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The Prognostic Potential of PD-L1, PD-1, CD3, CD4, and CD8 Expression in Patients with Head and Neck Cancers Depending on HPV16 Infection
by
, and
Anna Mucha-Małecka
1,*, 
Beata Biesaga
2,
Natalia Amrogowicz
3,
Aleksandra Grela-Wojewoda
4,
Mirosława Püsküllüoğlu
4
,
Marcin Przewoźnik
2,
Elżbieta Pluta
1,
Anna Patla
1,
Krzysztof Roszkowski
5
and
Krzysztof Małecki
6 1
Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Garncarska Street 11, 31-115 Cracow, Poland
2
Department of Tumor Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Garncarska Street 11, 31-115 Cracow, Poland
3
First Radiation and Clinical Oncology Department, Maria Sklodowska-Curie National Research Institute of Oncology, 44-102 Gliwice, Poland
4
Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow Branch, Garncarska Street 11, 31-115 Cracow, Poland
5
Department of Oncology, Collegium Medicum, Nicolaus Copernicus University, 85-821 Bydgoszcz, Poland
6
Department of Radiotherapy for Children and Adults, University Children’s Hospital of Cracow, Wielicka 265, 30-663 Cracow, Poland
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(11), 1771; https://doi.org/10.3390/cancers18111771
Submission received: 14 April 2026
/
Revised: 17 May 2026
/
Accepted: 20 May 2026
/
Published: 28 May 2026
(This article belongs to the Special Issue Human Papillomavirus (HPV) and Related Cancer)
Simple Summary
Head and neck squamous cell carcinoma is a common cancer with highly variable clinical outcomes, highlighting the need for reliable biomarkers that may help predict prognosis and guide treatment decisions. In this study, we investigated the expression of immune-related proteins, including programmed death-ligand 1, programmed cell death protein 1, and T-cell markers, in tumor tissues from patients in southern Poland. We also examined whether these markers were associated with human papillomavirus type 16 infection and patient outcomes. Our results show that high programmed death-ligand 1 expression was linked to poorer disease-free survival, whereas increased infiltration of immune cells was associated with better prognosis, particularly in patients without human papillomavirus infection. These findings improve understanding of the tumor immune microenvironment in head and neck cancer and may support the future development of personalized immunotherapy strategies.
Abstract
Objective: The aim of this study was to evaluate the expression of PD-L1, PD-1, CD3, CD4, and CD8 in tumor tissues of patients with head and neck squamous cell carcinoma from southern Poland, and to assess their prognostic value in relation to disease-free survival (DFS), taking into account HPV16 status and other clinical, pathological, and demographic factors. Material/Methods: This study included 155 unselected patients with head and neck squamous cell carcinoma (HNSCC) from the southern Poland region, who underwent diagnostic evaluation and surgical treatment. Formalin-fixed, paraffin-embedded (FFPE) tissue blocks were obtained from these centers. The patients were treated at the Maria Skłodowska-Curie National Research Institute of Oncology, Kraków Branch, between 1991 and 2014, with treatment approaches including induction therapy (preoperative), adjuvant therapy (postoperative), or definitive chemoradiotherapy with cisplatin. Protein expression was assessed using immunohistochemistry and quantified (TPS, CPS, H-score). Relationships between expression levels and epidemiological, clinical, and histopathological features were analyzed. Results: The results show that PD-L1 overexpression was associated with worse DFS, whereas overexpression of PD-1, CD3, CD4, and CD8 correlated with improved DFS. These associations were statistically significant in the HPV16-negative subgroup, while no such correlations were found in HPV16-positive patients. In multivariate analysis, independent prognostic factors associated with improved DFS included HPV16 infection, absence of PD-L1 overexpression, overexpression of CD4 and CD8, and combined chemoradiotherapy with cisplatin. Conclusions: These findings confirm the prognostic relevance of PD-L1, PD-1, and T-cell markers in HNSCC, particularly in HPV16-negative patients, and support further research into the use of these biomarkers in personalized treatment strategies.
