Publications by authors named "Joseph Califano"

Background: Limited understanding of the biology predisposing certain human papillomavirus-related (HPV+) oropharyngeal squamous cell carcinomas (OPSCCs) to relapse impedes therapeutic personalization. We aimed to identify molecular traits that distinguish recurrence-prone tumors.

Methods: 50 HPV+ OPSCCs that later recurred (cases) and 50 non-recurrent controls matched for stage, therapy, and smoking history were RNA-sequenced.

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Objective: To further characterize the clinicopathologic features of oral verrucous carcinoma.

Methods: In accordance with PRISMA guidelines, a systematic review of the Medline, Web of Science, Embase, and Cochrane databases was performed in search of articles evaluating clinicopathologic features of oral verrucous carcinoma. Primary outcomes of interest included tumor subsites, T-staging, rates of cervical lymph node metastases, rates of distant metastases, 5-year survival (overall, disease-free, or disease-specific), and recurrence rates.

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Article Synopsis
  • Extrachromosomal circular DNA (ecDNA) is commonly found in various human cancers, particularly in oropharyngeal cancer linked to the human papillomavirus (HPV), but its role in cancer development is not fully understood.
  • Researchers studied the epigenetic characteristics of hybrid ecDNA in HPV-positive oropharyngeal cancer cell lines and tumor models, discovering that HPV oncogenes E6/E7 are associated with unique enhancer regions.
  • By using targeted therapies, such as CRISPR interference and specific inhibitors, they were able to decrease E6/E7 gene expression and inhibit tumor growth, highlighting the potential for new treatments that target ecDNA-driven cancer biology.
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Importance: Oral and oropharyngeal cancer have low survival rates, and incidence continues to increase.

Objective: To determine whether soluble CD44 and total protein (TP) are useful for monitoring head and neck cancer recurrence, either used in a point-of-care (POC) test or as individual laboratory-based biomarkers.

Design, Setting, And Participants: This multi-institutional nonrandomized clinical trial testing a novel diagnostic/screening assay took place across the University of California, San Diego; Johns Hopkins University; the Greater Baltimore Medical Center; New York University; and the San Diego Veterans Affairs Hospital.

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Purpose: Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is a distinct disease from other head and neck tumors. This guideline provides evidence-based recommendations on the critical decisions in its curative treatment, including both definitive and postoperative radiation therapy (RT) management.

Methods: ASTRO convened a task force to address 5 key questions on the use of RT for management of HPV-associated OPSCC.

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Rationale And Objective: Treatment for head and neck cancer (HNC) can lead to decreased oral intake which often requires gastrostomy tube (g-tube) placement to provide nutritional support. A multidisciplinary team (MDT) consisting of interventional radiology (IR), HNC oncology and surgery, nutrition, and speech language pathology departments implemented an expedited outpatient g-tube placement pathway to reduce hospital stays and associated costs, initiate feeds sooner, and improve communication between care teams. This single center study investigates differences in complications, time to procedure and costs savings with implementing this pathway.

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There are over 220 identified genotypes of Human papillomavirus (HPV), and the HPV genome encodes 3 major oncogenes, E5, E6, and E7. Conservation and divergence in protein sequence and function between low-risk versus high-risk oncogenic HPV genotypes has not been fully characterized. Here, we used modern computational and structural folding algorithms to perform a comparative analysis of HPV E5, E6, and E7 between multiple low risk and high risk genotypes.

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Salivary glands have essential roles in maintaining oral health, mastication, taste and speech, by secreting saliva. Salivary glands are composed of several types of cells, and each cell type is predicted to be involved in the carcinogenesis of different types of cancers including adenoid cystic carcinoma (ACC), acinic cell carcinoma (AciCC), salivary duct carcinoma (SDC), myoepithelial carcinoma (MECA) and other histology. In our study, we performed single nucleus RNA-seq on three human salivary gland samples to clarify the gene expression profile of each complex cellular component of the salivary glands and related these expression patterns to expression found in salivary gland cancers (SGC) to infer cell of origin.

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Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs , however, remains elusive. Here we employ cell tracing approaches with spatiotemporally controlled oncogene activation and tumor suppressor inhibition to unveil the processes underlying oral epithelial progenitor cell reprogramming into cancer stem cells (CSCs) at single cell resolution.

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Article Synopsis
  • HPV-associated oropharynx carcinoma (HPVOPC) tumors exhibit low mutational burden, and studying other alterations like DNA methylation, alternative splicing, and copy number variation can reveal more about how this cancer develops.
  • Research identified that methylation changes had the strongest connection to gene expression networks, notably within G protein-coupled receptor (GPCR) pathways, including immune-related signals from CXCR3 cytokines.
  • In vivo studies showed that blocking the CXCR3 receptor slowed tumor growth in mice lacking an immune response, indicating that while the CXCR3 axis can promote tumor growth, it can also be influenced by the immune system, highlighting the complexity of targeting this pathway in treatment.
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Tumor initiation represents the first step in tumorigenesis during which normal progenitor cells undergo cell fate transition to cancer. Capturing this process as it occurs in vivo, however, remains elusive. Here we employ spatiotemporally controlled oncogene activation and tumor suppressor inhibition together with multiomics to unveil the processes underlying oral epithelial progenitor cell reprogramming into tumor initiating cells (TIC) at single cell resolution.

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Importance: Head and neck squamous cell carcinoma is a highly lethal cancer that is often associated with human papillomavirus (HPV). Recent studies have shown promise in the use of HPV DNA detection in salivary rinses and plasma as a factor associated with a future diagnosis of HPV-positive oropharynx cancer (HPVOPC). However, the use of plasma and salivary HPV DNA detection in defining risk for recurrence in the context of a prospective, phase 3, clinical trial coupled with standardized clinical surveillance has not been reported.

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Objective: To determine variables associated with longer wait times and decreased patient satisfaction. To determine the association of trainees with clinic wait times and patient satisfaction scores in an academic center.

Study Design: Cross-sectional study.

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Objectives: Most transoral robotic surgery (TORS) literature for HPV-positive oropharyngeal squamous cell carcinoma (HPV-OPC) derives from high-volume tertiary-care centers. This study aims to describe long-term recurrence and survival outcomes among Veterans Health Administration patients.

Materials And Methods: Using the US Veterans Affairs database, we identified patients with HPV-OPC treated with TORS between January 2010 and December 2016.

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The role that human papillomavirus (HPV) oncogenes play in suppressing responses to immunotherapy in cancer deserves further investigation. In particular, the effects of HPV E5 remain poorly understood relative to E6 and E7. Here, we demonstrate that HPV E5 is a negative regulator of anti-viral interferon (IFN) response pathways, antigen processing, and antigen presentation.

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Objective: The role and extent of neck dissection in primary parotid cancer are controversial. Herein, we characterize patterns of lymph node metastasis in parotid cancer.

Study Design: Retrospective analysis.

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Bone autografts remain the gold standard for bone grafting surgeries despite having increased donor site morbidity and limited availability. Bone morphogenetic protein-loaded grafts represent another successful commercial alternative. However, the therapeutic use of recombinant growth factors has been associated with significant adverse clinical outcomes.

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Background: HPV-positive oropharyngeal squamous cell carcinomas (OPSCCs) are sensitive to chemo-radiation therapy and have favorable survival outcomes compared with HPV-negative cancers. These tumors are usually not related to tobacco and alcohol exposure. Therefore, diagnosing HPV-positive OPSCCs for the appropriate disease management is crucial, and no suitable markers are available for detecting early malignancies in HPV-infected tissues.

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Purpose: HPV-positive oropharyngeal carcinoma (HPV-OPC) is increasingly treated with primary surgery. The National Comprehensive Cancer Network (NCCN) recommends adjuvant therapy for surgically treated HPV-OPC displaying adverse pathological features (AF). We evaluated adjuvant radiotherapy patterns and outcomes in surgically treated AF-positive HPV-OPC (AF-HPV-OPC).

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Despite the promise of immune checkpoint inhibition (ICI), therapeutic responses remain limited. This raises the possibility that standard of care treatments delivered in concert may compromise the tumor response. To address this, we employ tobacco-signature head and neck squamous cell carcinoma murine models in which we map tumor-draining lymphatics and develop models for regional lymphablation with surgery or radiation.

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Objectives: To compare overall survival outcomes associated with transoral laser microsurgery (TLM) with neck dissection versus definitive radiotherapy in the management of T2N0 supraglottic squamous cell carcinoma.

Methods: Data were extracted from the National Cancer Database concerning patients with cT2N0M0 supraglottic cancer treated with either TLM and neck dissection with minimum lymph node yield of 10 or definitive radiotherapy. Predictors of overall survival were assessed via Cox proportional hazards regression.

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Plant-based, synthetic, and endogenous cannabinoids have been shown to control a diverse array of biological processes, including regulation of cell fate across cancers. Their promise as broad-based antitumor agents in preclinical models has led to the initiation of pilot clinical trials. Session 5 of the National Cancer Institute's Cannabis, Cannabinoids and Cancer Research Symposium provides an overview of this research topic.

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Background: Little is known regarding the rate and clinical outcomes of asymptomatic carriers of SARS-CoV-2 among patients with cancer. Detection of asymptomatic carriers is important in this population given the use of myelosuppressive and immunomodulating therapies. Understanding the asymptomatic carrier rate will help to develop mitigation strategies in this high-risk cohort.

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