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

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.

Predictive Value of Marker of Proliferation Ki-67 and Cell Cycle Dependent Protein kinase Inhibitor P16INK4a in Cervical Biopsy to Determine Its Biological Behaviour

“…Positive predictive value =True positives / (True positives + False positives). (Halloush et al, 2008;Diouf et al, 2020;Ghosh et al, 2020). Our study also showed a significant association of Ki-67 and P16 INK4a in the evaluation of true precursor lesion and invasive cancer (χ 2 -value = 91.32* P value is <0.0001).…”

The Role of p16/Ki-67 Immunostaining, hTERC Amplification and Fibronectin in Predicting Cervical Cancer Progression: A Systematic Review

“…p16/Ki-67 IHC has been used most frequently throughout the studies. Similar to p16 and Ki-67 IHC alone, an increase in the number of DS-positive biopsy specimens was correlated with a more severe histological diagnosis [ 32 , 41 , 42 , 43 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ] and with HPV DNA positivity [ 41 , 42 , 43 , 58 , 59 , 63 ] ( Table 2 ).…”

“…p16/Ki-67 IHC has been used most frequently throughout the studies. Similar to p16 and Ki-67 IHC alone, an increase in the number of DS-positive biopsy specimens was correlated with a more severe histological diagnosis [32,[41][42][43][53][54][55][56][57][58][59][60][61][62][63] and with HPV DNA positivity [41][42][43]58,59,63] (Table 2). Ki-67 was generally expressed in combination with p16 IHC, as DS positivity.…”

Cervical Carcinoma: Oncobiology and Biomarkers

“…Despite the large number of publications dedicated to various aspects of cervical carcinogenesis, pathologists still play an important role in the development of diagnostic approaches and targeted therapies aimed at tumors characterized by a certain phenotype and the presence of biomarkers that allow the response to targeted therapy to be predicted, enabling the monitoring of response to treatment [92]. It should be emphasized the high importance of modern screening studies in various countries aimed at detecting neoplasms of the cervix using such well-known markers as P16 and Ki-67 [93][94][95][96]. Immunohistochemistry is used to study both the various stages of carcinogenesis, but also to search for effective prognostic and predictive factors.…”