Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer.

Background: The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear.

Methods: In this phase 3, open-label trial, we randomly assigned participants with locally advanced HNSCC in a 1:1 ratio to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group). Standard care was surgery and adjuvant radiotherapy with or without concomitant cisplatin.

Surgery of T1/2 N0 M0 glottic cancer results in a better laryngeal preservation time compared to radiotherapy in a large German patient cohort.

Objective: This retrospective study examined overall survival (OS), recurrence free survival (RFS), and laryngeal preservation time in a large cohort of 663 patients with T1/2 N0 M0 glottic cancer after transoral laser or open surgery vs radiotherapy.

Methods: A total of 595 surgically treated patients and 68 individuals after definitive radio(chemo)therapy (R (C)-T) were studied. Patient characteristics including sociological, surgical, and pathological data, OS and RFS as well as laryngeal preservation time were recorded and compared between various groups/cohorts.

[Medical tumor therapy for head and neck cancer: between standardization and personalization].

In the field of systemic cancer therapy for head and neck neoplasms, new approvals have led to several changes in treatment standards, primarily in the palliative situation. At the same time, molecular biomarkers have been established that can contribute to therapeutic decision-making in addition to clinical factors. These developments are summarized, and potential strategies to resolve the tension between standardization and personalization are described.

Identification of B Cell Subpopulations with Pro- and Anti-Tumorigenic Properties in an Immunocompetent Mouse Model of Head and Neck Squamous Cell Carcinoma.

Due to their high developmental diversity and different regulatory and functional roles, B cell subpopulations can promote or inhibit tumor growth. An orthotopic murine HNSCC model was applied to investigate the B cell composition and function in HNSCCs. Using flow cytometry approaches, cells from the spleen, lymph nodes and tumors were analyzed.

Characterization of the adaptive immune response in a mouse model for HPV-positive head and neck squamous cell carcinoma with implications to human disease.

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with a poor prognosis for survival. Risk factors include alcohol and tobacco abuse and infection with human papilloma virus (HPV). To enhance anti-tumor immune responses immunotherapeutic approaches are approved for recurrent metastatic disease but only approx.

5-Aza-2'-deoxycytidin (Decitabine) increases cancer-testis antigen expression in head and neck squamous cell carcinoma and modifies immune checkpoint expression, especially in CD39-positive CD8 and CD4 T cells.

Failure of immunotherapy in head and neck squamous cell carcinoma (HNSCC) patients represents an unmet need to augment leverage of adaptive immunity. Immunogenic cancer-testis antigen (CTA) expression as well as lymphocyte differentiation and function are regulated by DNA methylation. Therefore, epigenetic therapy via inhibition of DNA-Methyltransferases by 5-Aza-2'-deoxycytidine (DAC) serves a promising adjuvant in immunotherapy.

Immune checkpoint expression on tumor-infiltrating lymphocytes (TIL) is dependent on HPV status in oropharyngeal carcinoma (OPSCC) - A single-cell RNA sequencing analysis.

Introduction: A substantial proportion of head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is associated with human papillomavirus (HPV), resulting in distinct molecular phenotypes. In this study, we investigated differential immune checkpoint molecule (ICM) expression by HPV status using RNA sequencing data to identify additional ICM targets that may complement anti-PD1 antibodies.

Material And Methods: RNA sequencing was performed on 51 OPSCC cases and validated using the TCGA HNSCC dataset.

[Immunotherapy for head and neck tumors : Updates from the 2024 ASCO Annual Meeting].

Immunotherapeutic approaches are now established in the treatment of various tumor entities, including head and neck squamous cell carcinoma (HNSCC). PD‑1 antibodies are currently approved for HNSCC with palliative intent but are increasingly being investigated in studies with curative objectives, e.g.

Treatment regimens for laryngeal and hypopharyngeal squamous cell carcinoma: a "real life" multicenter study of 2307 patients.

Objective: This retrospective multicenter study aimed to evaluate surgical versus conservative treatment in patients with hypopharyngeal and laryngeal cancer under real world conditions.

Methods: This study included 2307 patients diagnosed with hypopharyngeal or laryngeal squamous cell carcinoma (SCC) in five German tertiary head and neck centers between 01/2004 and 12/2014. Overall, 783 patients with advanced SCC consecutively underwent laryng(opharyng)ectomy (L(P)E).

Multi-omics analysis of overexpressed tumor-associated proteins: gene expression, immunopeptide presentation, and antibody response in oropharyngeal squamous cell carcinoma, with a focus on cancer-testis antigens.

Introduction: The human leukocyte antigen complex (HLA) is essential for inducing specific immune responses to cancer by presenting tumor-associated peptides (TAP) to T cells. Overexpressed tumor associated antigens, mainly cancer-testis antigens (CTA), are outlined as essential targets for immunotherapy in oropharyngeal squamous cell carcinoma (OPSCC). This study assessed the degree to which presentation, gene expression, and antibody response (AR) of TAP, mainly CTA, are correlated in OPSCC patients to evaluate their potential as immunotherapy targets.

Barbed suture in neck dissection: a randomized clinical study on efficacy, safety and aesthetic outcome.

Purpose: The resection of lymph nodes/neck dissection is a typical part of the surgical treatment of head and neck malignancies. The aim of this study was to compare subcutaneous closure using single knotted, braided suture (Vicryl, standard arm) with continuous self-locking, monofilament barbed suture (V-Loc, experimental arm).

Methods: Neck Lock was a randomized clinical trial at a single tertiary referral center.

Quantification of human papillomavirus cell-free DNA from low-volume blood plasma samples by digital PCR.

The incidence rate of human papillomavirus-driven oropharyngeal cancer (HPV-OPC) is increasing in countries with high human development index. HPV cell-free DNA (cfDNA) isolated from 3 to 4 mL blood plasma has been successfully used for therapy surveillance. A highly discussed application of HPV-cfDNA is early detection of HPV-OPC.

Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial.

Background: Despite multimodal therapy, 5-year overall survival for locally advanced head and neck squamous cell carcinoma (HNSCC) is about 50%. We assessed the addition of pembrolizumab to concurrent chemoradiotherapy for locally advanced HNSCC.

Methods: In the randomised, double-blind, phase 3 KEYNOTE-412 trial, participants with newly diagnosed, high-risk, unresected locally advanced HNSCC from 130 medical centres globally were randomly assigned (1:1) to pembrolizumab (200 mg) plus chemoradiotherapy or placebo plus chemoradiotherapy.

INHBA is Enriched in HPV-negative Oropharyngeal Squamous Cell Carcinoma and Promotes Cancer Progression.

Unlabelled: Patients with oropharyngeal squamous cell carcinoma (OPSCC) caused by human papilloma virus (HPV) exhibit a better prognosis than those with HPV-negative OPSCC. This study investigated the distinct molecular pathways that delineate HPV-negative from HPV-positive OPSCC to identify biologically relevant therapeutic targets. Bulk mRNA from 23 HPV-negative and 39 HPV-positive OPSCC tumors (n = 62) was sequenced to uncover the transcriptomic profiles.

Machine Learning-assisted immunophenotyping of peripheral blood identifies innate immune cells as best predictor of response to induction chemo-immunotherapy in head and neck squamous cell carcinoma - knowledge obtained from the CheckRad-CD8 trial.

Purpose: Individual prediction of treatment response is crucial for personalized treatment in multimodal approaches against head-and-neck squamous cell carcinoma (HNSCC). So far, no reliable predictive parameters for treatment schemes containing immunotherapy have been identified. This study aims to predict treatment response to induction chemo-immunotherapy based on the peripheral blood immune status in patients with locally advanced HNSCC.

Regional outcome disparities in German head and neck cancer patients: Shorter survival in Eastern Germany.

Introduction: Demographics are important prognostic factors in malignant diseases. A nationwide analysis concerning the prognostic impact of demographics in head and neck cancer (HNC) patients (HNCP) has not been performed previously.

Methods: A retrospective analysis of data from the Center for Cancer Registry Data (ZfKD) and the Federal Statistical Office (Destatis) between 2002 and 2017 was performed.

Demographics and access to head and neck cancer care in rural areas compared to urban areas in Germany.

Background: Demographic development in rural and urban areas differs substantially. Demographics and access to specialized head and neck cancer centers may affect head and neck cancer patients' (HNCP) outcomes. Here, we compare epidemiological indicators and outcomes of HNCP in rural and urban Germany.

Influence of Bruton's Tyrosine Kinase (BTK) on Epithelial-Mesenchymal Transition (EMT) Processes and Cancer Stem Cell (CSC) Enrichment in Head and Neck Squamous Cell Carcinoma (HNSCC).

Constitutively active kinases play a crucial role in carcinogenesis, and their inhibition is a common target for molecular tumor therapy. We recently discovered the expression of two oncogenic isoforms of Bruton's Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC), Btk-p80 and BTK-p65. However, the precise role of BTK in HNSCC remains unclear.

Liquid biopsy: an examination of platelet RNA obtained from head and neck squamous cell carcinoma patients for predictive molecular tumor markers.

Aim: Recently, a tumor cell-platelet interaction was identified in different tumor entities, resulting in a transfer of tumor-derived RNA into platelets, named further "tumor-educated platelets (TEP)". The present pilot study aims to investigate whether such a tumor-platelet transfer of RNA occurs also in patients suffering from head and neck squamous cell carcinoma (HNSCC).

Methods: Sequencing analysis of RNA derived from platelets of tumor patients (TPs) and healthy donors (HDs) were performed.

[Patient-reported outcomes in head and neck cancer treatment: relevance, challenges, and benefit].

Next to overall survival, quality of life is becoming more and more pivotal for cancer patients. The various domains of quality of life are complex and have different value to each patient. However, not only patients but also health care professionals, the pharmaceutical industry, and regulatory bodies ask: How can quality of life be reliably ascertained in clinical trials? For this purpose, carefully developed and validated specific questionnaires are needed: the patient-reported outcome measures (PROMs).

[Immunotherapy in the context of other head and neck cancer treatment modalities-highlights of the ASCO and ESMO annual meeting 2022].

Immunotherapeutic agents are nowadays established for treatment of a wide variety of tumor entities, including squamous cell carcinoma of the head and neck region. Originally used in the palliative setting, these are increasingly administered with curative intent, e.g.

The HLA ligandome of oropharyngeal squamous cell carcinomas reveals shared tumour-exclusive peptides for semi-personalised vaccination.

Background: The immune peptidome of OPSCC has not previously been studied. Cancer-antigen specific vaccination may improve clinical outcome and efficacy of immune checkpoint inhibitors such as PD1/PD-L1 antibodies.

Methods: Mapping of the OPSCC HLA ligandome was performed by mass spectrometry (MS) based analysis of naturally presented HLA ligands isolated from tumour tissue samples (n = 40) using immunoaffinity purification.

Treatment dependent impact of plasma-derived exosomes from head and neck cancer patients on the epithelial-to-mesenchymal transition.

Background: Epithelial to mesenchymal transition (EMT) is a key process in carcinogenesis of head and neck squamous cell carcinoma (HNSCC), contributing to tumor invasiveness, distant metastasis, and recurrence. Exosomes are known mediators and regulators of EMT. Here, we analyze the impact of exosomes that were primed by conventional therapy on EMT modulation.

BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression.

Here, we describe the expression of Bruton's Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic.