Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma.
OBJECTIVE
Oropharyngeal squamous cell carcinoma (OSCC) has been recognized as an immunosuppressive disease. Various mechanisms have been proposed for immune escape, including dysregulation of immune checkpoints such as the PD-1:PD-L1 pathway. We investigated the expression of programmed cell death-ligand 1 (PD-L1) in HPV-negative and HPV-positive OSCC to determine its prevalence and prognostic relevance.


METHODS
Using immunohistochemistry, 133 cases of OSCC were evaluated for expression of PD-L1. Formalin-fixed paraffin-embedded tumor samples were stained with monoclonal antibody (clone 5H1) to PD-L1. PD-L1 positivity was defined as membrane staining in ≥20% of tumor cells. Correlations between PD-L1 expression and HPV status and survival parameters were analyzed.


RESULTS
Of the 133 patients, 68% showed PD-L1 expression, and 67% of patients were positive for p16 expression by immunohistochemistry. No significant difference in PD-L1 expression was observed between HPV(-) and HPV(+) tumors (61% vs. 71%, p=0.274). No significant difference in age, gender, smoking history, location of tumor origin, or stage was observed according to PD-L1 status. With a median follow-up period of 44 months, older age (≥65) (p=0.017) and T3-4 stage (p<0.001) were associated with poor overall survival (OS), whereas PD-L1 expression did not affect OS in univariate and multivariate analysis.


CONCLUSIONS
PD-L1 expression was observed in the majority of OSCC patients regardless of HPV status. Further large prospective studies are required to determine the role of PD-L1 expression as a prognostic or predictive biomarker, and clinical studies of immune checkpoint inhibitors in OCSS are warranted regardless of HPV status.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hae Su
HS
Kim
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Ji Yun
JY
Lee
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sung Hee
SH
Lim
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Keunchil
K
Park
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jong-Mu
JM
Sun
Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young Hyeh
YH
Ko
Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chung-Hwan
CH
Baek
Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young-ik
YI
Son
Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Han Sin
HS
Jeong
Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yong Chan
YC
Ahn
Division of Hematology-Oncology, Department of Internal Medicine, Soonchunhyang University Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.
Min-Young
MY
Lee
Department of Pathology, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea.
Mineui
M
Hong
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Myung-Ju
MJ
Ahn
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000175:diagnosis*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000150:complications* / Q000175:diagnosis*; D030361:Papillomavirus Infections / Q000150:complications*; D011379:Prognosis
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
Human papillomavirus (HPV); Immune checkpoint inhibitor; Immune therapy; Oropharyngeal Neoplasms; Programmed death ligand-1 (PD-L1)