Publications by authors named "Mark W Lingen"

Background: Adenoid cystic carcinoma (ACC) is a rare glandular malignancy, commonly originating in salivary glands of the head and neck. Given its protracted growth, ACC is usually diagnosed in advanced stage. Treatment of ACC is limited to surgery and/or adjuvant radiotherapy, which often fails to prevent disease recurrence, and no FDA-approved targeted therapies are currently available.

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Cetuximab induces responses in about 13% of head and neck squamous cell carcinomas (HNSCC). We describe the molecular mechanism of acquired resistance to cetuximab, which could be overcome by switching to a different anti-EGFR antibody. Biopsies were collected at three different time points: before the start of cetuximab (PRE-cetux), at acquired resistance to cetuximab (AR-cetux), and at acquired resistance to duligotuzumab (AR-duligo).

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Importance: Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in curative human papillomavirus-positive oropharyngeal cancer (HPV+ OPC) remains undefined. Neoadjuvant nivolumab and chemotherapy followed by response-adaptive treatment in HPV+ OPC may increase efficacy while reducing toxicity.

Objective: To determine the deep response rate and tolerability of the addition of neoadjuvant nivolumab to chemotherapy followed by response-adapted locoregional therapy (LRT) in patients with HPV+ OPC.

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Article Synopsis
  • A recent study explored the rising incidence of oral tongue cancers in the US since the 1980s, investigating links between inflammatory tongue conditions and various cancers in elderly individuals aged 65 and older.
  • Researchers analyzed data from 200,000 controls and thousands of cancer cases, focusing on conditions like glossitis and oral precancer diagnosed more than 12 months before cancer diagnosis.
  • The study found that patients with tongue cancer had a significantly higher prevalence of inflammatory tongue conditions (6.0% vs. 0.6% in controls), with strong associations for glossitis and other specified conditions, while associations were weaker for other oral cavity and oropharyngeal cancers.
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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.

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Head and neck squamous cell carcinoma (HNSCC) is the world's 6th most common malignancy. Oral cavity SCC (OCSCC) represents approximately one third of the HNSCC cases diagnosed annually in the United States. Despite therapeutic advances, OCSCC is frequently lethal, with a modest 5-year survival.

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Background: The purpose of this systematic review was to examine whether dental intervention involving bone or soft-tissue manipulation preradiotherapy (pre-RT) is associated with lower rates of osteoradionecrosis of the jaw (ORNJ) in patients with head and neck cancer (HNC).

Types Of Studies Reviewed: The authors included relevant studies from MEDLINE, Embase, and Cochrane Library, including observational studies published from 2007 through 2021 and involving adults who underwent dental intervention pre-RT for HNC. Authors assessed evidence certainty by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

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  • Oral cavity squamous cell carcinoma (OCSCC) is challenging to treat, often leading to toxic side effects from conventional chemotherapy like platinum-based drugs.
  • PRV111 is a new nanotechnology that allows for localized delivery of cisplatin to tumors, minimizing systemic exposure and toxicity while enhancing drug retention in the tumor.
  • In animal studies and a clinical trial, PRV111 showed significant effectiveness with a 69% reduction in tumor size in about a week, no serious side effects, and suggests potential for better patient outcomes when combined with existing treatments for OCSCC.
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Background: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC.

Methods: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m in recurrent HNSCC.

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Background: The early detection of oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD), followed by appropriate treatment, may improve survival and reduce the risk for malignant transformation respectively. This is an update of a Cochrane Review first published in 2013.

Objectives: To estimate the diagnostic test accuracy of conventional oral examination, vital rinsing, light-based detection, mouth self-examination, remote screening, and biomarkers, used singly or in combination, for the early detection of OPMD or OSCC in apparently healthy adults.

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Head and neck squamous cell carcinoma (HNSCC) is a molecularly heterogeneous disease, with a 5-year survival rate that still hovers at ~60% despite recent advancements. The advanced stage upon diagnosis, limited success with effective targeted therapy and lack of reliable biomarkers are among the key factors underlying the marginally improved survival rates over the decades. Prevention, early detection and biomarker-driven treatment adaptation are crucial for timely interventions and improved clinical outcomes.

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Immune suppression by CD4FOXP3 regulatory T (Treg) cells and tumor infiltration by CD8 effector T cells represent two major factors impacting response to cancer immunotherapy. Using deconvolution-based transcriptional profiling of human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCCs) and other solid cancers, we demonstrate that the density of Treg cells does not correlate with that of CD8 T cells in many tumors, revealing polarized clusters enriched for either CD8 T cells or CD4 Treg and conventional T cells. In a mouse model of carcinogen-induced OSCC characterized by CD4 T cell enrichment, late-stage Treg cell ablation triggers increased densities of both CD4 and CD8 effector T cells within oral lesions.

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Background: Squamous cell carcinoma is the most common form of malignancy of the oral cavity, and is often proceeded by oral potentially malignant disorders (OPMD). Early detection of oral cavity squamous cell carcinoma (oral cancer) can improve survival rates. The current diagnostic standard of surgical biopsy with histology is painful for patients and involves a delay in order to process the tissue and render a histological diagnosis; other diagnostic tests are available that are less invasive and some are able to provide immediate results.

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The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months).

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Background: Oral cavity squamous cell carcinoma (OCSCC) is the most common head and neck malignancy. Although the survival rate of patients with advanced-stage disease remains approximately 20% to 60%, when detected at an early stage, the survival rate approaches 80%, posing a pressing need for a well validated profiling method to assess patients who have a high risk of developing OCSCC. Tumor DNA detection in saliva may provide a robust biomarker platform that overcomes the limitations of current diagnostic tests.

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The lungs are a common site of metastasis of head and neck (H&N) squamous cell carcinomas (SCC). This study attempts to define p16 immunoexpression and presence of HPV in primary SCC of the lung and determine their usefulness in discriminating between primary lung SCC and metastasis from HPV-associated oropharyngeal primary. Pathology archives were searched for patients with SCC of the lung without SCC elsewhere.

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Article Synopsis
  • Craniofacial osteosarcoma is a rare type of bone cancer, making up only 2-10% of all osteosarcomas, and this study focuses on differentiating it from benign fibro-osseous lesions using specific genetic markers.
  • The research found that MDM2 and CDK4 proteins were expressed in 72.7% of osteosarcoma cases, while all benign lesions tested negative for these markers, suggesting their potential as diagnostic tools.
  • Caution is advised in interpreting positive results since weak MDM2 expression can occur in tumor cells alongside strong expression in associated giant cells, which could complicate the diagnosis.
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  • A study on oral leukoplakia, a common oral precancer, aimed to determine cancer progression risks and the effectiveness of biopsies for predicting outcomes among 4,886 patients at Kaiser Permanente Northern California from 1996 to 2012.* -
  • Results showed a significantly high oral cancer incidence in patients with leukoplakia, indicating biopsied lesions had a notably greater progression risk, but the biopsy decision itself was not very accurate in predicting cancer presence.* -
  • The risk of cancer progression varied with dysplasia levels, with severe dysplasia showing the highest absolute risk (32.2%), while a substantial number of cancers (39.6%) developed from previously biopsied but non-progressive lesions.*
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