Financial instability, insurance, and transportation influence timely head and neck cancer care in the United States: Patient and healthcare worker perspectives.

Introduction: Delays in head and neck cancer (HNC) diagnosis and treatment and financial burdens of care are often rooted in social determinants of health (SDOH), such as financial instability, socioeconomic status (SES), health insurance status, and transportation barriers. While these factors are well recognized, their underlying impact on access to care remains underexplored; this qualitative study aims to investigate how these SDOH facilitate or hinder HNC care through insights from patients and healthcare workers (HCWs) in the United States, to identify targets for intervention.

Methods: Semi-structured interviews were conducted with patients with newly diagnosed HNC, and HCWs caring for these patients, between June 2022 and July 2023.

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.

Mixing it up: boosting responses with immunotherapy combinations.

Whether combination neoadjuvant immunotherapy can enhance response in patients with head and neck cancer remains unclear. Recently, Li et al. demonstrated improved responses with neoadjuvant anti-PD-1+CTLA-4 or anti-PD-1+LAG-3 compared with anti-PD-1 monotherapy.

Easing cisplatin's toll in nasopharyngeal carcinoma.

Anti-PD-1 immune checkpoint inhibitors improve outcomes in relapsed/metastatic nasopharyngeal carcinoma (NPC). In this issue of Cancer Cell, Xu et al. achieved favorable outcomes by incorporating nivolumab into standard therapy for locally advanced NPC while removing chemotherapy from the radiation phase.

Neoadjuvant Therapy for Mucosal Head and Neck Squamous Cell Carcinoma: A Review From the American Head and Neck Society.

Importance: While neoadjuvant chemotherapy for head and neck squamous cell carcinoma dates to the earliest multidisciplinary approaches, the introduction of immune checkpoint inhibitors (ICIs) has renewed enthusiasm and research into its use. Although neoadjuvant therapy has remained mostly investigative through single-institutional clinical trials for mucosal head and neck squamous cell carcinoma, new data have emerged to support its use.

Observations: A narrative review was conducted by the American Head and Neck Society to address current literature, evolving research, and gaps in knowledge surrounding neoadjuvant therapy.

Current Progress and Future Directions of Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Narrative Review.

Importance: For decades, the 3 therapeutic pillars for head and neck squamous cell carcinoma (HNSCC) have been radiation therapy, chemotherapy, and surgery. In recent years, a fourth pillar, immunotherapy, has shifted the existing paradigm of oncologic care by improving survival outcomes. This narrative review highlights key completed and ongoing clinical trials that have led to new therapeutic approaches and are aiming to further alter the current standard of care.

First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer.

Background: Cytokine induced memory-like natural killer (CIML NK) cells combined with an IL-15 super-agonist (N-803) are a novel modality to treat relapsed/refractory head and neck cancer.

Methods: We report data from a phase I trial of haploidentical CIML NK cells combined with N-803 with or without ipilimumab (IPI) in relapsed/refractory head and neck cancer patients after a median of 6 prior lines of therapy. The trial adhered to a 3 + 3 dose de-escalation design, with primary endpoint being safety.

A Prospective Trial of Biomarker-Guided Surveillance for HPV-Positive Oropharynx Cancer Using Plasma Tumor Tissue-Modified Viral HPV DNA.

Purpose: Observational studies suggest circulating tumor human papillomavirus (HPV) DNA may facilitate early detection of recurrent HPV-positive oropharynx cancer. We prospectively investigated whether biomarker-guided surveillance detects recurrence earlier than the standard-of-care methods.

Patients And Methods: We enrolled patients evaluated for HPV-positive oropharynx cancer at a single center from November, 2020, to April, 2023, undergoing curative-intent treatment in a single-arm cohort study.

T cell dynamics with neoadjuvant immunotherapy in head and neck cancer.

Immune-checkpoint inhibitors (ICIs) are being tested as neoadjuvant therapies in various solid tumours, including in patients with head and neck squamous cell carcinoma (HNSCC), with promising results. Key findings thus far include that this approach is well-tolerated with favourable clinical outcomes including promising pathological response rates in initial studies. Pathological responses are likely to be increased by combining other agents with anti-PD-(L)1 antibodies.

Personalized ctDNA for Monitoring Disease Status in Head and Neck Squamous Cell Carcinoma.

Purpose: Many patients with locoregionally advanced human papillomavirus-negative head and neck squamous cell carcinoma (HNSCC) relapse. ctDNA has the potential to identify minimal residual disease, but its clinical utility for virus-negative HNSCC is not well understood.

Experimental Design: We retrospectively evaluated a personalized, commercial ctDNA assay (Signatera, Natera) during clinical care of patients treated for predominantly newly diagnosed human papillomavirus-negative HNSCC.

Perspectives on Referral Pathways for Timely Head and Neck Cancer Care.

Importance: Timely diagnosis and treatment are of paramount importance for patients with head and neck cancer (HNC) because delays are associated with reduced survival rates and increased recurrence risk. Prompt referral to HNC specialists is crucial for the timeliness of care, yet the factors that affect the referral and triage pathway remain relatively unexplored. Therefore, to identify barriers and facilitators of timely care, it is important to understand the complex journey that patients undertake from the onset of HNC symptoms to referral for diagnosis and treatment.

Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas.

Unlabelled: The MUC1-C protein is aberrantly expressed in adenocarcinomas of epithelial barrier tissues and contributes to their progression. Less is known about involvement of MUC1-C in the pathogenesis of squamous cell carcinomas (SCC). Here, we report that the MUC1 gene is upregulated in advanced head and neck SCCs (HNSCC).

Enhanced oral versus flank lymph node T cell response parallels anti-PD1 efficacy in head and neck cancer.

Objectives: Understanding head and neck tissue specific immune responses is important for elucidating immunotherapy resistance mechanisms to head and neck squamous cell carcinoma (HNSCC). In this study, we aimed to investigate HNSCC-specific immune response differences between oral and subcutaneous flank tumor transplantation in preclinical models.

Materials And Methods: The MOC1 syngeneic mouse oral carcinoma cell line or versions expressing either the H2Kb-restricted SIINFEKL peptide from ovalbumin (MOC1OVA) or ZsGreen (MOC1ZsGreen) were inoculated into mouse oral mucosa (buccal space) or subcutaneous flank and compared for immune cell kinetics in tumors and tumor-draining lymph nodes (TDLNs) and for anti-PD1 response.

Patient Experience of Head and Neck Surgery With Free Flap Reconstruction.

Importance: Major head and neck surgery with microvascular free tissue transfer reconstruction is complex, with considerable risk of morbidity. Little is known about patients' experiences, including decision-making prior to, and regret following, free flap surgery.

Objective: To characterize patient experiences and decision regret of patients undergoing head and neck reconstructive free flap surgery.

Targeting Dendritic Cell Dysfunction to Circumvent Anti-PD1 Resistance in Head and Neck Cancer.

Purpose: Neoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed.

Experimental Design: We integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance.

TREX1 Inactivation Unleashes Cancer Cell STING-Interferon Signaling and Promotes Antitumor Immunity.

Unlabelled: A substantial fraction of cancers evade immune detection by silencing Stimulator of Interferon Genes (STING)-Interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic, or DNA-damaging therapies can restore antitumor immunity in multiple preclinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA.

Personal Social Networks and Care-Seeking for Head and Neck Cancer: A Qualitative Study.

Objectives: To investigate the role of patients' personal social networks (SNs) in accessing head and neck cancer (HNC) care through patients' and health care workers' (HCWs) perspectives.

Study Design: Qualitative study.

Setting: Tertiary HNC centers at 2 academic medical centers, including 1 safety net hospital.

Circulating tumor-tissue modified HPV DNA testing in the clinical evaluation of patients at risk for HPV-positive oropharynx cancer: The IDEA-HPV study.

Objectives: While survival outcomes are favorable for Human Papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (OPSCCs), early diagnosis may minimize treatment-related morbidity and mortality. This study evaluated circulating tumor tissue-modified viral (TTMV)-HPV DNA plasma testing to facilitate early diagnosis of HPV-positive OPSCCs.

Methods: In this prospective exploratory cohort study, patients presenting to an Otolaryngology-Head and Neck Surgery clinic with unexplained signs or symptoms considered high-risk for HPV-positive OPSCC were recruited between March 2021-October 2022.

Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti-PD-1 in head and neck cancer.

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti-programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking.

SMYD3 represses tumor-intrinsic interferon response in HPV-negative squamous cell carcinoma of the head and neck.

Cancers often display immune escape, but the mechanisms are incompletely understood. Herein, we identify SMYD3 as a mediator of immune escape in human papilloma virus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an aggressive disease with poor response to immunotherapy with pembrolizumab. SMYD3 depletion induces upregulation of multiple type I interferon (IFN) response and antigen presentation machinery genes in HNSCC cells.