Prognostic and predictive role of soluble programmed death ligand-1 in head and neck cancer

Molga-Magusiak, Maria; Rzepakowska, Anna; Żurek, Michał; Kotuła, Iwona; Demkow, Urszula; Niemczyk, Kazimierz

doi:10.1016/j.bjorl.2023.02.005

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Brazilian Journal of Otorhinolaryngology

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Sumário

Original article • Braz. j. otorhinolaryngol. 89 (3) • May-Jun 2023 • https://doi.org/10.1016/j.bjorl.2023.02.005 copy

Prognostic and predictive role of soluble programmed death ligand-1 in head and neck cancer

Authorship SCIMAGO INSTITUTIONS RANKINGS

Highlights

sPD-L1 is potential predictive biomarker for differentiation of malignant lesions in head and neck region.
Significantly higher levels of sPD-L1 are detected in malignant tumors.
Higher levels of sPD-L1 proves reliable prognostic biomarker in predicting early recurrence of laryngeal cancer.
Increased sPD-L1 correlates with poor disease-free survival in head and neck cancer.

Abstract

Objectives

The aim of the study was to investigate clinical significance of soluble PD-L1 (sPD-L1) serum level in head and neck cancer and to evaluate its role as a possible prognostic and predictive biomarker.

Methods

A prospective analysis of sPD-L1 levels in 60 patients diagnosed and treated due to malignant and non-malignant lesions in the region of head and neck was performed in peripheral blood by an ELISA test.

Results

The range of sPD-L1 in the study group was 0.16-1.63 ng/mL, mean 0.64 ± 0.32. There were no differences in the mean sPD-L1 regarding patients’ age, sex, and the localization of the lesion. Statistically significant difference was revealed in the average sPD-L1 level (p = 0.006) depending on the histopathological advancement of the lesions, 0.704 ± 0.349 and 0.512 ± 0.177 respectively in the malignant and benign group. The separate analysis of laryngeal lesions confirmed statistical difference in sPD-L1 (p = 0.002) for the malignant lesions (0.741 ± 0.353) compared with the benign (0.489 ± 0.175). The sPD-L1 level of 0.765 ng/mL or higher, revealed 35% sensitivity and 95.5% specificity for the diagnosis of head and neck malignant lesions (AUC = 0.664, 95% CI 0.529‒0.8, p-value = 0.039). The 1-year DFS was 83.3% in the group of patients with low sPD-L1 levels (< 0.765 ng/mL) and 53.8% in patients with high sPD-L1 (≥0.765 ng/mL). The 2-year OS were 68% and 69.2% respectively in both groups. The log-rank test confirmed statistically significant prognostic value of sPD-L1 level for 1-year DFS (p-value = 0.035).

Conclusions

sPD-L1 is a promising prognostic and early recurrence predictive biomarker for head and neck cancers, most significantly for laryngeal lesions.

Level of evidence

Keywords
Soluble biomarker; Programmed death ligand 1; Head and neck cancer; Laryngeal cancer; sPD-L1

	All patients	Malignant lesions	Benign lesions
Mean age (years) ± SD	63.47 ± 14.21	68.75 ± 12.05	52.9 ± 12.34
Sex
Female	17	10	7
Male	43	30	13
Site
Larynx	46	31	15
Oropharynx	9	8	1
Salivary gland	3	1	2
Neck	2	0	2

	Number of patients (n)	Serum sPD-L1 ng/mL (Mean, SD)	p-Value
All patients	60	0.64 ± 0.315	0.728^a a Independent two-sample t-test.
Age ≥ 66	31	0.654 ± 0.353
Age < 66	29	0.625 ± 0.274
Sex
Female	17	0.632 ± 0.282	0.889^b b Mann-Whitney U test.
Male	43	0.643 ± 0.33	0.889^b b Mann-Whitney U test.
Location (all lesions)			0.302^c c Kruksal-Wallis one-way analysis of variance.
Larynx	46	0.659 ± 0.327
Oropharynx	9	0.529 ± 0.322
Salivary gland	3	0.737 ± 0.05
Neck (brachial cleft cyst)	2	0.565 ± 0.205
Histological types (all lesions)			0.176^c c Kruksal-Wallis one-way analysis of variance.
Invasive cancer
HGD	34	0.7 ± 0.364
LGD	6	0.727 ± 0.276
No-dysplasia	18	0.504 ± 0.166
Histological types (laryngeal lesions)			0.029 ^c c Kruksal-Wallis one-way analysis of variance.
Invasive cancer	25	0.744 ± 0.374
HGD	6	0.727 ± 0.276
LGD	1	0.83
No-dysplasia	14	0.465 ± 0.153
Histological groups (all lesions)			0.006 ^a a Independent two-sample t-test.
Malignant: invasive cancer + HGD	40	0.704 ± 0.349
Benign: LGD + No-dysplasia	20	0.512 ± 0.177
Histological groups (laryngeal lesions)			0.002 ^a a Independent two-sample t-test.
Malignant: invasive cancer + HGD	31	0.741 ± 0.353
Benign: LGD + No-dysplasia	15	0.489 ± 0.175
Grade (malignant lesions n = 40)			0.635^c c Kruksal-Wallis one-way analysis of variance.
G1	3	0.627 ± 0.046
G2	20	0.62 ± 0.347
G3	2	0.91 ± 0.467
Stage - T (malignant lesions n = 40)			0.307^b b Mann-Whitney U test.
Tis + T1+T2	21	0.756 ± 0.32
T3+T4	19	0.647 ± 0.38
Stage - N (malignant lesions n = 40)			0.069^b b Mann-Whitney U test.
N0	31	0.758 ± 0.354
N1+N2+N3	9	0.518 ± 0.272
Stage - M (malignant lesions n = 40)			0.124^a a Independent two-sample t-test.
M0	39	0.723 ± 0.346
M1	1	0.17
Smoking (all lesions)			0.97^b b Mann-Whitney U test.
No	23	0.634 ± 0.316
Yes	37	0.644 ± 0.32
GERD (all lesions)			0.429^a a Independent two-sample t-test.
No	50	0.649 ± 0.34
Yes	10	0.596 ± 0.143

Variable	DFS			OS
	HR	95% CI	p-Value	HR	95% CI	p-Value
sPD-L1 ≥ 0.765 ng/mL	2.895	0.95‒8.82	0.062	1.443	0.385‒5.41	0.586
Age	1.035	0.98‒1.09	0.184	1.057	0.99‒1.13	0.083
Male sex	1.08	0.27‒4.31	0.916	1.017	0.18‒5.61	0.985
Stage - T (Tis, T1, T2 vs. T3, T4)	1.403	0.5‒3.93	0.519	2.382	0.67‒8.42	0.178
Stage - N (N0 vs. N1, N2, N3)	3.93	1.28‒12.1	0.017	6.086	1.72‒21.49	0.005
Smokers vs. non-smokers	0.998	0.31‒3.23	0.998	0.977	0.24‒4.01	0.975

Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Sede da Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico Facial, Av. Indianópolia, 1287, 04063-002 São Paulo/SP Brasil, Tel.: (0xx11) 5053-7500, Fax: (0xx11) 5053-7512 - São Paulo - SP - Brazil
E-mail: revista@aborlccf.org.br

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[1] ⁎ Corresponding author. E-Mail:arzepakowska@wum.edu.pl (A. Rzepakowska).