FHIT and C-MYC expression in cervical histology and cytology as biomarkers for detecting high-grade intraepithelial neoplasia in human papillomavirus-positive women

Cancer Biomark. 2020;27(3):303-312. doi: 10.3233/CBM-182232.

Abstract

Background: The current cervical cancer screening strategies based on Papanicolaou (Pap) and Human papillomavirus (HPV) tests receive great achievement but still exhibit many limitations in clinical practice. Exploring new biomarkers as stratified management method in HPV primary screening is becoming the tendency of current research.

Methods: Immunocytochemistry (ICC) of FHIT and C-MYC were performed on exfoliated cervical cells from 197 eligible high-risk HPV positive women. Mann-Whitney U test, Pearson Chi-Square test, logistic regression analysis and receiver operating characteristic (ROC) curves were used to assess the diagnostic efficiency.

Results: ICC staining intensity of FHIT and C-MYC in high-grade cervical intraepithelial neoplasia (CIN) specimens was significantly different from low-grade CIN and normal specimens. Compared with Pap test, ROC analysis of ICC in detecting high-grade CIN resulted in a larger area under the curve (AUC) (0.805 and 0.814 vs 0.723, p< 0.001). FHIT achieved higher sensitivity than Pap test (79.41% vs 66.67%, p= 0.04). Logistic regression analysis of the combination of two biomarkers led to higher AUC value, specificity and PPV than any single biomarker.

Conclusions: The utility of FHIT and C-MYC ICC analysis in cervical exfoliated cells of HPV-positive women displayed superior diagnostic potential and may improve clinical performance of cervical cancer screening.

Keywords: CIN; Biomarker; FHIT; C-MYC; Immunocytochemistry.

MeSH terms

  • Acid Anhydride Hydrolases / biosynthesis*
  • Acid Anhydride Hydrolases / genetics
  • Acid Anhydride Hydrolases / metabolism
  • Adult
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Papillomaviridae / isolation & purification*
  • Papillomavirus Infections / genetics
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Proto-Oncogene Proteins c-myc / biosynthesis*
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Uterine Cervical Dysplasia / genetics
  • Uterine Cervical Dysplasia / metabolism*
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Dysplasia / virology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • MYC protein, human
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-myc
  • fragile histidine triad protein
  • Acid Anhydride Hydrolases