Cellular and Molecular Biology

Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma

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Abstract

Intratumor heterogeneity may contribute to the ambiguous clinical results on PD-L1 status as a predictor for immunotherapy response in patients with HNSCC. This decreases the utility of PD-L1 expression from single tumour biopsies as a predictive biomarker. In this prospective study, intratumor heterogeneity of PD-L1 expression in HNSCC was investigated with both Tumour Proportion Score (TPS) and Combined Positive Score (CPS). Thirty-three whole surgical specimens from 28 patients with HNSCC were included. PD-L1 expression in six random core biopsies from each surgical specimen was used to assess the concordance between multiple biopsies and the negative predictive value of a single negative core biopsy. With 1% cut off, 36% of the specimens were concordant with TPS and 52% with CPS. With a 50% cut-off value the concordance was 70% with TPS and 55% with CPS. Defining a tumour as positive if just a single-one of the biopsies was positive, the negative predictive value (NPV) of a single negative core biopsy was 38.9 and 0% (1% cut off), and 79.9% and 62.8% (50% cut off) for TPS and CPS, respectively. In conclusion, PD-L1 positivity varies markedly within the tumour, both with TPS and CPS, challenging the utility of this biomarker.

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Acknowledgements

J.H.R. has received a grant from Rigshospitalets research committee and from The Danish Cancer Society. S.M.B. is supported in part by grant no. P30 CA 134274-04 from the NCI and from the KFJ Foundation.

Author information

J.H.R., I.R.V., S.M.B. and J.F. contributed to the design and conduct. J.H.R., G.L., H.H.J., B.M.F. and I.W., contributed to the acquisition of the data. K.H., L.S., C.A.K., C.v.B. and I.W. contributed to the analysis, and J.H.R., I.V.R. and S.M.B. performed statistical support. All authors contributed substantial to the interpretation of data and were involved in drafting and revising the manuscript. All authors approved the final version of the manuscript.

Correspondence to Jacob H. Rasmussen.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was approved by the Regional Committee on Health Research Ethics (The Capital Region of Denmark), approval number H-16049387, and study was performed in accordance with the Declaration of Helsinki.

Data availability

The dataset used and analysed during the current study is available from the corresponding author on reasonable request.

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Rasmussen, J.H., Lelkaitis, G., Håkansson, K. et al. Intratumor heterogeneity of PD-L1 expression in head and neck squamous cell carcinoma. Br J Cancer 120, 1003–1006 (2019) doi:10.1038/s41416-019-0449-y

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