Blimp-1 is a prognostic indicator for progression of cervical intraepithelial neoplasia grade 2

J Cancer Res Clin Oncol. 2022 Aug;148(8):1991-2002. doi: 10.1007/s00432-022-03993-4. Epub 2022 Apr 6.

Abstract

Background: Progression of cervical intraepithelial neoplasia (CIN) to higher grade disease is associated with persistent human papillomavirus (HPV) infection and an absence of immune-mediated regression. However, the immune microenvironment that distinguishes progression from persistent or regressing lesions has not been well defined.

Methods: A total of 69 patients under the age of 25 with high-risk HPV-positive cytology and biopsy-confirmed p16-positive CIN2 were included in the study. Biopsies were stained using 20 antibodies to a range of immune markers. Based on a 2-year follow-up, samples were analysed in "progressor" (CIN3 +) or "persister/regressor" (CIN1, 2 or normal) groups.

Results: Progression was most strongly associated with Blimp-1 positive cell staining in the lesion (P = 0.0019) and with low numbers of infiltrating CD4 cells in the dermal region beneath the lesion (P = 0.0022). The presence of CD4, CD8 and T bet-positive cells in the dermal region most strongly correlated with CD11c cells in the persister/regressor but not the progressor group.

Conclusion: High numbers of Blimp-1 + cells in CIN2 lesions may predict progression to more severe disease. Measurement of Blimp-1 may have diagnostic utility for the determination of the need to treat women with cervical pre-cancer.

Highlights: CIN2 progression is associated with high numbers of Blimp-1 positive cells in the lesion. Detection of Blimp-1 in the lesion may have utility as a prognostic test to inform the need to treat CIN2.

Keywords: Biomarkers; Cervical intraepithelial neoplasia; High-grade squamous intraepithelial lesion; Human papillomavirus; Prognosis.

MeSH terms

  • Biopsy
  • Cyclin-Dependent Kinase Inhibitor p16
  • Female
  • Humans
  • Papillomaviridae
  • Papillomavirus Infections*
  • Positive Regulatory Domain I-Binding Factor 1* / genetics
  • Prognosis
  • Tumor Microenvironment
  • Uterine Cervical Dysplasia* / diagnosis
  • Uterine Cervical Dysplasia* / pathology
  • Uterine Cervical Neoplasms* / diagnosis
  • Uterine Cervical Neoplasms* / pathology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • PRDM1 protein, human
  • Positive Regulatory Domain I-Binding Factor 1