B7-H4 Expression in Precancerous Lesions of the Uterine Cervix

Biomed Res Int. 2021 Oct 5:2021:5857092. doi: 10.1155/2021/5857092. eCollection 2021.


Over 10% of patients diagnosed with cervical intraepithelial neoplasia (CIN) have no lesions detected in their cervical conization specimens. The purpose of this study was to determine the factors related to the absence of such lesions. We particularly sought to investigate whether the expression of B7-H4 in precancerous lesions and cancer of the uterine cervix plays a role in the presence or absence of residual lesions in conization specimens and whether this protein is associated with T cells (i.e., Foxp3+ regulatory T cells, CD4+, and CD8+) and interferon-γ production. Of the 807 patients with CIN treated by conization, 104 (12.9%) had no lesions in their conization specimens. Seventy-five of these patients were deemed the study group and were matched with 75 patients who did have CIN detected in their conization specimens (the control group). Immunohistochemistry and immunofluorescence staining were used to detect B7-H4, Foxp3, CD4, CD8, and interferon-γ in the 75 pairs of specimens obtained via biopsy; 20 samples were found to have chronic cervicitis, and another 20 had squamous cell carcinoma of the cervix. Menopause, the absence of human papillomavirus, low-grade histological findings, and a diagnosis of CIN1 and CIN2 on biopsy correlated with a low probability of lesions on conization specimens. B7-H4 expression was detected in 11.1% of CIN2, 46.6% of CIN3, and 70% of cervical cancer samples, but not in tissues representing chronic cervicitis or CIN1. B7-H4 expression was associated with the presence of lesions on conization specimens, increased regulatory T cells, decreased CD8+ T cells, and lower interferon-γ production. These data suggest that close follow-up and thorough reevaluation should be considered for patients diagnosed with CIN2 who are negative for B7-H4 expression on biopsy before proceeding with cervical conization.

MeSH terms

  • Adult
  • Carcinoma, Squamous Cell / pathology
  • Cervix Uteri / pathology*
  • Cytokines / metabolism
  • Female
  • Humans
  • Logistic Models
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / pathology
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1 / metabolism*
  • Young Adult


  • Cytokines
  • V-Set Domain-Containing T-Cell Activation Inhibitor 1
  • VTCN1 protein, human