Programmed death-ligand 1 (PD-L1) expression in cervical intraepithelial neoplasia and cervical squamous cell carcinoma of HIV-infected and non-infected patients.

Programmed death-ligand 1 (PD-L1) is overexpressed in cervical carcinoma, hindering tumor destruction. The aim of this study was to assess PD-L1 expression by immunohistochemistry in cervical squamous cell carcinoma (SCC) and squamous intraepithelial lesions (SILs) from human immunodeficiency virus-positive (HIV+) and human immunodeficiency virus-negative (HIV-) patients. A total of 166 SCC and SIL samples of HIV+ and HIV- patients were included and analyzed for PD-L1 expression through tumor proportion score (TPS), and results were stratified in five TPS groups using SP263 antibody and, combined positive score (CPS) using 22C3 antibody. In cohort 1 (SP263 clone), all HIV+ patients were negative for intraepithelial lesion or malignancy (NILM), and low-grade squamous intraepithelial lesions (LSILs) scored < 1; and 87.5% of high-grade squamous intraepithelial lesions (HSILs) adjacent to SCC, 19% of HSILs non-adjacent to SCC, and 69% of SCCs scored ≥ 1 (15.4% scored 5). In HIV- patients, all NILM, LSILs, HSILs adjacent to SCC, and two HSILs non-adjacent to SCC scored < 1. SCC: 88.2% scored ≥ 1 and 5.9% scored 5. In cohort 2 (SP263 and 22C3 clones), 16.7% of HIV+ patients with SCC were positive with both clones, CPS ≥ 1 (22C3) or score 5 (≥ 50%) (SP263), showing no significant differences in positivity between both clones. These results indicate that a relatively low percentage of SCCs (16.7%; both in HIV+ and in HIV- patients) express PD-L1 (TPS ≥ 50% and CPS > 1), which may be due to some samples being archival material, sample characteristics, or use of different methodologies, highlighting the need for standardization of PD-L1 assessment in SCC of the cervix. The fact that PD-L1 is overexpressed in SILs of HIV+ patients suggests potential additional applications for immunotherapy in this disease.

CD4+ and CD8+ cell populations in HIV-positive women with cervical squamous intra-epithelial lesions and squamous cell carcinoma.

INTRODUCTION: This study aimed to analyse cervical lymphocytic populations in HIV+ and HIV- patients and correlate different cervical lesions with HIV viral load and presence of high-risk HPV types. MATERIAL AND METHODS: A total of 132 histological specimens from 40 HIV+ and 72 HIV- patients were evaluated for CD4+ and CD8+ T cell distribution, presence of high-risk HPV types, peripheral blood HIV viral load and CD4+/CD8+ ratio. RESULTS: High-grade squamous intraepithelial lesions (HSIL) and squamous cell carcinoma (SCC) from HIV+ patients had lower CD4+ T cell scores compared with HIV- patients. In all lesion groups, HIV+ patients presented higher epithelial and stromal CD8+ T cell scores. HIV viral load was more often detectable in patients with SCC than in those with low-grade squamous intraepithelial lesion (LSIL) (p = 0.0409). HSIL HIV+ patients had lower circulating CD4+ T cell counts (p = 0.0434) and CD4+/CD8+ ratio (p = 0.0378) compared with LSIL HIV+ patients. High-risk HPV types other than 16 and 18/45 were more prevalent in the HIV+ group. DISCUSSION: These results support an imbalance between cervical CD4+ and CD8+ T lymphocytes of HIV+ patients with SIL and SCC, with increased CD8+ infiltrate density with lesion severity, even in patients with immune system recovery under cART.