PD-L1 CPS Scoring Accuracy in Small Biopsies and Aspirate Cell Blocks from Patients with Head and Neck Squamous Cell Carcinoma

Paintal, Ajit; Brockstein, Bruce

doi:10.1007/s12105-019-01097-z

Cited by 24 publications

(31 citation statements)

References 18 publications

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“…The intratumoral PD-L1 expression spatial heterogeneity may be the cause of the discordance between (randomized) diagnostic biopsies and surgical specimens, which is well known in non-small cell lung cancer [14][15][16]. Similar results were recently published by another group [17]. Future studies are needed, investigating the actual checkpoint inhibitor response corresponding with CPS scattering.…”

Section: Discussionmentioning

confidence: 67%

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

et al. 2021

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Introduction: Immune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study’s main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings. Materials and Methods: This is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies. Results: We analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (p = 0.45, p = 0.31, and p = 0.88, respectively). There was a significant (18%, 95% CI 0.65–0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity. Discussion and Conclusions: Our data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.

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Section: Discussionmentioning

confidence: 67%

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

et al. 2021

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“…19 Intratumoral heterogeneity was also described in previous studies using the Ventana SP263 antibody in HNSCC. 20,21 This poses distinct challenges for the evaluation of PD-L1 expression using small specimens such as cytology CBs or core needle biopsies. Because the evaluation is based on only small amounts of tumor tissue in these small specimens, there is always a higher risk of a false-negative result or underassessment of PD-L1 expression.…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, the agreement between cytologic and histologic specimens was higher in cases with expression of PD-L1 (ie, low and high expressors). A recent study by Paintal et al 20 investigated the PD-L1 CPS using the SP263 antibody in 20 paired HNSCC cases separated into 2 groups: a small biopsy group (core needle biopsy and FNA CB) and an excisional group (excisional biopsy and resection specimen). 20 The agreement between these 2 groups was 90% when the cutoff point was set at a CPS of 20, whereas it decreased to 70% with the threshold of CPS ≥ 1; this indicated that CPS concordance was higher in cases with higher PD-L1 expression.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of programmed death ligand 1 expression in cytology to determine eligibility for immune checkpoint inhibitor therapy in patients with head and neck squamous cell carcinoma

Liu

Williams

Stewart

et al. 2021

Cancer Cytopathology

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BACKGROUND:Immune checkpoint inhibitors targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway have recently emerged as a frontline treatment for head and neck squamous cell carcinoma (HNSCC). The evaluation of PD-L1 expression by immunohistochemistry in histologic samples is used to determine the eligibility of patients with HNSCC for immunotherapy. Patients with newly diagnosed HNSCC are frequently diagnosed by fine-needle aspiration (FNA) of lymph nodes with metastatic disease. However, the evaluation of PD-L1 expression with the proposed combined positive score (CPS) has not been well established in cytology specimens. METHODS: This study retrospectively identified 21 HNSCC patients with a known PD-L1 status from histologic specimens and matched FNA specimens with tumor cells on cell blocks (CBs). The CB sections were stained with a PD-L1 antibody (22C3 clone). All cases were scored with CPS and the tumor proportion score (TPS). RESULTS: The data showed substantial concordance between cytologic and histologic specimens for CPS (agreement, 76.2%; κ = 0.607) and TPS (agreement, 76.2%; κ = 0.607). With histology used as a reference standard, the positive predictive value was 100% for both CPS and TPS, whereas the negative predictive value was 57.1% for CPS assessments and 50% for TPS assessments. CONCLUSIONS: PD-L1 expression in HNSCC cytology samples has high concordance with paired histologic samples. PD-L1 CPS evaluation is feasible in HNSCC cytology CBs and can act as a surrogate for determining eligibility for immunotherapy in cases in which a histologic specimen is not readily available.

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“…To our knowledge, intratumoral heterogeneity has only been assessed in SCCHN by two studies: both evaluated PD-L1 expression by means of the Combined Positivity Score (CPS) in biopsy material versus the matching resection material. Results showed significant discordance in material with absent PD-L1 expression, confirming the risk of underscoring in biopsy specimen [ 121 , 125 ]. Two studies investigated PD-L1 expression on primary SCCHN versus associated (non-recurrent) lymph nodes and found a clear correlation in expression pattern [ 125 , 126 ].…”

Section: The Tme In Scchnmentioning

confidence: 92%

“…This pattern of cuffing of tumor by a PD-L1 positive immune cell infiltrate has been noted to be particularly characteristic of HPV-driven oropharyngeal carcinoma [ 118 ]. This may be a possible explanation for the underscoring of aspirate cell blocks and core biopsies relative to resected specimens and excisional biopsies is a failure to sample the peritumoral stroma in small biopsies reported in several articles [ 119 , 120 , 121 ]. Lastly, PD-L1 expression is subjected to temporal heterogeneity: immune and tumor cells are continuously shifting shape and functionality during cancer development and progression.…”

Section: The Tme In Scchnmentioning

confidence: 99%

Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives

Keukeleire

Vermassen

Hilgert

et al. 2021

Cancers

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The era of immune checkpoint inhibitors has altered the therapeutic landscape in squamous cell cancer of the head and neck (SCCHN). Our knowledge about the tumor microenvironment has fueled the research in SCCHN, leading to several well-known and less-known prognostic and predictive biomarkers. The clinical staging, p16/HPV status, and PD-L1 expression are currently the main tools for assessing the patients’ diagnosis and prognosis. However, several novel biomarkers have been thoroughly investigated, some reaching actual significant clinical contributions. The untangling of the immune infiltrate with the subtyping of tissue-associated tumor infiltrating lymphocytes, tumor-associated macrophages, and circulating blood-based biomarkers are an interesting avenue to be further explored and prospectively assessed. Although PD-L1 expression remains the most important response predictor for immune checkpoint inhibitors, several flaws impede proper assessment such as technical issues, different scoring protocol, and intra-, inter,- and temporal heterogeneity. In addition, the construction of an immune-related gene panel has been proposed as a prognostic and predictive stratification but lacks consensus. Recently, the role of microbioma have also been explored regarding its systemic and antitumor immunity. This review gives a comprehensive overview of the aforementioned topics in SCCHN. To this end, the integration of these clinically advantageous biomarkers via construction of an immunogram or nomogram could be an invaluable tool for SCCHN in future prospects.

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PD-L1 CPS Scoring Accuracy in Small Biopsies and Aspirate Cell Blocks from Patients with Head and Neck Squamous Cell Carcinoma

Cited by 24 publications

References 18 publications

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

Evaluation of programmed death ligand 1 expression in cytology to determine eligibility for immune checkpoint inhibitor therapy in patients with head and neck squamous cell carcinoma

Immuno-Oncological Biomarkers for Squamous Cell Cancer of the Head and Neck: Current State of the Art and Future Perspectives

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