Enteral nutrition support and treatment toxicities in patients with head and neck cancer receiving definitive or adjuvant helical intensity-modulated radiotherapy with concurrent chemotherapy.

BACKGROUND: Enteral nutrition (EN) is often required in patients with head and neck cancer (HNSCC); however, initiation criteria is limited or inconsistent. This study aimed to describe the relationship of treatment toxicities and requirement for EN and investigate toxicity and baseline characteristics association with EN duration. METHODS: Acute toxicities and baseline characteristics were collected from patients with HNSCC (n = 110) undergoing H-IMRT. Percentage EN contributing to estimated requirements and EN duration were measured. RESULTS: The threshold for patients needing ≥50% of estimated requirements via EN increased from week 3 to 4 for grade ≥2 oral/pharyngeal mucositis, dysgeusia, thick saliva and nausea, and for grade 3 dysphagia. Patients with grade 2-3 dysphagia had a reduced risk of ceasing EN compared to those with grade 0-1 dysphagia. CONCLUSIONS: Using acute toxicities in clinical practice may be a useful tool to inform prompt initiation of EN prior to decline in nutritional status and anticipate EN duration.

Cumulative Coffee Consumption as a Protective Factor for Head and Neck Cancer in Brazil.

There is still no consensus in the literature regarding the role of coffee in head and neck cancer. Thus, we sought to analyze the cumulative consumption of coffee as a protective factor in the genesis of head and neck cancer in Brazil, one of the main coffee producing countries, from January 2011 to February 2017. We carried out a case-control study in 5 referral centers for head and neck cancer with 839 cases and 842 non-cancer hospital controls matched by sex, data collection center and age group. The results of logistic regression analysis showed that the cumulative consumption of >2 cups of coffee per day is an important protective factor (OR: 0.73, 95% CI: 0.5-0.9) against head and neck cancer. Smoking increased the risk by 22 times (OR: 22.19; 95% CI: 13.7-35.8) in individuals who smoke more than 50 packs per year, and the habit of ingesting more than 155 ml of alcohol per day represented approximately twice as high risk (OR: 2.20; 95% CI: 1.4-3.4). In summary, this study suggests that coffee consumption is associated with a lower chance of head and neck cancer.

Oral and dental care before radiotherapy: Guidelines and development of a time-bound protocol.

Involvement of multidisciplinary team is the mainstay in the holistic treatment outcome in head and neck cancer patients. Achieving a state of oral health is regarded as an essential treatment goal before radiation therapy but, it may get overlooked due to many competing priorities, lack of multidisciplinary facilities and/or incoordination, and limited overall awareness with regards to means of achieving oral health and in a time-bound manner and its relevance in improving quality of life in cancer survivors. Radiation inflicts an immense amount of damage upon the entire maxillofacial complex and consequently oral treatment after radiotherapy may remain untreated and/or undertreated. It is, therefore, vital to eliminate oral foci of infections well within a time frame before radiation so that tumor prognosis is not compromised.This article describes the current guidelines combined with a time-bound protocol developed in our center to not only prepare a patient for conventional radiotherapy but also to provide a logical perspective towards the feasibility of the oral rehabilitation post-cancer cure. The protocol aims to maximize the quality of life in head and neck cancer survivors by; patient education, minimizing preventable oral complications, and retaining strategic teeth for function, aesthetics, speech, and prosthetic support. The time-bound pre-radiation oral care protocol is rational, achievable, and is aligned towards the sustained oral health care goals in head and neck cancer patients and can be utilized as a useful resource in multidisciplinary head and neck cancer care facilities.

The impact of hyperbaric oxygen therapy on late irradiation injury in oral microcirculation.

BACKGROUND: Late side effects of radiotherapy in patients with head and neck cancer (HNCPs) result in decreased tissue vascularity, a compromised healing capacity and spontaneous breakdown of tissue. The aim of this study was to examine the in vivo effect of hyperbaric oxygen therapy (HBOT) on the microcirculation in irradiated oral tissue. METHODS: Using a handheld microscope, the effect of HBOT on oral mucosal microcirculation parameters was measured in 34 previously irradiated HNCPs prior to HBOT and at 4 weeks and 6 months posttreatment. RESULTS: A significant increase in mean buccal vessel density and decrease in buccal vessel diameter was found 6 months after HBOT compared to baseline, 22 ± 11 versus 25 ± 7 cpll/mm2 (p < 0.05) and 20 ± 4 versus 16 ± 5 µm (p < 0.05), respectively. CONCLUSION: Our results indicate that oral microcirculation histopathology associated with irradiation is able to respond to HBOT by redirecting oral microcirculation parameters towards values consistent with healthy tissue.

Serum zinc status and the development of mucositis and dermatitis in head-and-neck cancer patients undergoing curative radiotherapy: A pilot study.

Background: Radiation-induced mucositis and dermatitis are severe side effects and compromise the health of the head-and-neck cancer patient undergoing treatment. Zinc supplementation during the course of the treatment is shown to have protective effects against both radiation-induced mucositis and dermatitis. The aim of this study was to understand whether the level of serum zinc has an effect on the development of mucositis and dermatitis. Materials and Methods: This was noninterventional study where the levels of serum zinc were ascertained before the start of treatment by spectrophotometric methods. The patients were treated every day with no more than one fraction of 2 Gy per day, five times a week without any intended gaps for a planned target dose of 60-70 Gy (6-7 consecutive weeks). The patients were assessed for radiation-induced dermatitis and mucositis in accordance with the standard guidelines. The association between the levels of serum zinc with the development of different grades of mucositis and dermatitis (on the day of development) was ascertained using the Pearson correlation coefficient (r). A statistical value of P < 0.05 was considered to be statistically significant. Results: A total of 52 consecutive patients satisfying the inclusion criteria were enrolled. The results indicate that serum zinc levels showed a significant correlation (r = 0.29; P < 0.038) for Grade 1, while it was insignificant for Grades 2 and 3. For dermatitis, a significant correlation for all the grades (Grade 1 [r = 0.28; P < 0.043]; Grade 2 [r = 0.39; P < 0.006]; and Grade 3 [r = 0.49; P < 0.047]) was observed. Conclusions: For the first time, the results of this pilot study indicate that the serum level of zinc had an inverse association with the early development of mucositis and dermatitis, with better effects seen in dermatitis where it was also effective in Grades 2 and 3.

A European survey on the practice of nutritional interventions in head-neck cancer patients undergoing curative treatment with radio(chemo)therapy.

PURPOSE: As the practice of nutritional support in patients with head and neck cancer (HNC) during curative radio(chemo)therapy is quite heterogeneous, we carried out a survey among European specialists. METHODS: A 19-item questionnaire was drawn up and disseminated via the web by European scientific societies involved in HNC and nutrition. RESULTS: Among 220 responses, the first choice was always for the enteral route; naso-enteral tube feeding was preferred to gastrostomy in the short term, while the opposite for period longer than 1 month. Indications were not solely related to the patient's nutritional status, but also to the potential burden of the therapy. CONCLUSION: European HNC specialists contextualize the use of the nutritional support in a comprehensive plan of therapy. There is still uncertainty relating to the role of naso-enteral feeding versus gastrostomy feeding in patients requiring < 1 month nutritional support, an issue that should be further investigated.

Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Cancer and how the patients see it; prevalence and perception of risk factors: a cross-sectional survey from a tertiary care centre of Karachi, Pakistan.

BACKGROUND: The incidence of cancer is rising but data available regarding prevalence of cancer and patient perception of the disease in Pakistan is limited. It is difficult to deal with Cancer if the main causes are negligence towards risk factors and bizarre myths. This study was aimed to investigate common cancer presentations at a government sector hospital and to gain insight into patient knowledge of the disease. METHODS: This was a cross-sectional study conducted on cancer patients from Jinnah Postgraduate Medical Centre. A self-made questionnaire was used to assess the norms related to cancer prevalence in our society, associated myths, and the most common risk factors per them. RESULTS: A total of 402 participants consented to participate in the study (mean age 42.3 ± 15.07 years), 204(50.7%) were females and 190(47.3%) were illiterate. Biomass exposure was found in 147(37%), drug abuse in 132(33%) and smoking in 63(16%). We found 103(25.6%) had positive family histories of cancer. The most common primary tumor site was breast for females 98(48%) and Head and neck 66(33.3%) for males. Patients considered fate 328(82%), gutka 284(71%) and injuries 282(70%) as the most common causes for cancer; while 222(55.5%) considered black magic and 236(58.75%) considered evil eye as a risk factor for cancer. Cancer treatment caused significant financial stress in 376(93.5%) patients. CONCLUSION: Breast and head and neck cancers were found to be prevalent among patients. It was noted that patients are negligent in daily life regarding the consumption of substances that commonly cause cancer. Individuals had diminished knowledge and majority linked cancer to unrelated causes and myths like black magic and fate. Almost all the patients complained of severe financial stress imposed by the disease.

Fish/shellfish intake and the risk of head and neck cancer.

Fish intake and other dietary sources of omega-3 fatty acids have been shown to be associated with a reduced risk for some cancers. Although previous studies of head and neck cancer have reported associations with different dietary factors, including reduced risks for fruits and vegetables and putatively healthy dietary patterns, associations specific to fish intake are unclear. This study investigated the association between fish/shellfish intake and risk of squamous cell carcinoma of the head and neck (SCCHN) using data from the Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study conducted in 46 North Carolina counties with cases recruited from 2002 through 2006. Controls were frequency matched to the cases on age, sex, and race; the final sample size was 1039 cases and 1375 controls. Demographic, lifestyle, and dietary information were collected using an in-person interviewer-administered structured questionnaire. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with unconditional logistic regression. Patients whose fish/shellfish intake was among the highest tertile had a 20% lower odds of SCCHN compared with those in the lowest tertile (OR: 0.80; 95% CI: 0.60-1.07) after adjustment for the matching and other factors (income, energy intake, fruit intake, cigarette smoking, and alcohol intake). The inverse association was more pronounced for oral cavity and oropharyngeal tumors, for African Americans, and for females, but CIs were wide. To further investigate this potential risk reduction strategy for SCCHN, future studies should consider examining specific fish/shellfish, cooking practices, and other omega-3 fatty acid sources.

[Smoking and alcohol cessation programs in patients with head and neck cancer]. / Accompagnement des dépendances à l'alcool et au tabac des patients atteints d'un cancer des voies aérodigestives supérieures.

Most head and neck cancers are associated with smoking and alcohol exposure. Smoking and alcohol cessation (ASC) is associated with improved quality of life, cancer therapy efficacy, decreased treatment-related and cardiovascular risks, and is expected to decrease the risk of second primary tumor. It is therefore a high priority in the plan of care. However, results of current ASC programs are disappointing and understanding the reasons of this is critical. We started a qualitative study in 6 academic centers including 3 university hospitals, one regional hospital and one comprehensive cancer center. We first interviewed surgeons and care givers involved in the management of head and neck cancers. Poor communication between stakeholders, absence of alignment of care goals between patients, surgeons and other caregivers, and low level of understanding by patients of the benefits of ASC were felt to represent frequent obstacles to successful outcome. More work is ongoing within the context of our IHNPACT umbrella protocol to identify hurdles associated with successful ASC.

Vitamin D intake and survival and recurrence in head and neck cancer patients.

OBJECTIVES/HYPOTHESIS: With an unacceptably low 5-year survival rate and few identified modifiable factors that affect head and neck cancer (HNC) outcomes, HNC survival remains an important public health problem. Vitamin D has been shown to be associated with immune reactivity and improved outcomes for some cancer sites, but findings are mixed, and few studies have examined vitamin D in relation to HNC. This study aimed to assess the association between vitamin D intake and survival outcomes in HNC patients. STUDY DESIGN: Prospective cohort study. METHODS: This study utilized data on 434 HNC patients with valid pretreatment food frequency questionnaire data who participated in the University of Michigan Head and Neck Specialized Program of Research Excellence epidemiology project. Cox proportional hazard models were used to estimate the associations between total, dietary, and supplemental vitamin D intake and HNC outcomes, while adjusting for other known prognostic factors. RESULTS: After multivariable adjustment, we found a statistically significant inverse trend between total vitamin D intake and recurrence (Q4 vs. Q1 hazard ratio: 0.47, 95% confidence interval: 0.20-1.10, P trend = .048). We observed no association with dietary or supplemental intake separately, and no association was observed with all-cause or HNC-specific mortality. CONCLUSIONS: These findings suggest that HNC patients with lower levels of vitamin D intake are at higher risk of recurrence. If borne out in future studies, our results suggest that increased vitamin D intake through dietary intervention or the use of supplements may be a feasible intervention for prevention of recurrence in HNC patients. LEVEL OF EVIDENCE: 2b. Laryngoscope, E371-E376, 2018.

Head and neck cancers in India.

Head and neck cancers constitute a third of the cancer burden in India. These cancers have unique patient characteristics, presentation, and etiological differences from those in the West. Socioeconomic constraints, large patient population, scarcity of trained health workers, and inadequate infrastructure are major challenges faced in the management of these cancers. Despite these constraints, patients are treated with evidence based guidelines that are tailored to the local scenario.

Prospective study of serum cysteine and cysteinylglycine and cancer of the head and neck, esophagus, and stomach in a cohort of male smokers.

BACKGROUND: The nonessential amino acid cysteine is known to be involved in many antioxidant and anticarcinogenic pathways. Cysteinylglycine is a pro-oxidant metabolite of glutathione and a precursor of cysteine. OBJECTIVE: To examine the relation between serum cysteine and cysteinylglycine and risk of gastric adenocarcinomas, esophageal squamous cell carcinomas, and head and neck squamous cell carcinomas, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention study of male Finnish smokers aged 50-69 y at baseline. DESIGN: In total, 170 gastric adenocarcinomas, 68 esophageal squamous cell carcinomas, and 270 head and neck squamous cell carcinomas (identified from the Finnish Cancer Registry) were matched one-to-one with cancer-free control subjects on age and the date of serum collection. We calculated ORs and 95% CIs with the use of a multivariate-adjusted conditional logistic regression. RESULTS: Cysteine had a U-shaped association with gastric adenocarcinomas; a model that included a linear and a squared term had a significant global P-test (P = 0.036). Serum cysteinylglycine was inversely associated with adenocarcinomas of the gastric cardia (OR for above the median compared with below the median: 0.07; 95% CI: 0.01, 0.70; n = 38 cases) but not for other sites. Both cysteine and cysteinylglycine were not associated with esophageal squamous cell carcinoma or head and neck squamous cell carcinoma. CONCLUSIONS: We observed associations between serum cysteine and cysteinylglycine with upper gastrointestinal cancer risk. Future studies are needed to replicate these findings. This trial was registered at clininicaltrials.gov as NCT00342992.

HGF/Met Signaling in Head and Neck Cancer: Impact on the Tumor Microenvironment.

Studies to date have revealed several major molecular alterations that contribute to head and neck squamous cell carcinoma (HNSCC) initiation, progression, metastatic spread, and therapeutic failure. The EGFR is the only FDA-approved therapeutic target, yet responses to cetuximab have been limited. Activation and cross-talk of cellular receptors and consequent activation of different signaling pathways contribute to limited activity of blockade of a single pathway. The hepatocyte growth factor (HGF) receptor, Met, has been implicated in HNSCC tumorigenesis and EGFR inhibitor resistance. HGF, the sole ligand of Met, is overexpressed in the tumor microenvironment. The role of HGF/Met signaling in proliferation, metastasis, and angiogenesis has been investigated in HNSCC, leading to clinical trials with various Met inhibitors and HGF antibodies. However, the role of the HGF/Met signaling axis in mediating the tumor microenvironment has been relatively understudied in HNSCC. In this review, we discuss the functional roles of Met and HGF in HNSCC with a focus on the tumor microenvironment and the immune system. Clin Cancer Res; 22(16); 4005-13. ©2016 AACR.

Toenail selenium status and risk of subtypes of head-neck cancer: The Netherlands Cohort Study.

BACKGROUND: There is limited prospective data on the relationship between selenium status and the risk of head-neck cancer (HNC) and HNC subtypes (i.e., oral cavity cancer [OCC], oro-/hypopharyngeal cancer [OHPC] and laryngeal cancer [LC]). Therefore, we investigated the association between toenail selenium, reflecting long-term selenium exposure, and HNC risk within the Netherlands Cohort Study. METHODS: At baseline, 120,852 participants completed a self-administered questionnaire about diet and other cancer risk factors and were asked to provide toenail clippings. After 20.3 years of follow-up, 294 cases of HNC (95 OCC, 62 OHPC, two oral cavity/pharynx unspecified or overlapping and 135 LC) and 2,164 subcohort members were available for case-cohort analysis using Cox proportional hazards models. RESULTS: Toenail selenium status was statistically significantly associated with a decreased risk of HNC overall (multivariate RR for quartile four versus one: 0.55, 95% confidence interval [CI] 0.37-0.82, P trend = 0.001). The association between toenail selenium and risk of HNC overall was stronger among men than women, but no statistically significant interaction with sex was found. Toenail selenium level was also associated with a decreased risk of all HNC subtypes, with statistically significant associations in OHPC and LC. No statistically significant interaction was found between toenail selenium level and cigarette smoking or alcohol consumption for HNC overall. CONCLUSIONS: In this large cohort study, we found an inverse association between toenail selenium level and HNC risk. Among HNC subtypes, this association was strongest for OHPC and LC. Furthermore, the association of toenail selenium status with HNC risk was stronger among men than women.

Socio Demographic Predictors in Delayed Presentation of Head and Neck Cancer.

Background Head and neck cancer is a major public health problem worldwide. In spite of the increase in incidence, there has been paucity of research on socio demographic factors influencing head and neck cancer. Objective To study the influence of various socio demographic factors on late presentation of head and neck cancer. Method Prospective, analytical study conducted in 69 patients with Head and neck malignancies in Department of Otorhinolaryngology and Head and Neck surgery, Kathmandu University School of Medical sciences between January 2015 to January 2016. Collected data were entered and analyzed using IBM SPSS statistical software 21.0. All the socio demographic variables were compared between the early and late presentation groups of patient using Chi-square test. A 'p' value of < 0.05 was considered statistically significant. Result Forty eight were male and 21 were female. The age of patients ranged from 34 to 70 years (mean age 52.03). Twenty patients were diagnosed in stage I, 13 in stage II, 20 in stage III and 16 in stage IV. Significant association was seen between stage of head and neck cancer and duration of illness (p=0.007), educational status of patient (p=0.003) and educational status of patient's care taker (p=0.005). However, no statistical association was seen between stage at diagnosis of head and neck cancer and gender, type of family, previous consultation, systems of alternative medicine adopted before diagnosis, smoking habit, alcohol intake, tobacco chewing habit and occupation. Conclusion The results of this study suggest that educational status may influence the presentation of head and neck cancer.

In vitro and in vivo inhibition of human Fanconi anemia head and neck squamous carcinoma by a phytonutrient combination.

Head and neck squamous cell carcinoma (HNSCC) and acute myeloid leukemia are the major causes of mortality and morbidity in Fanconi anemia (FA) patients. The objective of this study was to investigate the antineoplastic activity of PB, an antineoplastic nutrient mixture (containing quercetin, curcumin, green tea, cruciferex and resveratrol) on human FA HNSCC in vitro and in vivo. Human FA HNSCC cell line OHSU-974 (Fanconi Anemia Research Fund) was cultured in RPMI medium supplemented with 20% FBS and anti-biotics. At near confluence, cells were treated in triplicate with different concentrations of PB: 0, 10, 25, 50, 75 and 100 µg/ml. Cells were also treated with PMA to induce MMP-9 activity. Cell proliferation was detected by MTT assay, secretion of MMPs by gelatinase zymography, invasion through Matrigel, migration by scratch test and morphology by hematoxylin and eosin (H&E) staining. In vivo, athymic male nude mice (n=12) were inoculated with 3x106 OHSU-974 cells subcutaneously and randomly divided into two groups: group A was fed a regular diet and group B a regular diet supplemented with 1% PB. Four weeks later, the mice were sacrificed and their tumors were excised, weighed and processed for histology. NM inhibited the growth of OHSU-974 tumor by 67.6% (p<0.0001) and tumor burden by 63.6% (p<0.0001). PB demonstrated dose-dependent inhibition of cell proliferation, with 27% (p=0.0003) and 48% (p=0.0004) toxicity at 75 and 100 µg/ml, respectively. Zymography revealed MMP-2 and PMA-induced MMP-9 secretion. PB suppressed secretion of both MMPs in a dose-dependent manner, with total block of both at 50 µg/ml. PB inhibited cell migration (by scratch test) and OHSU-974 invasion through Matrigel in a dose-dependent fashion with total block at 50 µg/ml. H&E staining showed no morphological changes below 50 µg/ml. The results suggest that PB has potential therapeutic use in the treatment of human FA HNSCC.

Trace metals and total antioxidant potential in head and neck cancer patients.

BACKGROUND/OBJECTIVE: There are pieces of evidence suggesting that oxidative stress and immune responses play significant roles in the etiopathogenesis of some malignant diseases. Also increased oxidative stress in patients with certain cancer may result from changes in the levels of certain trace elements. Therefore antioxidants either in the form of trace metals or enzymes are important tools in the study of these conditions. This study aimed at measuring the level of oxidative stress in the head and neck cancer patients by using plasma total antioxidant potential and the plasma level of some antioxidant trace metals. MATERIALS AND METHODS: Twenty cases of head and neck squamous cell carcinoma recruited from the Oral and Maxillofacial surgery and Radiotherapy clinics of the University College Hospital, Ibadan were included in the study. While total antioxidant status was measured by ferric reducing antioxidant power (FRAP) assay of Benzie and Strain (1996), the plasma trace metals were assayed by atomic absorption spectrophotometry. RESULT: The total antioxidant potential was significantly reduced in the study group when compared with controls. Zinc, iron, and selenium were also found to be significantly lower in the study group compared with controls. CONCLUSION: The result suggests a state of oxidative stress in the head and neck cancer patients with likely impact on disease process and treatment outcome.

TGF-ß and NF-κB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers.

Transforming growth factor-beta (TGF-ß) has a dual role in epithelial malignancies, including head and neck squamous cell carcinoma (HNSCC). Attenuation of canonical TGF-ß signaling enhances de novo tumor development, whereas TGF-ß overexpression and signaling paradoxically promotes malignant progression. We recently observed that TGF-ß-induced growth arrest response is attenuated, in association with aberrant activation of nuclear factor-κB (NF-κB), a transcription factor, which promotes malignant progression in HNSCC. However, what role cross-talk between components of the TGF-ß and NF-κB pathways plays in altered activation of these pathways has not been established. Here, we show TGF-ß receptor II and TGF-ß-activated kinase 1 (TAK1) are predominantly expressed in a subset of HNSCC tumors with nuclear activation of NF-κB family member RELA (p65). Further, TGF-ß1 treatment induced sequential phosphorylation of TAK1, IKK, IκBα and RELA in human HNSCC lines. TAK1 enhances TGF-ß-induced NF-κB activation, as TAK1 siRNA knockdown decreased TGF-ß1-induced phosphorylation of IKK, IκB and RELA, degradation of IκBα, RELA nuclear translocation and DNA binding, and NF-κB-induced reporter and target gene transcription. Functionally, TAK1 siRNA inhibited cell proliferation, migration and invasion. Celastrol, a TAK1 inhibitor and anti-inflammatory compound used in traditional Chinese medicine, also decreased TGF-ß1-induced phosphorylation of TAK1 and RELA, and suppressed basal, TGF-ß1- and tumor necrosis factor-alpha (TNF-α)-induced NF-κB reporter gene activity. Celastrol also inhibited cell proliferation, while increasing sub-G0 DNA fragmentation and Annexin V markers of apoptosis. Furthermore, TGF-ß and RELA activation promoted SMAD7 expression. In turn, SMAD7 preferentially suppressed TGF-ß-induced SMAD and NF-κB reporters when compared with constitutive or TNF-α-induced NF-κB reporter gene activation. Thus, cross-talk by TGF-ß via TAK1 and NF-κB promotes the malignant phenotype of HNSCC. Moreover, NF-κB may contribute to the downstream attenuation of canonical TGF-ß signaling through increased SMAD7 expression. Celastrol highlights the therapeutic potential of agents targeting TAK1 as a key node in this pro-oncogenic TGF-ß-NF-κB signal pathway.