Head And Neck Cancer Squamous Cell Carcinoma Research Articles

Socioeconomic deprivation correlates with incomplete radiotherapy treatment in head and neck cancer.

There is a high burden of socioeconomic deprivation across Merseyside and, along with this, poorer cancer outcomes. The incidence of head and neck cancer squamous cell carcinoma (HNSCC) within this region is higher than the national average and there are often additional complexities to individual treatment pathways such as poor health literacy, lack of social support and transport options which can impact on adherence to prescribed treatments. AimThis work aims to understand the impact of deprivation on patients diagnosed with HNSCC undergoing chemoradiotherapy (CRT) or radiotherapy (RT) treatment through identifying barriers to adherence. MethodsPatients with HNSCC treated between June 2022-June 2023 were included and data collected through retrospective case note review. Approval was obtained from relevant NHS institution audit departments. Key examined variables were indices of multiple deprivation (IMD), unplanned admission rate, hospital transport use, social support network and provision of additional adhoc appointments during treatment courses. All were correlated with missed radiotherapy appointments. ResultsOut of 359 evaluable patients there were high levels of unplanned appointments with health professionals during CRT/RT (71% of those receiving CRT and 55% of those having RT). 11% (n=39) missed at least one radiotherapy appointment with the commonest reason being unplanned admission to hospital. Despite missed appointments, 25/39 patients completed treatment within prescribed window due to effective RT compensation strategies. On multivariate analysis, unplanned admission, hospital provided transport and crime deprivation quintiles (p=<0.001, p=0.007 and p=0.027 respectively) were found to significantly increase the chance of missed radiotherapy treatment appointments. ConclusionHigh levels of unplanned encounters with health care professionals are encouraging adherence to non-surgical HNSCC treatments. Formalising these adhoc appointments will provide an equitable, robust service. Undertaking hospital transport increases potential for missed treatment appointments. Gaining insight into patient experiences and investing in improved transport services are essential for maximising adherence.

Beyond the initial diagnosis: Epidemiological factors associated with second primary cancers among patients with head and neck squamous cell carcinoma (a SEER-based study).

6081 Background: Patients with Head and Neck cancer squamous cell carcinoma (HNSSC) have an increased risk of developing a Second Primary Cancer (SPC). We evaluated the epidemiological factors associated with SPC among patients with Stage 1-4 HNSCC using the SEER database from 2004-2020. Methods: Stage 1-4 HNSSC cases from 2004-2020, with a minimum of six months of follow-up, were identified using SEER.Stat 8.4.2 using ICD-10 CM codes. Adjusted odd’s ratios (aOR) for developing SPC (dependent variable) and the independent variables (sex, age, race and ethnicity, site of primary cancer, and marital status) were generated using multivariate logistic regression. All the analyses were performed on SAS OnDemand. Results: 127,919 cases of HNSCC were identified from 2004-2020. Oral cavity cancer accounted for 41.2% of the cases. 18,192 (14.2%) patients developed SPC. Patients with primary hypopharynx, laryngeal, and oral cavity cancer had the highest odds of developing SPC (p&lt; 0.0001). The most prevalent sites for developing SPC were the lung (25.0%), head and neck (24.1%), and prostate (10.6 %). Males had significantly higher odds of developing SPC than females (aOR - 1.11 (1.07, 1.5)). When compared to the NH-white population, Hispanics and NH-Asian had significantly lower odds of developing SPC (aOR - 0.72 (0.68, 0.77) and 0.72 (0.68, 0.78) respectively), while NH-Blacks had higher odds of developing SPC (aOR - 1.1(1.01,1.23)). Conclusions: Our study emphasizes the substantial risk of SPC in HNSCC patients, with oral cavity cancer as the predominant primary cancer subtype. Specific HNSCC sites show elevated SPC odds, mainly primary hypopharyngeal cancer, emphasizing the need for targeted surveillance. Demographic variations reveal gender and racial disparities in SPC susceptibility, advocating for tailored monitoring and preventive strategies in high-risk subpopulations to enhance overall cancer care and survivorship. [Table: see text]

855MO Adjuvant immunotherapy after salvage surgery in head and neck cancer squamous cell carcinoma (HNSCC): Phase II trial evaluating the efficacy and the toxicity of Nivolumab (ADJORL1)

855MO Adjuvant immunotherapy after salvage surgery in head and neck cancer squamous cell carcinoma (HNSCC): Phase II trial evaluating the efficacy and the toxicity of Nivolumab (ADJORL1)

Current Insights and Progress in the Clinical Management of Head and Neck Cancer.

Head and neck cancer (HNC), also known as the cancer that can affect the structures between the dura mater and the pleura, is the 6th most common type of cancer. This heterogeneous group of malignancies is usually treated with a combination of surgery and radio- and chemotherapy, depending on if the disease is localized or at an advanced stage. However, most HNC patients are diagnosed at an advanced stage, resulting in the death of half of these patients. Thus, the prognosis of advanced or recurrent/metastatic HNC, especially HNC squamous cell carcinoma (HNSCC), is notably poorer than the prognosis of patients diagnosed with localized HNC. This review explores the epidemiology and etiologic factors of HNC, the histopathology of this heterogeneous cancer, and the diagnosis methods and treatment approaches currently available. Moreover, special interest is given to the novel therapies used to treat HNC subtypes with worse prognosis, exploring immunotherapies and targeted/multi-targeted drugs undergoing clinical trials, as well as light-based therapies (i.e., photodynamic and photothermal therapies).

Perioperative antimicrobial prophylaxis in clean-contaminated head and neck squamous cell cancer surgeries: Is less better?

Judicious use of antibiotics and stringent adherence to practice guidelines is the need of the hour as antibiotic resistance is a rampant problem. Despite several reports in the literature describing the optimal duration of antibiotics, there is no consensus. A "one for all" protocol may be impractical and hence the guidelines need to be tweaked to take into consideration local factors. We designed a protocol for prophylactic antibiotics in clean-contaminated head and neck cancer squamous cell carcinoma (HNSCC) surgeries to prevent unchecked abuse and evaluated its feasibility. Two hundred consecutive patients who underwent a clean-contaminated surgery for HNSCC between January 2017 and December 2019 were included. Single-dose intravenous amoxicillin-clavulanate at induction followed by three doses of amoxicillin-clavulanate, metronidazole, and amikacin in the postoperative period was used. Adherence to the antibiotic protocol was assessed from a prospectively maintained database. The mean age was 55.99 ± 11.71 years. The protocol was effective in 70% of the patients with an acceptable surgical site infection (SSI) rate of 12%. Flap-related complications (9.5%) and oro-cutaneous fistula (5%) were common causes of prolonged antibiotics. On univariate analysis, blood transfusion (P = .014), clinical stage at presentation (P = .028), patients undergoing reconstruction (P = .001), longer operative time (P = .009), and pathological T stage (P = 0.03) were at higher chance of deviating from the protocol. On multivariate analysis, age more than 50 years (OR: 2.14, 95% CI: (1.01, 4.52); P value = 0.047) and reconstruction (OR: 3.36, 95% CI: (1.21, 9.32); P value = 0.020) were found to be significant. A three-dose perioperative antibiotic prophylaxis in clean-contaminated HNSCC surgeries is feasible. Similar protocols should be developed and validated at other major centers to limit the unnecessary use of antibiotics and prevent the emergence of antibiotic resistance.

Metformin increases natural killer cell functions in head and neck squamous cell carcinoma through CXCL1 inhibition

BackgroundMetformin slows tumor growth and progression in vitro, and in combination with chemoradiotherapy, resulted in high overall survival in patients with head and neck cancer squamous cell carcinoma (HNSCC) in...

Risk and incidence of head and neck cancers in veterans living with HIV and matched HIV-negative veterans.

Persons living with HIV/AIDS have a higher incidence of virus-related and tobacco/alcohol-related cancers. This study is the first to estimate the effect of HIV versus HIV-negative veterans on the risk of head and neck squamous cell carcinoma incidence in a large retrospective cohort study. The authors constructed a retrospective cohort study using patient data from 1999 to 2016 from the National Veterans Administration Corporate Data Warehouse and the VA Central Cancer Registry. This cohort study included 45,052 veterans living with HIV/AIDS and 162,486 HIV-negative patients matched by age, sex, and index visit (i.e., HIV diagnosis date or clinic visit date). The age-standardized incidence rates and estimated adjusted hazard ratios were calculated with a Cox proportional hazards regression for oropharyngeal and nonoropharyngeal head and neck cancer squamous cell carcinoma (HNSCC). The authors also abstracted human papillomavirus (HPV) status from oropharyngeal HNSCC diagnosed after 2010. Veterans living with HIV/AIDS (VLWH) have 1.71 (95% confidence interval [CI], 1.36, 2.14) times the risk of oropharyngeal cancer and 2.06 (95% CI, 1.76, 2.42) times the hazard of nonoropharyngeal cancer compared with HIV-negative veterans. VLWH with oropharyngeal squamous cell carcinoma (OPSCC) were more likely to be HPV-positive (N=30 [81.1%]) than the HIV-negative veterans with OPSCC (N=50 [67.6%]), although this difference was not significant (p=.135). For nonoropharyngeal cancer, the increased risk of oral cavity cancer among VLWH drove the increased risk. The study results suggest that HIV may play a role in virally mediated and nonvirally mediated HNSCC. As the HIV prevalence rises in the United States due to better survival and the incidence of HPV-positive oropharyngeal HNSCC increases, the interaction between HPV and HIV becomes increasingly relevant.

Head and Neck Cancer Stage at Presentation and Survival Outcomes Among Native Hawaiian and Other Pacific Islander Patients Compared With Asian and White Patients

Research studies often group Native Hawaiian and Other Pacific Islander individuals together with Asian individuals despite being consistently identified as having worse health outcomes and higher rates of comorbidities and mortality. Native Hawaiian and Other Pacific Islander individuals also have high incidence rates of oral cavity and pharyngeal cancer compared with the general population; however, disparities in clinical presentation and survival outcomes of head and neck cancer squamous cell carcinoma (HNSCC) among this population have not been investigated nor compared with those of other races. To determine the association of race with cancer stage at diagnosis and survival outcomes among Native Hawaiian and Other Pacific Islander patients with HNSCC compared with Asian and non-Hispanic White patients. This was a retrospective population-based cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) 18 database. Asian, Native Hawaiian or Other Pacific Islander, and non-Hispanic White adult patients diagnosed in 1988 through 2015 with HNSCC of the oral cavity, oropharynx, nasopharynx, larynx, and hypopharynx were included; any patient whose record was missing data on disease or demographic information was excluded. Cancer stage at presentation was compared among Asian, Native Hawaiian and Other Pacific Islander, and non-Hispanic White patients using a multivariable logistic regression model. Survival outcomes were compared among these racial groups using Cox regression models. Data analyses were performed from July 1, 2021, to March 20, 2022. The total study population comprised 76 473 patients: 4894 Asian (mean [SD] age at presentation, 60.7 [14.6] years), 469 Native Hawaiian and Other Pacific Islander (57.8 [12.3] years), and 71 110 non-Hispanic White (62.2 [12.1] years) individuals. Native Hawaiian and Other Pacific Islander patients were more likely to present with advanced-stage HNSCC (odds ratio [OR], 1.38; 95% CI, 1.12 -1.72) compared with non-Hispanic White patients. Asian patients presented with similar stage disease (OR, 1.04; 95% CI, 0.97-1.11) compared with non-Hispanic White patients. Native Hawaiian and Other Pacific Islander patients had worse disease-specific survival (HR, 1.18; 95% CI, 1.02-1.36) compared with non-Hispanic White patients after adjusting for clinical and demographic factors. In contrast, Asian patients had improved disease-specific survival (HR, 0.93; 95% CI, 0.88-0.98) compared with non-Hispanic White patients. This retrospective population-based cohort study suggests that Native Hawaiian and Other Pacific Islander race was associated with more advanced HNSCC, and worse disease-specific survival compared with non-Hispanic White race, while Asian race was associated with improved survival. This study highlights the importance of disaggregating Asian from Pacific Islander data when assessing health disparities, and the need for culturally sensitive interventions to promote earlier detection of head and neck cancer and improved survival among the Native Hawaiian and Other Pacific Islander population.

Cannabis Use in Patients with Head and Neck Cancer and Radiotherapy Outcomes

<h3>Purpose/Objective(s)</h3> Marijuana use in the population is increasing as states continue to allow for both medicinal and recreational use. As such, the prevalence of marijuana use among patients presenting for treatment of head and neck cancer (HNC) is likely to increase as well. Anecdotally, patients are asking about marijuana use during cancer treatment and, to date, oncology professionals treating HNC are lacking sufficient data to aid in advising their patients on use during cancer care. Further, the impact of marijuana use on survival and local control in HNC is not well understood. The current study examines the associations between marijuana use and the management and outcomes in patients with HNC squamous cell carcinoma. <h3>Materials/Methods</h3> IRB approval was obtained for a retrospective evaluation in our institutional database. Two-hundred eighty patients with detailed psychosocial and substance abuse history who were treated with either definitive or adjuvant radiotherapy between August 2018 and March 2020 were included in the analyses. Overall survival (OS) and disease-free survival (DFS) were compared between current marijuana users and non-users using Kaplan-Meier curves and log-rank tests. <h3>Results</h3> 148 patients with HNC were included (mean age=62.1 yrs, SD=9.1), 78% were male, 73% were white, 22% were black. 62% of patients had SCCa of the oropharynx, 20% SCCa of the larynx, and 14% SCCa of the oral cavity. 51% were treated with definitive chemoradiotherapy, while 32% had primary surgery. 30% were current tobacco users and 70% had ever used tobacco (mean = 43.33 PY). 15% of patients reported marijuana use at time of initial diagnosis and 34% reported a history of marijuana use. Older patients and males were more likely to be currently using marijuana (p=.005 & p=.04, respectively). Current marijuana users were more likely to require narcotic pain medications and require a greater number of types of pain medications during treatment (p=0.002 and p=0.007, respectively). There were no differences between current and historical/never users on self-reported worst pain, weight loss or enteral feeding tube use during treatment, or objective measures of treatment toxicity. Additionally, there were no other significant differences between current or historical/never users were found on cancer variables or primary treatment type. <h3>Conclusion</h3> Marijuana use in patients with HNSCCa is common and little is known about patient and oncological outcomes. There were no significant differences between current and past marijuana users and non-users on clinicopathological variables, adherence, or oncologic outcomes. Marijuana use in HNC may result in more difficulty managing pain during treatment. Further research is needed to better understand marijuana use during cancer treatment, particularly frequency and method of use (i.e., smoking vs. edibles/oils), outcomes, and quality of life.

5-aza-2'-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line.

Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, resulting in over 600,000 new diagnoses annually. Traditionally, HNCC has been related to tobacco and alcohol exposure; however, over the past decade, a growing number of head and neck cancers are attributed to human papillomavirus (HPV) infection. 5-Aza-2’-deoxycytidine (5-AzaD) was demonstrated as an effective chemotherapeutic agent for acute myelogenous leukaemia. Preclinical data revealed that 5-aza inhibits growth and increases cell death of HPV(+) cancer cells. These effects are associated with reduced expression of HPV genes, stabilization of TP53, and activation of TP53-dependent apoptosis. The aim of the present study is to test the effect of 5-AzaD on growth of human squamous cell carcinoma (FaDu), a HPV(-) and p53 mutated cells, in vitro and in vivo. The effect of 5-AzaD on cell viability, cell cycle progression and induction of apoptosis was tested in vitro. The effect of 5-AzaD on tumour growth in vivo was tested using xenograft mice inoculated with FaDu cells. The results indicated that 5-AzaD reduced cell viability and induced apoptosis in FaDu cells in vitro. In vivo studies revealed that 5-AzaD suppresses the growth of tumours in xenograft mice inoculated with FaDu cells through inhibition of proliferation and induction of apoptosis. These findings may emphasis that 5-AzaD is effective in treatment of HPV(-) HNSCC tumours through TP53 independent pathway. Future studies are needed in order to clarify the molecular mechanism of action of 5-AzaD in HPV(-) cancer cells.

919P Survival impact of nutritional status of locally advanced head and neck cancer squamous cell carcinoma (HNSCC) patients treated with chemoradiotherapy: A prospective observational study

Though weight loss (WL) and poor treatment outcomes of chemoradiotherapy (CRT) in locally advanced HNSCC patients was previously reported, nutritional status during CRT has not been well studied. Thus, we prospectively evaluated long term nutritional status of HNSCC patients who underwent CRT and correlated with treatment outcomes.

Glutaminase inhibition with telaglenastat (CB-839) improves treatment response in combination with ionizing radiation in head and neck squamous cell carcinoma models.

The efficacy of ionizing radiation (IR) for head and neck cancer squamous cell carcinoma (HNSCC) is limited by poorly understood mechanisms of adaptive radioresistance. Elevated glutaminase gene expression is linked to significantly reduced survival (p<0.03). The glutaminase inhibitor, telaglenastat (CB-839), has been tested in Phase I/II cancer trials and is well tolerated by patients. This study investigated if telaglenastat enhances the cellular response to IR in HNSCC models. Using three human HNSCC cell lines and two xenograft mouse models, we examined telaglenastat's effects on radiation sensitivity. IR and telaglenastat combinatorial treatment reduced cell survival (p≤0.05), spheroid size (p≤0.0001) and tumor growth in CAL-27 xenograft bearing mice relative to vehicle (p≤0.01), telaglenastat (p≤0.05) or IR (p≤0.01) monotherapy. Telaglenastat significantly reduced the Oxygen Consumption Rate/Extracellular Acidification Rate ratio in CAL-27 and HN5 cells in the presence of glucose and glutamine (p≤0.0001). Telaglenastat increased oxidative stress and DNA damage in irradiated CAL-27cells. These data suggest that combination treatment with IR and telaglenastat leads to an enhanced anti-tumor response. This pre-clinical data, combined with the established safety of telaglenastat justifies further investigation for the combination in HNSCC patients.

Mass Cytometry for Comprehensive Profiling of Systemic Immune Composition in Head and Neck Squamous Cell Carcinoma Patients Reveals Dynamic Changes Early in Therapy

We hypothesized that peripheral blood from patients undergoing RT would demonstrate quantifiable changes in immune cell composition early during therapy, and that some of these features would ultimately correlate with clinical outcomes. To this end, we leveraged mass cytometry (CyTOF) to comprehensively profile all major immune subpopulations in peripheral blood of head and neck cancer (HNC) patients before and up to two weeks after initiation of RT. As a pilot, we obtained peripheral blood samples from 5 patients with HNC and 5 healthy control patients. For cancer patients, samples were acquired prior to initiation of any therapy, prior to fraction 4 and prior to fraction 9 of RT. Samples were barcoded and stained using a panel of 40 metal-conjugated antibodies prior to data acquisition on Helios mass cytometer (Fluidigm). Debarcoded and normalized data were analyzed by UMAP dimensionality reduction and unsupervised segmentation using CLARA (Clustering Large Applications). Cancer patients had a median age of 60 (range 49-67), HNC squamous cell carcinoma (2 tonsil, 1 base of tongue, 1 glottic larynx, 1 unknown primary), locoregionally advanced disease, and median RT fraction size of 212 cGy. The majority of patients had p16+ HNC (3) and received concurrent platinum-based chemotherapy (4). All patients had primary and nodal disease in situ at time of radiation. Neutrophils predominated in whole blood as expected (71.9% controls, 80.6% patients, p = 0.056). When analysis was limited to non-neutrophils, 16 immune subpopulations were additionally identified via unsupervised clustering. At baseline, there were no differences in proportions of most subsets except for an increase in regulatory T cells (Tregs, p = 0.016) and decreases in naïve CD8 T cells (p = 0.032) and gdT cells (p = 0.016) in cancer patients as compared to healthy controls. However, Post-RT samples displayed dynamic and divergent changes in cell frequencies. 3 patients demonstrated up to a 5.6-fold increase in CD14+ HLA-DR-/lo monocytes (often referred to as monocytic myeloid-derived suppressor cells or M-MDSCs) typically associated with immunosuppression. Type 2 conventional dendritic cells, critical mediators of antigen cross-presentation, were increased in 3 patients, stable in 1 patient and decreased in 1 patient. Interestingly, Treg frequency was dramatically reduced at timepoint 2 before returning to near baseline levels at timepoint 3, a pattern seen in 4 patients. Major immune subpopulations can be robustly quantified in pre- and post-RT whole blood samples using CyTOF and patterns of change were evident even in a small number of patients. Dynamic changes in immune cell composition are notable even within 1-2 weeks of RT initiation. More detailed correlation with treatment regimens and therapeutic outcomes in a larger patient cohort may allow identification of prognostic immunologic biomarkers.

Abstract B085: Disparities and factors associated with 30-day mortality following surgical treatment for squamous cell head and neck cancer with or without adjuvant therapy

Abstract Introduction: Factors such as anatomic complexity and extensive surgical procedures increase the risk of serious, sometimes fatal complications post-surgical treatment for head and neck cancer squamous cell carcinoma (HNSCC). Thirty-day (30-day) mortality is a common quality metric that evaluates short-term survival; however, no study has described disparities associated with 30-day mortality following surgery in HNSCC United States population. The aim of this study was to identify disparities and factors (clinical and nonclinical) associated with 30-day postoperative mortality in patients with HNSCC treated with and without adjuvant therapy. Methods: In this retrospective study, we utilized a patient cohort of 102,877 confirmed HNSCC cases from the National Cancer Database (2004-2013) who were treated surgically with curative intent for the primary head and neck cancer. The effects of adjuvant therapy and other clinical and nonclinical factors on 30-day postoperative mortality were estimated via multivariate logistic regression with adjustment for time-varying nature of adjuvant therapy. Outcome was defined as any-cause-death within 30 days after definitive surgery of primary cancer. We controlled for several clinical and nonclinical covariates, including age, race, sex, health insurance status, primary tumor site, stage of presentation, and Charlson-Deyo comorbidity score. Results: There were 859 patients who died within 30 days of definitive surgery for cancer, yielding a 30-day mortality rate of 0.83%. Treatment differences were associated with mortality, and patients who received adjuvant therapy had were significantly more likely to die within 30 days compared with those treated with surgery alone (aOR: 3.51; 95% CI 1.85, 6.66). Increasing number of comorbidities was also associated with greater odds of 30-day mortality (Charlson-Deyo comorbidity scores of 1: aOR: 1.45; 95% CI 1.23, 1.71, and Charlson-Deyo comorbidity scores of 2+ aOR: 2.52; 95% CI 2.05, 3.09). There were also sociodemographic disparities associated with 30-day mortality. Odds of 30-day mortality were significantly increased among patients with Medicaid insurance (aOR: 1.99; 95% CI 1.48, 2.68), as well as those who lived in neighborhoods with little education (≥ 29% missing high school diploma: aOR: 1.43; 95% CI 1.08, 1.88). Conclusions: Disparities impact short-term mortality in the head and neck cancer population. Patients that were significantly more likely to die within 30 days of surgical treatment were those treated with adjuvant therapy, those with greater burden of comorbidities, those with little education, and those covered by Medicaid. To our knowledge, this is the largest study to document short term (30-day) mortality disparities among patients with head and neck cancer post-surgery in the United States. To improve short-term survival among head and neck cancer patients, it is important to account for these disparities found in this study. Citation Format: Aleksandr R. Bukatko, Parth Patel, Vindhya Kakarla, Matthew C. Simpson, Eric A. Boakye, Katherine A. Stamatakis, Nosayaba Osazuwa-Peters. Disparities and factors associated with 30-day mortality following surgical treatment for squamous cell head and neck cancer with or without adjuvant therapy [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B085.

Human papillomavirus insertions identify the PIM family of serine/threonine kinases as targetable driver genes in head and neck squamous cell carcinoma.

Human papillomavirus (HPV) insertions in cancer genomes have been linked to various forms of focal genomic instability and altered expression of neighboring genes. Here we tested the hypothesis that investigation of HPV insertions in a head and neck cancer squamous cell carcinoma (HNSCC) cell line would identify targetable driver genes contributing to oncogenesis of other HNSCC. In the cell line UPCI:SCC090 HPV16 integration amplified the PIM1 serine/threonine kinase gene ~16-fold, thereby increasing transcript and protein levels. We used genetic and pharmacological approaches to inhibit PIM kinases in this and other HNSCC cell lines. Knockdown of PIM1 transcripts by transfected short hairpin RNAs reduced UPCI:SCC090 viability. CRISPR/Cas9-mediated mutagenesis of PIM1 caused cell cycle arrest and apoptosis. Pharmacological inhibition of PIM family kinases decreased growth of UPCI:SCC090 and additional HNSCC cell lines in vitro and a xenograft UPCI:SCC090 model in vivo. Based on established interactions between intracellular signaling pathways and relatively high levels of gene expression in almost all HNSCC, we also evaluated combinations of PIM kinase and epidermal growth factor receptor (EGFR) inhibitors. Dual inhibition of these pathways resulted in supra-additive cell death. These data support clinical testing of PIM inhibitors alone or in combination in HNSCC.

Epidemiologic Characteristics of Squamous Head and Neck Carcinoma Patients. Results of a Hospital Register

Introduction and objectivesThe epidemiological characteristics of patients with head and neck cancer squamous cell carcinoma (HNSCC) have changed over recent years. The increase in life expectancy of the population, changed patterns of tobacco and alcohol use, and human papillomavirus infection (HPV) have brought about significant changes. The objective of the present study is to analyze the changes in the epidemiological and clinical characteristics of these patients over a 30-year period. MethodsRetrospective study of 5123 patients with HNSCC treated over the period 1985–2017. We evaluated the existence of changes in the patterns of age, sex, tobacco and alcohol use, and location and extension of the tumours throughout the study period. HPV status was evaluated for patients with oropharyngeal carcinomas. ResultsThroughout the study period there was a significant increase in the mean age at presentation and in the percentage of women, and a decrease in the percentage of patients with history of high consumption of toxic substances. We observed a decrease in the proportion of patients with laryngeal cancer, and an increase of patients with early tumours cT1 and with neck disease cN2. We detected a progressive increase in the proportion of HPV-positive oropharyngeal carcinoma patients. ConclusionOver recent decades there have been significant changes in the epidemiological and clinical characteristics of patients with HNSCC.

Abstract 2527: Genomic aberrations of ALK in head and neck squamous cell carcinoma

Abstract Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase encoded by the gene ALK, which belongs to a subfamily of the insulin receptor superfamily. ALK signaling has been shown to be involved in cell proliferation, differentiation, and development, etc. Thus far, ALK aberrations are known to be involved in the oncogenesis of non-small cell lung cancer and glioblastoma. Head and neck cancer squamous cell carcinoma (HNSCC) is an aggressive cancer with genomic heterogeneity as revealed by recent whole-exome studies. Though ALK aberrations are found in a notable subset of HNSCC, their biological importance is largely unknown. Comprehensive pan-cancer analysis of 33 cancer types (TCGA, Pan-cancer, Provisional, N=11617, www.cbioportal.org) showed that ALK aberrations (mutations, amplification and gene copy gain) are commonly noted in 27 cancers, with HNSCC ranking 9th having ~22% cases of primary tumors harboring these ALK genomic aberrations. Within the US TCGA HNSCC dataset (Provisional; N=510), 3.5% of HNSCC patient tumors harbor somatic ALK mutations, 0.4% cases with ALK amplification, and 17.4% cases with ALK gain. Further, RNA-seq analysis revealed tumor specific ALK mRNA upregulation in 43 pairs of normal-tumor tissues (~2-fold, P=0.001***), and 457 HNSCC tumors (~1.5-fold, P=0.039*). There are currently 172261 single-nucleotide polymorphism (SNP) on ALK exons in human reported in the dbSNP database. We noted 18.9% of Asian HNSCC patients (N=53) bearing ALK germline variants (N=10) with unknown clinical significance. Interestingly, ALK aberrations (mutations, amplification, gene copy gain) are noted to be significantly associated with TP53 mutations (P&amp;lt;0.0001), HPV-negativity (P=0.0094) and the male gender (P=0.0041; Fisher’s Exact test), but not associated with HNSCC patient survival (P=0.734). Further, patients with ALK mutation and amplification are largely advanced cases (93.33%, Stage III and Stage IV). Gene Set Enrichment Analysis (GSEA) of mRNA expression shows that ALK-altered HNSCC tumors (vs unaltered tumors) appear to have significantly downregulation of immune response gene set [NES (normalized enrichment score)=-6.773, P=0.0026] and inflammatory response gene set (NES=-5.54, P= 0.0022), while nervous system development and cell development signaling gene sets are significantly upregulated (P=0.0015, 0.0016, respectively). Proteomic analysis (TCPA, N=209) showed that ALK-altered HNSCC (vs. -unaltered tumors) have increased PIK3CA and CHEK2 protein expression (P&amp;lt;0.001, 0.0001, respectively), as well as reduced PRAS40(pT246) and VEGFR2 protein expression (P&amp;lt;0.001, 0.001, respectively). In conclusion, ALK aberrations may contribute to HNSCC aggressiveness, potentially via reduction of immune response and activation of PI3K signaling pathway. Future investigations studying the biological effects of ALK aberrations on HNSCC oncogenesis are warranted. Citation Format: Lan Wang, Yuchen Liu, Wenying Piao, Peony Hiu Yan Poon, Chun Kit Yeung, Amy Bik Wan Chan, Chin Wang Lau, Yuxiong Su, Jason Ying Kuen Chan, Vivian Wai Yan Lui. Genomic aberrations of ALK in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2527.

Abstract 3828: Differential transcriptional response of MYC to bromodomain inhibition in HPV positive head and neck squamous cell carcinoma

Abstract Differential transcriptional response of MYC to bromodomain inhibition in HPV positive head and neck squamous cell carcinoma Targeting of bromodomain (BRD) and extra-terminal domain (BET) family protein activity has the potential to reduce proliferation in many cancers. We hypothesize that targeting BRDs using its inhibitors will lead to reduced proliferation in human papilloma virus (HPV) infected head and neck cancer squamous cell carcinoma (HNSCC). HPV infected HNSCC is predicted to surpass the incidence of cervical cancer by 2020. Amongst various HPV serotypes, HPV16 is classified as oncogenic for a various number of cancer sites including head and neck squamous cell carcinoma (HNSCC). Integration of HPV into host genomes is not part of its life cycle; however, the exception is HNSCC wherein E6 and E7 viral proteins predominantly drive its tumor progression. HPV integrated HNSCC cells will be utilized to unravel the fundamental question of epigenetic regulation of viral-host interaction using the HPV-positive HNSCC model. Results from our lab indicate that despite high nanomolar IC50 in cell proliferation assays, downregulation of MYC expression was not observed using BRD inhibitor in all MYC expressing HNSCC cell lines. Further interrogation revealed differential phosphorylation of tumor suppressors - p53 and pRb might influence the sensitivity to BRD inhibition, which in turn could explain the contrasting regulation of MYC RNA levels. Intriguingly, combining radiation with bromodomain inhibitors led to increased radio-sensitization suggesting that BRDs have a role to play in DNA damage repair pathway and altered cell cycle regulation. Taken together, we will present MYC dependent and independent mechanism following BRD inhibition in HPV positive HNSCC. Note: This abstract was not presented at the meeting. Citation Format: Hassler Rengifo, Albert R. Wang, Mohammad Titi, Kwang Nickel, Randy Kimple, Gopal Iyer. Differential transcriptional response of MYC to bromodomain inhibition in HPV positive head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3828.

Características epidemiológicas de los pacientes con carcinomas escamosos de cabeza y cuello. Resultados de un registro hospitalario

Introduction and objectivesThe epidemiological characteristics of patients with head and neck cancer squamous cell carcinoma (HNSCC) have changed over recent years. The increase in life expectancy of the population, changed patterns of tobacco and alcohol use, and human papillomavirus infection (HPV) have brought about significant changes. The objective of the present study is to analyze the changes in the epidemiological and clinical characteristics of these patients over a 30-year period. MethodsRetrospective study of 5,123 patients with HNSCC treated over the period 1985-2017. We evaluated the existence of changes in the patterns of age, sex, tobacco and alcohol use, and location and extension of the tumours throughout the study period. HPV status was evaluated for patients with oropharyngeal carcinomas. ResultsThroughout the study period there was a significant increase in the mean age at presentation and in the percentage of women, and a decrease in the percentage of patients with history of high consumption of toxic substances. We observed a decrease in the proportion of patients with laryngeal cancer, and an increase of patients with early tumours cT1 and with neck disease cN2. We detected a progressive increase in the proportion of HPV-positive oropharyngeal carcinoma patients. ConclusionOver recent decades there have been significant changes in the epidemiological and clinical characteristics of patients with HNSCC.

CD44 expression at the invasive tumor front: effect on patterning and prognosis in head and neck cancer

The invasive tumor front (ITF) and pattern of invasion (POI) are significant prognosticators in head and neck cancer squamous cell carcinoma (HNSCC); this study evaluates the expression of CSC marker, CD44 at the ITF and their combined prognostic potential. POI, as scored by the invasive pattern grading score (IPGS), was correlated with CD44 expression in HNSCC cell line-derived xenografts. Immunohistochemical expression of CD44 was correlated with the ITF features in patients and their combined prognostic ability assessed by multivariate analysis, Kaplan–Meier plots, and Cox regression models. Assessment of cell line-derived in vivo models indicated that drug-resistant, CD44-enriched cell lines led to generation of xenografts with aggressive POIs (IV) at the ITF. In patients (N = 173), a near significant association of CD44 with IPGS (p = 0.05) was observed. CD44 (p = 0.02), along with differentiation (p = 0.04), and lymphoplasmocytic infiltration (LPI) (p = 0.03) were independent prognosticators of recurrence. Notably, IPGS and poorly differentiated tumors were predictors of recurrence in CD44high cohort (p < 0.05), while severe LPI was a good prognosticator only in CD44low cohort (p < 0.006). In the treatment naive cohort, the prognostic efficacy was confined to the early stage patients (p < 0.007). A multifactorial risk model significantly stratified patients based on outcome (p = 0.029). CD44+ CSCs at the ITF correlated with aggressive POI and both factors together were poor prognosticators of HNSCC.