Langerhans cells and epithelial cell modifications in cervical intraepithelial neoplasia: correlation with human papillomavirus infection
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J Viac1, I Guérin-Reverchon, Y Chardonnet
1INSERM U 209, CNRS DO 601, Hôpital E. Herriot, Lyon, France.
Insights
Cervical intraepithelial neoplasia (CIN) involves immune cell changes and altered EGF receptor expression, potentially impairing immune surveillance. Human papillomavirus (HPV) infection correlates with these immune alterations in CIN lesions.
Area of Science:
- Gynecologic Pathology
- Immunology
- Oncology
Background:
- Cervical intraepithelial neoplasia (CIN) grades II and III are precancerous lesions.
- Human papillomavirus (HPV) infection is a primary cause of cervical cancer.
- Understanding the interplay between HPV, immune cells, and epithelial changes is crucial for disease progression insights.
Purpose of the Study:
- To investigate the distribution and phenotype of immunocompetent cells (Langerhans cells, T cells, NK cells) in CIN II/III.
- To determine alterations in epidermal growth factor (EGF) receptor and beta 2-microglobulin expression.
- To correlate these changes with HPV infection status.
Main Methods:
- Analysis of 18 cervical intraepithelial neoplasia (CIN) grade II and III lesions.
- Immunohistochemical assessment of immunocompetent cells and molecular markers.
- Human papillomavirus (HPV) DNA typing using biotinylated probes.
Main Results:
- CIN lesions showed reduced Langerhans cells and dense immune infiltrates.
- Enhanced expression of epidermal growth factor (EGF) receptors and reduced beta 2-microglobulin reactivity were observed.
- HPV infection did not induce HLA-DR expression in infected epithelial cells, impairing antigen presentation.
Conclusions:
- Altered immune cell distribution and expression of EGF receptors and beta 2-microglobulin in CIN lesions are associated with HPV infection.
- The lack of HLA-DR expression in infected cells hinders antigen presentation, potentially reducing immune surveillance.
- These immune dysregulations may contribute to the progression and severity of CIN lesions.
Abstract:
The study of a series of 18 cervical intraepithelial neoplasia (CIN) grade II and III was aimed at determining the distribution and phenotype of immunocompetent cells (Langerhans cells, T and NK cells) and the alteration in the expression of EGF receptors and beta 2-microglobulin in correlation with human papillomavirus (HPV) infection (viral antigen and DNA typing with biotinylated probes). These lesions were characterized by a reduced number of Langerhans cells and a dense infiltrate. HPV infection did not induce HLA-DR expression in the infected epithelial cells. We observed an enhanced expression of epidermal growth factor (EGF) receptors by epithelial cells and a reduced beta 2-microglobulin reactivity by both epithelial and immunocompetent cells. Most of CIN showed foci of infected cells. No significant differences were observed in immunological markers of CIN harboring benign HPV 6/11 DNA or oncogenic HPV 16/18 DNA. Viral antigen was not detected in these lesions. These changes in the epithelial cells of CIN and their microenvironment associated to the lack of HLA-DR expression in the infected cells hamper the squamous epithelial cells to function as antigen presenting cells. This may facilitate a decrease in the immunological surveillance and may contribute to the severity of such lesions.