Wendell Yarbrough

• Professor
• Chair at University of North Carolina at Chapel Hill

Background: Salivary gland cancer (SGC) comprises a very heterogeneous group of rare neoplasms, accounting for approximately 2% to 6% of head and neck malignancies. Surgery with or without adjuvant radiotherapy is the main treatment regimen. However, patients who are ineligible for surgery, including late-stage, recurrent, or metastatic disease, ha...

Introduction: Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have high risk of disease progression and death after standard concurrent chemoradiotherapy (CCRT). We are conducting a prospective trial to investigate the efficacy of combining immune checkpoint blockade (ICB) with PARP inhibition prior to and following...

Background: Improving understanding of head and neck squamous cell carcinoma (HNSCC) has led to the discovery of novel molecular markers to stratify risk and guide treatment decisions. Recently, we have identified two subtypes of HPV+ OPSCC – one with good prognosis and one with poor prognosis. The subtypes are distinct in many ways – somatic genes...

Background Differences in patient populations and outcomes by hospital type are becoming increasingly relevant as health care systems shift to value-based care models. There is a paucity of literature on patient-level and hospital-level differences for patients with head and neck squamous cell carcinoma (HNSCC). The objective of this study was to e...

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) com...

Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it i...

Objective Compare surgical and swallow outcomes in robotic versus traditional laryngeal cleft (LC) repairs. Study Design Retrospective cohort study. Setting Tertiary care pediatric hospital. Methods Pediatric patients who underwent robotic or traditional (open or endoscopic) LC repair between 2010 and 2021 were identified. Patient characteristic...

Objective While evidence continues to emerge on the negative health effects of electronic cigarettes (e‐cigarettes) on the lungs, little is known regarding their deleterious effects on the upper airway. The purpose of this review is to summarize the toxicological effects of e‐cigarettes, and their components, on the upper airway. Data Sources PubM...

Background In rural states, travel burden for complex cancer care required for head and neck squamous cell carcinoma (HNSCC) may affect patient survival, but its impact is unknown. Methods Patients with HPV‐negative HNSCC were retrospectively identified from a statewide, population‐based study. Euclidian distance from the home address to the treat...

Background Poor oral health has been identified as a prognostic factor potentially affecting the survival of patients with head and neck squamous cell carcinoma. However, evidence to date supporting this association has emanated from studies based on single cohorts with small-to-modest sample sizes. Methods Pooled analysis of 2449 head and neck sq...

Human papillomaviruses (HPV) are associated with both benign and malignant epithelial lesions. High-risk HPV subtype HPV 16 is the causative agent of cervical and the majority of oropharyngeal squamous cell carcinomas. Despite the continuous increase in the disease burden, mechanisms and pathways of HPV16-induced cancer growth are not fully underst...

Within head and neck squamous cell carcinoma (HNSCC), those induced by the human papillomavirus (HPV+) have a more hypermethylated genome compared to those that are negative (HPV-). Therefore, our lab explored the usage of the demethylating agent 5-azacytidine (5-aza), an FDA-approved drug for the treatment of myelodysplasia and acute myeloid leuke...

We analyzed transcriptional data from 104 HPV+ (Human papillomavirus) HNSCC (head and neck squamous cell carcinoma) tumors together with two publicly available sources to identify highly robust transcriptional programs (modules) which could be detected consistently despite heterogeneous sequencing and quantification methodologies. Among 22 modules...

Background Patients with locally advanced head and neck squamous cell cancer (HNSCC) are treated with surgery followed by adjuvant (chemo) radiotherapy or definitive chemoradiation, but recurrence rates are high. Immune checkpoint blockade improves survival in patients with recurrent/metastatic HNSCC; however, the role of chemo‐immunotherapy in the...

Papillomaviruses are species specific, non-enveloped, double-stranded DNA viruses that have an ~8kb circular genome enclosed by a 55 nm icosahedral capsid. Human papillomaviruses (HPV) are associated with both benign and malignant epithelial lesions. High-risk HPV subtypes are the causative agents of cervical and the majority of oropharyngeal squam...

The incidence of HPV-positive head and neck squamous cell carcinoma (HNSCC) is now being considered an epidemic in the US and Western Europe as rates have surpassed those for cervical cancer. For approximately 14,400 patients per year in the US, initial therapy is aggressive and often results in adverse lifelong side effects such as difficulty swal...

Incidence of human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) has dramatically increased in the U.S. surpassing cervical cancer since 2012. Among HNSCC, HPV+ HNSCC patients have a favorable prognosis; however, approximately 20-30% suffer recurrence. Given the morbidity of current therapy, therapeutic de-escalation...

Background Head and neck squamous cell cancer (HNC) occurs at higher rates among people with HIV (PWH). This study compares the impact of sociodemographic and clinicopathologic characteristics on outcomes among PWH-HNSCC compared to Uninfected- HNSCC patients. Methods Patient data from individuals with HNSCC were collected at a single academic hos...

Purpose/Objective(s) Accurate diagnosis of human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC) affects prognosis and can alter the treatment plan. We evaluated the diagnostic accuracy of FNA biopsies to determine malignancy and HPV status in OPSCC at our institution. Methods Pathology samples from consecutive patient...

[This corrects the article DOI: 10.1016/j.isci.2022.105077.].

Squamous cell carcinoma of the oropharynx caused by HPV type 16 (HPV16+ OPSCC) is the most common HPV-associated malignancy in the USA and has many molecular differences from uterine cervical squamous cell carcinoma (UCSCC). Our understanding of HPV oncogenesis relied on studies of UCSCC revealing a consensus model reliant on HPV integration with a...

This diagnostic study describes the development of an assay for human papillomavirus–driven cancers of the oropharynx and the role viral integration could play in the process.

APOBEC3 family members are cytidine deaminases catalyzing conversion of cytidine to uracil. Many studies have established a link between APOBEC3 expression and cancer development and progression, especially APOBEC3A (A3A) and APOBEC3B(A3B). Preclinical studies with human papilloma-virus positive (HPV+) head and neck squamous cell carcinoma (HNSCC)...

Over 70% of oropharyngeal head and neck squamous cell carcinoma (HNSC) cases in the United States are positive for human papillomavirus (HPV) yet biomarkers for stratifying oropharyngeal HNSC patient risk are limited. We used immunogenomics to identify differentially expressed genes in immune cells of HPV(+) and HPV(−) squamous carcinomas. Candidat...

Human papillomavirus–positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV-associated malignancy in the United States and is primarily caused by HPV subtype 16 (HPV16). Favorable treatment outcomes have led to increasing interest in treatment deescalation to reduce treatment-related morbidity. Prognostic biomar...

Human papillomavirus (HPV) causes approximately 80% of head and neck squamous cell carcinoma (HNSCC) in the oropharynx, and its incidence is now higher than uterine cervical cancer in the US. The CDC estimates that this common sexually transmitted disease accounts for nearly 13,000 HPV+ HNSCC patients per year in the United States. Despite having a...

Evolving understanding of head and neck squamous cell carcinoma (HNSCC) is leading to more specific diagnostic disease classifications. Among HNSCC caused by the human papilloma virus (HPV), tumors harboring defects in TRAF3 or CYLD are associated with improved clinical outcomes and maintenance of episomal HPV. TRAF3 and CYLD are negative regulator...

Purpose/Objective(s) We hypothesized that molecular characteristics of HPV-associated head and neck squamous cell carcinoma (HPV+ HNSCC) will predict tumor behavior and response to therapy. Using TCGA, we previously correlated genetic defects in NF-kB regulators with outcome. Here, we validate this prognostic biomarker and identify a gene expressio...

Purpose/Objective(s) HPV-positive squamous cell carcinoma of the oropharynx (HPV+ OPSCC) is the most prevalent HPV-associated malignancy in the United States and is primarily caused by HPV16. Favorable treatment outcomes have led to increasing interest in treatment de-escalation to reduce treatment-related morbidity. Prognostic biomarkers are neede...

Purpose To assess the prevalence and predictors of mental health disorders (MDHs) among head and neck squamous cell carcinoma (HNSCC) survivors, and the association with health-related quality of life (HRQOL), pain, and survival outcomes. Materials and methods This was a retrospective, cross-sectional study of HNSCC survivors surveyed at an outpat...

Background: Little is known about how factors combine to influence progression of squamous cell carcinoma of the head and neck (HNSCC). We aimed to evaluate multidimensional influences of factors associated with HNSCC stage by race. Methods: Using retrospective data, patients with similar socioeconomic status (SES), access to care (travel time/d...

Objective To examine the prevalence and predictors of patient-reported barriers to care among survivors of head and neck squamous cell carcinoma and the association with health-related quality of life (HRQOL) outcomes. Study Design Retrospective cohort study. Setting Outpatient oncology clinic at an academic tertiary care center. Methods Data we...

Introduction Olfactory neuroblastoma (ONB) is a rare cancer of the sinonasal region. We provide a comprehensive analysis of this malignancy with molecular and clinical trial data on a subset of our cohort to report on the potential efficacy of somatostatin receptor 2 (SSTR2)-targeting imaging and therapy. Methods We conducted a retrospective analy...

Background There is a paucity of data on financial toxicity among patients with head and neck squamous cell carcinoma (HNSCC). Materials This was a retrospective, cross-sectional study of patients with HNSCC surveyed at an outpatient oncology clinic. Results The sample included 202 patients with HNSCC with a mean age of 59.6 years (SD 10.0). Ther...

Background NUT carcinoma is an aggressive malignancy characterized by translocations in the NUTM1 gene. There are currently no consensus treatment recommendations for NUT carcinomas. Methods Here, we describe the case of a previously healthy male diagnosed with NUT carcinoma after presenting with sinus pressure, found to have a sinonasal mass and...

Objectives/Hypothesis The current state of the U.S. public's knowledge of the relationship between human papillomavirus (HPV) and HPV vaccinations to oropharyngeal squamous cell carcinoma (OPSCC) is unknown. Our objective was to 1) assess the general population's knowledge of human papillomavirus (HPV) and willingness to vaccinate, and 2) assess wh...

Objective To estimate the relative prognostic ability of socioeconomic status (SES) compared to overall stage for HPV-negative head and neck squamous cell carcinoma (HNSCC) Materials and methods Data were obtained from the Carolina Head and Neck Cancer Epidemiology Study (CHANCE). An empirical 4-category SES classification system was created. Cox...

Introduction: Incidence of non-AIDS-defining cancers, including head and neck cancer (HNC), is rising among people living with HIV (PLWH). This study compares outcomes of HIV+ and Uninfected HNC patients at a single institution. Methods: Yale Tumor Registry query identified 3,488 HNC patients, including 50 with HIV, for analysis (Clinical Cohort, 2...

Objective To assess knowledge regarding head and neck cancers (HNCs) in 2020, factors associated with knowledge of the role of human papillomavirus (HPV) in HNCs, and factors associated with exposure to Oral, Head and Neck Cancer Awareness Week (OHANCAW). Study Design Cross-sectional survey. Setting Online. Methods The survey was distributed to...

Background Human papillomavirus–positive (HPV+) squamous cell carcinoma of the oropharynx (OPSCC) is the most prevalent HPV‐associated malignancy in the United States. Favorable treatment outcomes have led to increased interest in treatment de‐escalation to reduce treatment morbidity as well as the development of prognostic markers to identify appr...

Objective: The objective of this study was to evaluate the clinical outcomes in a cohort of patients with early-stage oral tongue squamous cell carcinoma (OTSCC). Materials and methods: We conducted a retrospective analysis of patients with pT1-T2N0 (American Joint Committee on Cancer [AJCC] seventh edition) OTSCC treated from 2000 to 2018. Two-...

Simple Summary High levels of global genome methylation in HPV-associated head and neck cancer prompted us to explore demethylation as a potential treatment by determining mechanisms of its toxicity in HPV-positive head and neck cancer cells. Previously, we reported that demethylating drug 5-azaC stabilizes p53 and reduces the expression of HPV gen...

Objectives/Hypothesis To determine drivers of the racial disparity in stage at diagnosis and overall survival (OS) between black and white patients with HPV‐negative head and neck squamous cell carcinoma (HNSCC). Study Design Retrospective cohort study. Methods Data were examined from of a population‐based HNSCC study in North Carolina. Multivari...

The incidence of oral tongue squamous cell carcinoma has been increasing in young patients (≤45 years) without a clear etiologic driver. It is unknown if younger patients have an increased risk of recurrence compared to older patients. A literature search was conducted through January 2020 using PubMed/MEDLINE, Embase, Cochrane, Scopus, Science Dir...

Background Decreased access to preventive care services has been proposed as a mechanism for the association between low socioeconomic status (SES) and advanced stage at diagnosis in patients with head and neck squamous cell carcinoma (HNSCC). Methods Retrospective analysis of patients diagnosed with HNSCC in North Carolina between 2002 and 2006....

Background There is a well documented racial disparity in overall survival for oropharyngeal squamous cell carcinoma (OPSCC); however, it is unknown to what extent this disparity varies by HPV‐status. Methods A literature search was conducted through December 2019 using Ovid Medline, Cochrane Library, Embase, Scopus, and Clinicaltrials.gov. PRISMA...

p> Introduction: The presence of the t(11;19) chromosomal translocation and its CRTC1-MAML2 (C1/M2) fusion product occurs frequently in salivary mucoepidermoid carcinoma (MEC) and has been correlated with a favorable prognosis. Recently, whole-exome sequencing studies found genomic alterations in MEC to be infrequent, which supports the role of C1/...

Abstract Recent advancements in computational power, machine learning, and artificial intelligence technology have enabled automated evaluation of medical images to generate quantitative diagnostic and prognostic biomarkers. Such objective biomarkers are readily available and have the potential to improve personalized treatment, precision medicine,...

PURPOSE Plasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence. METHOD...

Background: EBRT in resected, nonmetastatic anaplastic thyroid cancer (ATC) remains undefined. We evaluated patterns/outcomes with EBRT and chemotherapy in this setting. Methods: This retrospective analysis included patients identified from the National Cancer Database with nonmetastatic ATC from 2004 to 2014 who underwent non-palliative resecti...

PURPOSE Extranodal extension (ENE) is a well-established poor prognosticator and an indication for adjuvant treatment escalation in patients with head and neck squamous cell carcinoma (HNSCC). Identification of ENE on pretreatment imaging represents a diagnostic challenge that limits its clinical utility. We previously developed a deep learning alg...

Proliferating tricholemmal tumors (PTTs) are rare benign neoplasms that arise from the outer sheath of a hair follicle. Occasionally, these PTTs undergo malignant transformation to become malignant proliferating tricholemmal tumors (MPTTs). Little is known about the molecular alterations, malignant progression, and management of MPTTs. Here, we des...

PIK3CA is the most frequently mutated gene in HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Prognostic implications of such mutations remain unknown. We sought to elucidate the clinical significance of PIK3CA mutations in HPV-associated OPSCC patients treated with definitive chemoradiation (CRT). Seventy-seven patients with HPV-asso...

Background Concurrent bolus cisplatin with radiation therapy (XRT) is a standard of care for the treatment of LA-HNSCC. Contraindications such as hearing loss, tinnitus, renal dysfunction or neuropathy are common. Radiation elicits and promotes tumor-directed immune-stimulation, which may potentiate anti-PD-1 therapy. Methods This single arm, mult...

Background/aim: This study aimed to evaluate the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) who underwent resection and refused the recommended adjuvant therapy. Patients and methods: Locoregional recurrence-free survival (LRRFS) and time to progression (TTP) were assessed in HNSCC patients treated with surgery who d...

On December 18, 2018, the US Surgeon General declared e-cigarette vaping among adolescents an “epidemic.”¹ This declaration coincided with a report in The New England Journal of Medicine² highlighting a 10% increase in youth vaping between 2017 and 2018, the equivalent of an additional estimated 1.3 million teenagers. In a public hearing in January...

Purpose: To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Materials and methods: Major inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N...

Background: Compared to HPV-negative head and neck squamous cell carcinomas (HNSCCs), HPV-positive HNSCCs are associated with a favorable prognosis in part due to their improved treatment sensitivity. Inactivating mutations in NSD1 were shown to be a favorable prognostic biomarker in laryngeal cancers. Here, we characterize NSD1 mutations from the...

6011 Background: PIK3CA is the most frequently mutated gene in HPV-associated oropharyngeal SCC (OPSCC), with a prevalence of 20-30%. While PIK3CA mutations have been associated with adverse outcomes in cervical cancer, their prognostic significance in HPV-associated OPSCC remains unknown. We sought to elucidate the significance of PIK3CA mutations...

6022 Background: To report the mature results from a prospective phase II clinical trial of highly de-intensified chemoradiotherapy (CRT) for patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods: The major inclusion criteria were: 1) T0-T3, N0-N2, M0, 2) p16 positive, and 3) minimal/remote smoking history. Treatment w...

Recent studies have revealed the mutational signatures underlying the somatic evolution of cancer, and the prevalences of associated somatic genetic variants. Here we estimate the intensity of positive selection that drives mutations to high frequency in tumors, yielding higher prevalences than expected on the basis of mutation and neutral drift al...

TPS73 Background: When surgery is used as the primary therapeutic modality for locally-advanced HNSCC, radiation therapy (XRT) is frequently recommended post-operatively due to high rates of recurrence. In high-risk patients; i.e., those with positive surgical margins or extra-nodal extension (ENE) on surgical pathology, the addition of chemotherap...

Purpose: Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in TP53, resulting in treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed and an oncogeni...

Understanding of oropharyngeal squamous cell carcinoma has significantly progressed over the last decades, and the concept that this disease can be subdivided into two distinct entities based on human papilloma virus (HPV) status has gained acceptance. To combat the constantly growing epidemic of HPV+ oropharyngeal cancer, further investigation and...

Objectives To compare long‐term oncologic outcomes and adjuvant therapies for patients treated with transoral robotic surgery (TORS), nonrobotic surgery, or transoral laser microsurgery (TLM). Study Design A retrospective analysis of the National Cancer Database (2010–2014). Methods Patients with clinical tumor (T)1 and T2 oropharyngeal squamous...

Purpose/Objective(s) Initial de-escalation studies for HPV-associated oropharyngeal squamous cell carcinomas (HPV-A OPC) altered radiation therapy dose or the systemic agent used. Newer trials examine the disease control achieved with a decreased elective nodal field. We examined patterns of nodal involvement in patients with HPV-A OPC with a focus...

Cell lines are important tools for biological and preclinical investigation, and establishing their relationship to genomic alterations in tumors could accelerate functional and therapeutic discoveries. We conducted integrated analyses of genomic and transcriptomic profiles of 15 human papillomavirus (HPV)-negative and 11 HPV-positive head and neck...

Identification of nodal metastasis and tumor extranodal extension (ENE) is crucial for head and neck cancer management, but currently only can be diagnosed via postoperative pathology. Pretreatment, radiographic identification of ENE, in particular, has proven extremely difficult for clinicians, but would be greatly influential in guiding patient m...

Objectives: Approximately 3% to 9% of head and neck cancer presents with a metastatic node and no identifiable primary tumor. These cases of head and neck carcinoma of unknown primary (HNCUP) present a therapeutic challenge. Therapy of this disease varies based on factors such as institutional, surgeon, and patient preference. Evidence demonstrati...

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3) proteins are a family of cytidine deaminases that play important roles in diverse physiological processes in humans. APOBEC3-driven cytidine deamination results in a C-to-U conversion in target nucleotides, classifying this biological activity as a DNA-/RNA-editing mechanis...

Objective Salivary squamous cell carcinomas (SCCs) represent a unique disease entity because many are thought to represent metastases from primary cutaneous malignancies. Nevertheless, they represent a significant proportion of parotid gland cancers and have a notably poor prognosis. Recently, there has been controversy regarding the utility of adj...

Objective: To design and implement a postoperative clinical care pathway designed to reduce intensive care usage on length of stay, readmission rates, and surgical complications in head and neck free flap patients. Methods: A postoperative clinical care pathway detailing timelines for patient care was developed by a multispecialty team. In total...

Objective To characterize treatment delays in surgically treated oropharyngeal cancer, identify factors associated with delays, and associate delays with survival. Study Design Retrospective cross-sectional analysis. Setting Commission on Cancer–accredited institutions. Subjects and Methods We identified patients in the National Cancer Database...

Background Extracapsular extension (ECE) is a well-established prognostic feature in squamous cell cancers of the head and neck. Although some extrapolate data from mucosal head and neck cancer to include ECE as a high-risk feature in salivary gland cancers, data is lacking about ECE’s prognostic value for these malignancies. We investigate whether...

Objective: To characterize treatment delays in oropharyngeal cancer treated with radiation in a national sample, identify factors associated with delays, and associate treatment delays with survival. Materials and methods: We included adults in the National Cancer Database treated for oropharyngeal cancer with primary radiation or chemoradiation...

Objectives To examine the level of awareness of the link between human papillomavirus (HPV) and oropharyngeal cancer (OPC) and epidemiological trends in HPV-related OPC among general practitioners (GPs) in the UK. Design Cross-sectional survey. Participants 384 GPs from England, Scotland, Wales and Northern Ireland. Setting The survey was admini...

Human cancer cell lines have been important tools for biological and preclinical investigation, and establishing their relationship to genomic alterations and subtypes found in tumors could further accelerate functional and therapeutic discoveries. We conducted an integrated analysis of the genomic and transcriptomic profiles of 15 human papillomav...

Background: As the incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) continues to rise, mechanistic knowledge of HPV16-driven HNSCC remains incomplete. HPV(+) and HPV(-) HNSCCs are molecularly distinct, with altered signaling pathways that have been characterized by proteomic technologies. We recently rep...