Salvage total laryngectomy for squamous cell carcinoma of the larynx and hypopharynx: Validated prognostic nomograms predicting oncological outcomes.

BACKGROUND: Salvage total laryngectomy (STL) is a preferred treatment for patients with residual, recurrent, and second primary squamous cell carcinoma of the larynx/hypopharynx after (chemo)radiation. To individually estimate postoperative oncological outcomes, we designed and validated prognostic nomograms. METHODS: We used a dataset of 290 patients who underwent STL. Nomograms predicting 2- and 5-year OS, DFS, and DSS were developed, using variables which are identified pre- or postoperatively. The nomograms were externally validated on a dataset of 109 patients. RESULTS: The nomograms based on postoperative variables performed better than those based on preoperative variables (OS: C = 0.68 vs. 0.64; DFS: C = 0.70 vs. 0.64; DSS: C = 0.74 vs. 0.64). The nomogram predicting DSS based on postoperative variables performed best. CONCLUSIONS: The presented prognostic nomograms for predicting oncological outcomes in patients who undergo STL are tools which allow for a reliable prognostic assessment.

Bile reflux and hypopharyngeal cancer (Review).

Laryngopharyngeal reflux, a variant of gastroesophageal reflux disease, has been considered a risk factor in the development of hypopharyngeal cancer. Bile acids are frequently present in the gastroesophageal refluxate and their effect has been associated with inflammatory and neoplastic changes in the upper aerodigestive tract. Recent in vitro and in vivo studies have provided direct evidence of the role of acidic bile refluxate in hypopharyngeal carcinogenesis and documented the crucial role of NF­κB as a key mediator of early oncogenic molecular events in this process and also suggested a contribution of STAT3. Acidic bile can cause premalignant changes and invasive squamous cell cancer in the affected hypopharynx accompanied by DNA damage, elevated p53 expression and oncogenic mRNA and microRNA alterations, previously linked to head and neck cancer. Weakly acidic bile can also increase the risk for hypopharyngeal carcinogenesis by inducing DNA damage, exerting anti­apoptotic effects and causing precancerous lesions. The most important findings that strongly support bile reflux as an independent risk factor for hypopharyngeal cancer are presented in the current review and the underlying mechanisms are provided.

Nursing Observation on the Clinical Efficacy and Toxicity of Lobaplatin Compared with Cisplatin in the Treatment of Locally Advanced Hypopharyngeal Carcinoma Based on Intelligent CT Imaging.

With the acceleration of people's life rhythm, the incidence of hypopharyngeal cancer has generally increased. This study mainly explores the clinical efficacy and toxicity of lobaplatin compared with cisplatin in the treatment of locally advanced hypopharyngeal carcinoma based on intelligent CT imaging. Group A received lobaplatin combined with docetaxel induction chemotherapy for 2 cycles after cisplatin combined with intensity-modulated radiotherapy. Lobaplatin was added to the patient, then, 200 ml of 5% glucose was added, and the patient was injected intravenously for 1.8 hours. After 2 cycles of induction chemotherapy, simultaneous lobaplatin chemotherapy was performed every week for 5 weeks (10 mg/week), and the efficacy was evaluated after 4 consecutive courses of treatment. Group B received cisplatin combined with docetaxel induction chemotherapy after 2 cycles of cisplatin combined with intensity-modulated radiotherapy. Group C was the control group and was not treated with cisplatin or docetaxel. Stomach protection treatment was given in time throughout the treatment process. All patients underwent normal CT (NCCT) and enhanced CT (CECT) examinations before treatment. We extracted 5 mm plain scan CTQNCCT and enhanced CT (CECT) digital DICOM images from the PACS system for omics feature selection. Toxic and side effects are rated in different degrees according to the evaluation criteria of the National Cancer Institute (NCD) common adverse events. Blood routine and liver and kidney function tests were checked every week, and the medication was stopped immediately if there is a serious reaction. In addition, in vitro cell culture was set up to test the inhibitory effect of cisplatin and lobaplatin on the proliferation of cancer cells. The incidence of digestive tract reaction was 13.0% in the A plan group and 58.3% in the B plan group. The A group was lower than the B group, and the difference was statistically significant (P=0.001 < 0.05). Compared with cisplatin, lobaplatin has a milder gastrointestinal reaction, and there is no common hepatic and renal toxicity of cisplatin. This study is helpful to provide guidance for the clinical efficacy of locally advanced hypopharyngeal cancer treatment.

Firefighter occupation is associated with increased risk for laryngeal and hypopharyngeal squamous cell carcinoma among men from the Greater Boston area.

OBJECTIVE: Firefighters are exposed to a wide variety of carcinogens during the line of duty, including several associated with head and neck cancer. Existing studies assessing head and neck cancer risk with firefighting have predominately included occupational cohorts or registry data, which are limited by inability to adjust for smoking and alcohol consumption-major risk factors for head and neck cancer. Our objective was to assess the risk of head and neck cancer among men with an occupational history as a firefighter. METHODS: This work was conducted using male subjects from a large population-based case-control study of head and neck cancer from the greater Boston area using self-reported occupational history (718 cases and 905 controls). RESULTS: An occupational history as a firefighter was reported for 11 cases and 14 controls. Although no significant association was observed overall, we observed substantial increased risk for hypopharyngeal and laryngeal squamous cell carcinoma among professional municipal firefighters who had a light or no smoking history (OR=8.06, 95% CI 1.74 to 37.41), with significantly increasing risk per decade as a firefighter (OR=2.10, 95% CI 1.06 to 4.14). CONCLUSION: Professional municipal firefighters may be at increased risk for hypopharyngeal and laryngeal squamous cell carcinoma due to carcinogenic exposures encountered during the line of duty.

Different responses to nivolumab therapy between primary and metastatic tumors in a patient with recurrent hypopharyngeal squamous cell carcinoma.

We report the case of a 70-year-old man with primary and metastatic tumors, showing clinically progressive disease and complete response to nivolumab therapy, respectively. He underwent total pharyngo-laryngectomy, bilateral neck dissection, and reconstruction with free-jejunum after nivolumab therapy failure, and had no recurrent or newly arising lesions 8 months after the surgery. Immunohistochemistry analysis revealed that metastatic neck tumor with the clinical complete response to nivolumab showed higher PD-L1 expression with higher CD8+ TIL density, while primary lesion with progressive disease showed lower PD-L1 expression with lower CD8+ TIL density. This represents the first case reported on head and neck squamous cell carcinoma treated with salvage surgery after nivolumab therapy failure.

Human papillomavirus-associated squamous cell carcinoma of the larynx or hypopharynx: Clinical outcomes and implications for laryngeal preservation.

OBJECTIVES: Human papillomavirus (HPV) can be detected in approximately 25% of squamous cell carcinomas (SCC) of the larynx and hypopharynx. Though HPV is associated with improved survival and disease control in patients with oropharyngeal SCC, the role of HPV as a marker of favorable treatment outcomes in laryngeal and hypopharyngeal cancer is unclear. MATERIALS AND METHODS: Patients treated for laryngeal or hypopharyngeal SCC were reviewed. HPV status detected by p16 and/or HPV DNA PCR were abstracted from the medical record. A subset of samples (stage III-IV treated with primary radiotherapy) was retrospectively tested for p16 and HPV DNA. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were determined and compared between HPV-positive (p16+, PCR+ or both) and HPV-negative (p16- or PCR-) patients. RESULTS: In total, 279 patients were identified, 94 of which were tested for HPV. Eighty-two (87%) were negative and 12 (13%) were positive for HPV. At 3 years, there were no significant differences in OS (72% v. 83%), DFS (60% v. 71%) and LRC (80% v. 89%). Performance status, smoking history and stage predicted for OS, while performance status and stage predicted for DFS. Analysis of patients treated with primary radiotherapy revealed non-significantly higher rates of laryngeal preservation at 3 years (75% v. 100%). CONCLUSION: HPV was detected in 13% of tested laryngeal/hypopharyngeal cancers. HPV does not appear to significantly impact survival or disease control in patients with SCC of the larynx or hypopharynx. Non-significant improvements in laryngeal preservation were observed in HPV-positive patients.

Hypopharyngeal cancer risk in Japanese: Genetic polymorphisms related to the metabolism of alcohol- and tobacco-associated carcinogens.

BACKGROUND: Several studies have investigated hypopharyngeal cancer (HC) risk in combination with xenobiotic metabolism-related genetic polymorphisms and the burden of alcohol consumption and smoking in European countries but not in East Asian countries. PATIENTS AND METHODS: This hospital-based case-control study involved 61 male patients with HC and 71 male cancer-free controls. Information on age, body mass index, and alcohol and cigarette consumption was obtained from medical records, a self-completion questionnaire, and a thorough interview by an otolaryngologist. Alcohol dehydrogenase 1B (ADH1B), aldehyde dehydrogenase 2 (ALDH2), cytochrome P450 A1 (CYP1A1) MspI, CYP1A1 Ile462Val, glutathione S-transferase (GST) M1, GSTT1, and GSTP1 gene polymorphisms were determined by polymerase chain reaction-based methods. Univariate and multivariate analyses were performed by adjustment for age by the Mantel-Haenszel method. RESULTS: The burden of alcohol and cigarette consumption significantly increased the risk of HC and showed a synergistic effect. ADH1B*1/*1 (odds ratio [OR] 7.34) and ALDH2 *1/*2 (OR 13.22) were significant risk factors for HC. Individuals with ADH1B*1/*1 or ALDH2 *1/*2 who consumed alcohol were more susceptible to HC. However, polymorphisms of CYP1A1 gene and GSTs were not significant cancer risk factors in patients with HC. CONCLUSIONS: ADH1B*1/*1 and ALDH2 *1/*2 were significant risk factors for HC, while polymorphism of CYP1A1 gene and GSTs was not a significant risk factor for HC. These polymorphisms determined the effects of alcohol and cigarette smoke in addition to burden of alcohol and cigarettes intake on the risk of HC.

Epidemiology of Hypopharyngeal Cancer.

Hypopharyngeal cancer is uncommon in the developed world; it is mostly diagnosed in men who smoke tobacco and consume excessive alcohol and uncommon in women. However, recent trends in the developed world show that there has been an annual increase in the percentage of women with hypopharyngeal cancer. In France, there has been a significant annual percentage change in the incidence of this form of cancer - a decrease in men and a greater increase in women since the 1980s. In the developing world, India, Taiwan and other countries, the incidence of hypopharyngeal cancer has increased in both men and women. These populations indulge widely in the social habit of tobacco usage at an earlier age, both smoking and chewing, excessive alcohol drinking, along with the chewing of the areca nut. Recent research has proven that areca nut alone is carcinogenic. The combination of tobacco and alcohol has a greater multiplicative impact on increasing the risk of cancer, while the involvement of areca nut remains to be proven. The World Health Organisation has commenced a Global Mission on the cessation of smoking and reduction of alcohol intake. The effect of this work has been credited with a reduction of hypopharyngeal and other head and neck cancers. While the younger aged should be the targeted population to avoid tobacco usage, the middle and older age of the population must be targeted for quitting smoking tobacco.

Hypopharyngeal Skin Cancer Following Total Laryngectomy and Pectoralis Flap Reconstruction: Case Report and Literature Review.

Although early complications of microvascular free flaps and regional pedicled flaps of the head and neck are well described in the literature, there is relatively limited knowledge regarding their long-term complications. We describe the case of a 62-year-old gentleman who underwent primary resection and adjuvant radiation therapy for supraglottic squamous cell carcinoma who subsequently underwent salvage total laryngectomy with pectoralis major muscle flap reconstruction. During a later esophageal dilation for complaints of dysphagia, a new exophytic lesion of the hypopharynx was biopsied on endoscopy. The lesion was excised via transoral robotic surgery with final pathology revealing squamous cell carcinoma completely confined to the skin paddle of the pectoralis flap and arising from the epidermis of the skin flap. No further therapy was undertaken and there has been no evidence of recurrence 2 years after resection. Synchronous cutaneous malignancy is a rare complication of free and pedicled flap reconstruction, however its diagnosis is increasing. Given the concern for recurrent mucosal tumors arising in the upper aerodigestive tract which may require extensive resection with or without adjuvant therapy, it is important to determine the etiology of the underlying malignancy to guide appropriate treatment.

Hypopharyngeal carcinoma: Do you know your guidelines?

BACKGROUND: Hypopharyngeal carcinoma is relatively rare, representing approximately 3% of all head and neck malignancies. It also is characterized by having one of the worst prognoses at time of diagnosis. This is largely due to its tendency for late presentation. METHODS: This article will review current literature including as well as the National Comprehensive NCCN Guidelines Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of hypopharyngeal cancer. RESULTS: Hypopharyngeal cancer often presents in an advanced stage and its prognosis is notoriously poor. Treatment goals are similar to other carcinomas of the head and neck and treatment typically involves multiple modalities including surgery, radiation, and chemotherapy. Organ sparing nonsurgical therapy has shown comparable survival outcomes to surgery in early stage hypopharyngeal cancer. CONCLUSION: Treating hypopharyngeal cancer remains a challenging prospect for the head and neck oncologist. A multidisciplinary approach is essential due to the necessity of combined therapy treatment protocols. There is opportunity for novel treatments and prospective trials to improve outcomes in hypopharyngeal carcinoma. Disease prevention by targeting environmental risk factors is likely to have the greatest impact in this disease.

Head and neck squamous cell carcinoma in people living with HIV in France.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC), mainly due to smoking, is one of the leading causes of cancer deaths. However, an increasing number of tumors - especially oropharyngeal cancer - are reported in non-smokers in association with the human papillomavirus (HPV). As HIV-infected individuals are particularly at risk of HPV-related disease, we aimed to describe the burden of HNSCC in this population. METHODS: Retrospective chart review of patients from HIV clinics diagnosed with HNSCC between 2004 and 2014. Case patients were defined using the International Classification of Disease for Oncology (3rd edition). Age at HIV diagnosis and time from HIV diagnosis to HNSCC diagnosis were collected. Oropharyngeal cancers were considered as potentially HPV-related cancers, and their prevalence was compared with other HNSCCs over time. RESULTS: The 286 patients enrolled in the study had a median age at HNSCC diagnosis of 52 years; 84% were males and 68% had a history of smoking. The oropharynx was the most frequent site (41%), followed by cancer of the oral cavity (31%), larynx (22%), and hypopharynx (7%). The prevalence (and proportion) of potentially HPV-related cancers increased significantly over time with a mean of 0.78 additional case patient per year. CONCLUSION: The prevalence of HNSCC is modest compared with other cancers in HIV-infected individuals. The prevalence of oropharynx carcinoma, a potentially HPV-related carcinoma, seems to increase over time. Even if tobacco may be an important contributor, the role of HPV in HIV-infected individuals presenting with HNSCC should be investigated.

Occupational exposure to petroleum-based and oxygenated solvents and hypopharyngeal and laryngeal cancer in France: the ICARE study.

BACKGROUND: To examine associations between occupational exposure to petroleum-based and oxygenated solvents and the risk of hypopharyngeal and laryngeal cancer. METHODS: ICARE is a large, frequency-matched population-based case-control study conducted in France. Lifetime occupational history, tobacco smoking and alcohol consumption were collected. Analyses were restricted to men and included 383 cases of hypopharyngeal cancer, 454 cases of laryngeal cancer, and 2780 controls. Job-exposure matrices were used to assess exposure to five petroleum-based solvents (benzene; gasoline; white spirits; diesel, fuels and kerosene; special petroleum products) and to five oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran). Odds ratios (ORs) adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals (CI) were estimated with unconditional logistic models. RESULTS: No significant association was found between hypopharyngeal or laryngeal cancer risk and exposure to the solvents under study. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of white spirits (OR = 1.46; 95% CI: 0.88-2.43) and tetrahydrofuran (OR = 2.63; 95CI%: 0.55-12.65), with some indication of a dose-response relationship (p for trend: 0.09 and 0.07 respectively). CONCLUSION: This study provides weak evidence for an association between hypopharyngeal cancer and exposure to white spirits and tetrahydrofuran, and overall does not suggest a substantial role of exposure to petroleum-based or oxygenated solvents in hypopharyngeal or laryngeal cancer risk.

[Risk factors and survival analysis for synchronous esophageal carcinoma in patients with hypopharyngeal carcinoma].

Objective: To investigate the risk factors and survival status of hypopharyngeal carcinoma with synchronous second primary carcinoma of the esophagus. Methods: One hundred and sixty patients with newly diagnosed hypopharyngeal carcinoma from January 2009 to December 2012 were retrospectively reviewed. The clinical data, tumor-related information and follow-up results were collected and analyzed. Results: Forty-three synchronous esophageal carcinomas (27%) were detected in 160 patients with hypopharyngeal carcinoma, and most patients (72%) were at an early stage. On univariate analysis, the median age of less than 55 years old (χ(2)=4.525, P=0.033), excessive alcohol consumption (χ(2)=6.942, P=0.008) and invasion site more than 3 anatomical regions (χ(2)=21.503, P=0.000) had a significant correlation with the occurrence of synchronous esophageal carcinomas. Multivariate analysis showed that excessive alcohol consumption (OR=4.787, P=0.029) and invasion site more than 3 anatomical regions (OR=14.391, P=0.000) were independent risk factors. The median survival time was 26 months in 43 patients with synchronous esophageal carcinomas, which was significantly lower than that (58 months) in patients without secondary primary esophageal carcinomas (χ(2)=11.981, P=0.001). Conclusions: There is a high incidence of synchronous esophageal carcinoma in hypopharyngeal carcinoma patients, affecting the prognosis of hypopharyngeal carcinoma. Surveillance for esophageal carcinomas in patients with hypopharyngeal carcinoma, especially in excessive alcohol drinkers, is warranted.

Intake of meat and fish and risk of head-neck cancer subtypes in the Netherlands Cohort Study.

PURPOSE: To date, the role of meat and fish intake in head-neck cancer (HNC) etiology is not well understood and prospective evidence is limited. This prompted us to study the association between meat, fish, and HNC subtypes, i.e., oral cavity cancer (OCC), oro- and hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), within the Netherlands Cohort Study (NLCS). METHODS: In 1986, 120,852 participants (aged 55-69 years) completed a baseline 150-item food frequency questionnaire (FFQ), from which daily meat and fish intake were calculated. After 20.3 years of follow-up, 430 HNC overall (134 OCC, 90 OHPC and 203 LC) cases and 4,111 subcohort members were found to be eligible for case-cohort analysis. Multivariate hazard ratios were calculated using Cox's proportional hazards model within quartiles of energy-adjusted meat and fish intake. RESULTS: Processed meat intake, but not red meat intake, was positively associated with HNC overall [HR(Q4 vs. Q1) = 1.46, 95% CI 1.06-2.00; ptrend = 0.03]. Among HNC subtypes, processed meat was positively associated with OCC, while no associations were found with OHPC and LC. Fish intake was not associated with HNC risk. Tests for interaction did not reveal statistically significant interaction between meat, fish, and alcohol or smoking on HNC overall risk. CONCLUSIONS: In this large cohort study, processed meat intake was positively associated with HNC overall and HNC subtype OCC, but not with OHPC and LC.

Bile acids: a potential role in the pathogenesis of pharyngeal malignancy.

OBJECTIVE: Gastro-oesophageal reflux disease is thought to be a risk factor for head and neck malignancies. Bile acids are one of the principle components of gastric refluxate and have previously been implicated in the development of oesophageal and bowel malignancies. There is clear evidence that bile acids reflux into the laryngopharynx. Despite this, the carcinogenic properties of bile acids in this area are yet to be fully identified. We therefore investigated the potential role of bile acids in pharyngeal malignancy, through the highly conserved process of epithelial-mesenchymal transition (EMT). EMT occurs in invasion and metastasis and is a central process in the development of epithelial carcinoma. DESIGN: Translational research study. METHODS: Human hypopharyngeal squamous carcinoma FaDu cells were challenged with primary (cholic or chenodeoxycholic) and secondary (deoxycholic or lithocholic) bile acids. EMT-relevant proteins TGF-ß1 and MMP-9 were measured in the cell culture supernates at 48 h via ELISA. Cell viability was confirmed >95% via CellTiter-Blue assay. RESULTS: Significantly greater concentrations of TGF-ß1 were measured in the culture supernates of cells treated with cholic acid, deoxycholic acid and chenodeoxycholic acid. MMP-9 levels were increased in deoxycholic acid and lithocolic acid stimulations when compared to control (P < 0.05). CONCLUSION: This is the first demonstration that bile acids induce TGF-ß1 and MMP-9 in pharyngeal cells. TGF-ß1 is considered a master switch for EMT, while MMP-9 is a part of the EMT proteome which degrades basement membranes. This implies a potential role for bile acids in pharyngeal carcinogenesis through the mechanism of EMT and suggests potential novel therapeutic targets.

Secondary Neoplasms in Children with Hodgkin's Lymphoma Receiving C-MOPP and Radiotherapy: Presentation of Four Cases.

Patients who survive Hodgkin lymphoma (HL) are at increased risk of secondary neoplasms (SNs). A wide variety of SNs have been reported, including leukemias, non-Hodgkin's lymphomas, and solid tumors, specifically breast and thyroid cancers. Herein we report subsequent neoplasms in four patients with HL receiving chemoradiotherapy. It is interesting that three SNs, fibrosarcoma, thyroid carcinoma, and retrobulbar meningioma, were observed in the radiation area in one of our patients. A hypopharyngeal epithelioid malignant peripheral nerve sheath tumor as an unusual secondary malignant neoplasm developed in another patient, while a benign thyroid nodule and invasive ductal breast carcinoma were observed at different times in the female patient. Follicular adenoma of the thyroid gland developed in one of our patients.

Alcohol consumption, cigarette smoking and the risk of subtypes of head-neck cancer: results from the Netherlands Cohort Study.

BACKGROUND: Prospective data on alcohol consumption, cigarette smoking and risk of head-neck cancer (HNC) subtypes, i.e. oral cavity cancer (OCC), oro-/hypopharyngeal cancer (OHPC), and laryngeal cancer (LC), are limited. We investigated these associations within the second largest prospective study on this topic so far, the Netherlands Cohort Study. METHODS: 120,852 participants completed a questionnaire on diet and other cancer risk factors in 1986. After 17.3 years of follow-up, 395 HNC (110 OCC, 83 OHPC, and 199 LC) cases and 4288 subcohort members were available for case-cohort analysis using Cox proportional hazards models. RESULTS: For total HNC, the multivariable adjusted incidence rate ratio (RR) was 2.74 (95% confidence interval (CI) 1.85-4.06) for those drinking ≥30 g ethanol/day compared with abstainers; in subtypes, RRs were 6.39 for OCC, 3.52 for OHPC, and 1.54 for LC. Compared with never cigarette smokers, current cigarette smokers had a RR of 4.49 (95%CI 3.11-6.48) for HNC overall, and 2.11 for OCC, 8.53 for OHPC, and 8.07 for LC. A significant, positive, multiplicative interaction between categories of alcohol consumption and cigarette smoking was found for HNC overall (P interaction 0.03). CONCLUSIONS: Alcohol consumption and cigarette smoking were independently associated with risk of HNC overall, with a positive, multiplicative interaction. The strength of these associations differed among HNC-subtypes: OCC was most strongly associated with alcohol consumption but most weakly with cigarette smoking, whereas LC was not statistically significantly associated with alcohol consumption.

Chronic pepsin exposure promotes anchorage-independent growth and migration of a hypopharyngeal squamous cell line.

OUTCOME OBJECTIVES: (1) Investigate the role of reflux, specifically pepsin, in laryngopharyngeal carcinogenesis. (2) Evaluate effects of chronic pepsin exposure on cell migration, apoptosis, and colony-forming ability in hypopharyngeal cells. STUDY DESIGN: Translation research. SETTING: Academic research laboratory. METHODS: Human hypopharyngeal squamous carcinoma FaDu cells were chronically exposed to nonacidic pepsin (exposed for 24 hours, 4 times over 2 weeks at the following concentrations: 0.01 mg/mL, 0.1 mg/mL, or 1 mg/mL). Precise wounds were created in confluent cell plates, and rates of cell migration into wounds were quantified. Separately, cell viability of chronic pepsin-exposed FaDu cells acutely treated with paclitaxel was measured. Finally, a clonogenic assay was performed on these cells to measure effects of chronic pepsin exposure on colony-forming ability. RESULTS: An increased rate of relative wound density was observed in chronic pepsin-treated (0.01 mg/mL, 0.1 mg/mL) cells compared with control (P < .001), suggesting greater rates of cell migration. Pepsin-treated (0.1 mg/mL) cells demonstrated on average greater cell viability compared with control after exposure to paclitaxel, suggesting possible apoptotic resistance; however, this was not statistically significant. Chronic pepsin exposure (0.1 mg/mL, 1 mg/mL) was associated with a dose-dependent increase in colony-forming ability relative to control (P < .001). CONCLUSION: Hypopharyngeal squamous cell line chronically exposed to pepsin demonstrated increased cell migration and colony-forming ability relative to control cells. These experiments indicate that chronic pepsin exposure acts as a promoter of tumorigenesis and metastasis of airway epithelium, suggesting a role for pepsin in laryngopharyngeal carcinogenesis attributed to gastric reflux.

Associations of tobacco use and alcohol drinking with laryngeal and hypopharyngeal cancer risks among men in Karunagappally, Kerala, India -Karunagappally cohort study.

BACKGROUND: From among a cohort of 65,553 men aged 30-84 in Karunagappally Taluk, Kerala, India, 52 hypopharyngeal cancer cases and 85 laryngeal cancer cases were identified by the Karunagappally Cancer Registry during the period between 1990 and 2009. METHODS: We conduct Poisson regression analysis of grouped data, taking into account age and education. RESULTS: This study showed that the incidence rates of cancers of the hypopharynx and the larynx were strongly related to the number of bidis smoked a day (P<0.001 for both hypopharyngeal and laryngeal cancers) and duration of bidi smoking (P=0.009; P<0.001). Laryngeal cancer risk was significantly increased by bidi smoking (P<0.001), cigarette smoking (P=0.013) and regular alcohol use (P=0.005). CONCLUSION: The present study, the first cohort study to examine the association of hypopharyngeal and laryngeal cancer incidence rates with bidi smoking in South Asia, clearly showed dose-response relationships between those cancer risks and bidi smoking; larger amounts of bidi smoked a day and longer durations of bidi smoking increased the incidence rates of those cancers. Tobacco chewing was found not related to the risk of hypopharynx or larynx cancer.