cause of cancer-related death in women (Bray et al, 2018). Cervical cancer is rare; only a very small proportion of HPV infected women will develop a high-grade cervical intraepithelial lesions (CIN2+) and even fewer will develop cancer (Wang et al, 2015; Sundström et al, 2013). The purpose of this study was to determine the expression of p16INK4a and Ki-67 in cervical neoplasia and its correlations with cofactors. Two samples were taken; the first was used for immunohistochemistry and the second for molecular testing, using HPV16and 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. P16/Ki-67 could be considered as a suitable biomarker for cervical cancer screening, in HPV-based screening programs

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