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

Asian Pac J Cancer Prev. 2020 Nov 1;21(11):3221-3227. 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.

Keywords: Biomarkers; Cervical cancer; Senegal; cofactors; human papillomavirus.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Squamous Cell / diagnosis*
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / metabolism
  • Early Detection of Cancer / methods*
  • Female
  • Follow-Up Studies
  • Humans
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Senegal / epidemiology
  • Uterine Cervical Dysplasia / diagnosis*
  • Uterine Cervical Dysplasia / epidemiology
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Neoplasms / diagnosis*
  • Uterine Cervical Neoplasms / epidemiology
  • Uterine Cervical Neoplasms / metabolism

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen