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. 2023 Feb 14;24(4):3838.
doi: 10.3390/ijms24043838.

Loco-Regional Control and Sustained Difference in Serum Immune Protein Expression in Patients Treated for p16-Positive and p16-Negative Head and Neck Squamous Cell Carcinoma

Karl Sandström  1 , Ylva Tiblom Ehrsson  1 , Felix Sellberg  2 , Hemming Johansson  3 , Göran Laurell  1
Affiliations

Loco-Regional Control and Sustained Difference in Serum Immune Protein Expression in Patients Treated for p16-Positive and p16-Negative Head and Neck Squamous Cell Carcinoma

Karl Sandström et al. Int J Mol Sci. .

Abstract

The main prognostic factors for patients with head and neck cancer are the tumour site and stage, yet immunological and metabolic factors are certainly important, although knowledge is still limited. Expression of the biomarker p16INK4a (p16) in oropharyngeal cancer tumour tissue is one of the few biomarkers for the diagnosis and prognosis of head and neck cancer. The association between p16 expression in the tumour and the systemic immune response in the blood compartment has not been established. This study aimed to assess whether there is a difference in serum immune protein expression profiles between patients with p16+ and p16- head and squamous cell carcinoma (HNCC). The serum immune protein expression profiles, using the Olink® immunoassay, of 132 patients with p16+ and p16- tumours were compared before treatment and one year after treatment. A significant difference in the serum immune protein expression profile was observed both before and one year after treatment. In the p16- group, a low expression of four proteins: IL12RB1, CD28, CCL3, and GZMA before treatment conferred a higher rate of failure. Based on the sustained difference between serum immune proteins, we hypothesise that the immunological system is still adapted to the tumour p16 status one year after tumour eradication or that a fundamental difference exists in the immunological system between patients with p16+ and p16- tumours.

Keywords: P16; cytokines; head and neck cancer; protein expression; serum.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Forest plot on the effect of the p16 status on protein expression at baseline. Bars represent the confidence interval (CI), and the box represents the median.
Figure 2
Figure 2
Univariable risk of treatment failure. Serum immune protein levels at baseline with an effect on the cumulative incidence of failure. Regression analysis. NPX values for each protein were grouped into a low and high group using the median as the cut-off. X-axis shows the odds ratio. Hazard ratio (HR). Bars represent the confidence interval (CI), and the box represents the median.
Figure 3
Figure 3
The interaction between p16 and proteins in relation to treatment failure. (˂ Median = Low values, ≥ High values. Y-axis: Cumulative incidence of failure. X-axis: Months since end of treatment).
Figure 4
Figure 4
Forest plot on the effect of the p16 status on protein expressions at 12 months after the primary treatment in patients without failure within two years of the primary treatment. Only proteins with significant differences are shown, with increasing p-values from left to right (CXCL13 p = 0.000, HGF p = 0.042). Bars represent the confidence interval (CI), and the box represents the median.
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