Immunohistochemical expression of programmed death-ligand 1 associated with human papillomavirus-driven high-grade cervical intraepithelial neoplasia in South African women

Abstract

BACKGROUND : Cervical cancer is the second most prevalent malignancy among South African women, with high-risk human papillomavirus (HPV) infection as a critical risk factor. HPV plays a central role in cervical carcinogenesis, particularly in high-grade squamous intraepithelial lesions (HSIL). Increased programmed death ligand 1 (PD-L1) expression has been implicated in cervical carcinoma tumorigenesis. Using immunohistochemistry, this study investigated the correlation between high-risk HPV-driven cervical intraepithelial neoplasia (CIN) and PD-L1 expression. METHODS : An analytical cross-sectional study was conducted on archival tissue from the Department of Anatomical Pathology, University of Pretoria (2018–2021). Formalin-fixed paraffin-embedded tissues from loop electrosurgical excisions, cone biopsies, punch biopsies, and polypectomies were analysed. PD-L1 expression was assessed using the combined proportion score (CPS). Three pathologists independently evaluated histological grade, p16 immunohistochemistry, and PD-L1 expression. RESULTS : Among 108 cases (mean age: 37.36 years), 89.8% were CIN 3, 9.3% CIN 2, and 0.9% CIN 2–3. p16 was positive in 97.2% of cases. PD-L1 expression (CPS ≥ 1) was observed in 9.3% of cases, with a mean CPS of 1.57%. No significant association was found between PD-L1 expression and CIN grade (p = 0.6433, Cramer’s V = 0.1191) or between PD-L1 and p16 positivity (p = 1, Cramer’s V = 0.05976). CONCLUSIONS : This study demonstrates no correlation between PD-L1 expression and high-risk HPV-driven high-grade CIN. These findings suggest that immune checkpoint inhibition targeting PD-L1 may have limited therapeutic relevance in HSIL among South African women.

SIMPLE SUMMARY High-grade cervical intraepithelial neoplasia is a precursor to cervical cancer and is caused by persistent infection with high-risk human papillomavirus (HPV). Immune checkpoint proteins such as programmed death-ligand 1 (PD-L1) play a role in tumour immune evasion, but their significance in pre-invasive cervical lesions is unclear. In this laboratory-based study from a South African public-sector pathology service, we assessed PD-L1 expression in HPV-driven high-grade cervical intraepithelial neoplasia using routine tissue samples. PD-L1 expression was uncommon and showed no association with lesion grade, suggesting a limited role for PD-L1 in the early stages of HPV-related cervical disease.