Tumors Of Upper Aerodigestive Tract Research Articles

Elective vs. emergency tracheotomy complications in advanced hypopharyngeal cancer.

Squamous cell carcinoma of the hypopharyngeal region is a rare, aggressive disease with a poor prognosis and a high mortality rate, and represents up to 95% of all hypopharyngeal tumors. Patients with upper aerodigestive tract tumors can develop airway compromise before or during chemoradiotherapy. The present study aims to investigate the complication differences between elective tracheostomy and emergency-setting tracheostomy for patients with advanced hypopharyngeal squamous cell. The study group included 36 patients and analyzed the number and type of complications, functional outcomes and comparation of the laboratory testing in all the patients at 3 specific points (before tracheotomy, during the radiation therapy and at least 3 months after completion of radiation therapy). In addition, univariate analysis was performed in order to evaluate the prognosis of local control rates. The type and number of complications between elective and emergency-setting tracheostomy varied, but all the complications were resolved, and no hypoxic complications secondary to displacement of the tracheostomy tube or death cases related to the tracheostomy occurred. A total of 20/36 patients presented with complications, with 73% (16 patients) from the emergency tracheostomy cohort and 36% (4 patients) from the elective tracheostomy group. More than half of the elective tracheostomy (6/11 patients) responded favorably to the treatment, with a higher frequency than the patients with emergency tracheostomy (5/22 patients). The present study did not encounter significant statistical differences (P>0.05) of the treatment end-result regarding the type of tracheostomy performed, but the prediction analysis found for the patients aged under 60 years old, elective tracheostomy was associated with a higher chance of favorable treatment end result.

FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure.

Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis. The F-box and leucine-rich repeat protein 7 (FBXL7) is a potential tumor-suppressing gene, one that is frequently hypermethylated in pancreatic cancer and where the encoded protein promotes the degradation of AURKA, BIRC5 and c-SRC. Thus, the aim of this study was to evaluate the methylation and expression profile of FBXL7 in the UADT and the gene’s association with the clinical, etiological and pathological characteristics of patients, as well as the expression of its degradation targets. Here we show that the FBXL7 gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. FBXL7 body methylation and gene expression levels were correlated in the ESCC, LSCC, OCSCC and OPSCC. Immunohistochemistry analysis showed that FBXL7 protein levels are not correlated with the levels of its degradation targets, AURKA and BIRC5, in the UADT. The high discriminatory potential of FBXL7 body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker.

Peri-Operative Pain and Opioid Use in Opioid-Naïve Patients Following Inpatient Head and Neck Surgery.

Pain management is an important consideration for Head and Neck Cancer (HNC) patients as they are at an increased risk of developing chronic opioid use, which can negatively impact both quality of life and survival outcomes. This retrospective cohort study aimed to evaluate pain, opioid use and opioid prescriptions following HNC surgery. Participants included patients undergoing resection of a head and neck tumor from 2019–2020 at a single academic center with a length of admission (LOA) of at least 24 h. Exclusion criteria were a history of chronic pain, substance-use disorder, inability to tolerate multimodal analgesia or a significant post-operative complication. Subjects were compared by primary surgical site: Neck (neck dissection, thyroidectomy or parotidectomy), Mucosal (resection of tumor of upper aerodigestive tract, excluding oropharynx), Oropharyngeal (OP) and Free flap (FF). Average daily pain and total daily opioid consumption (as morphine milligram equivalents, MME) and quantity of opioids prescribed at discharge were compared. A total of 216 patients met criteria. Pain severity and daily opioid consumption were comparable across groups on post-operative day 1, but both metrics were significantly greater in the OP group on the day prior to discharge (DpDC) (5.6 (1.9–8.6), p < 0.05; 49 ± 44 MME/day, p < 0.01). The quantity of opioids prescribed at discharge was associated with opioid consumption on the DpDC only in the Mucosal and FF groups, which had longer LOA (6–7 days) than the Neck and OP groups (1 day, p < 0.001). Overall, 65% of patients required at least one dose of an opioid on the DpDC, yet 76% of patients received a prescription for an opioid medication at discharge. A longer LOA (aOR = 0.82, 95% CI: 0.63–0.98) and higher Charlson Comorbidity Index (aOR = 0.08, 95% CI: 0.01–0.48) were negatively associated with receiving an opioid prescription at the time of discharge despite no opioid use on the DpDC, respectively. HNC patients, particularly those with shorter LOA, may be prescribed opioids in excess of their post-operative needs, highlighting the need the for improved pain management algorithms in this patient population. Future work aims to use prospective surveys to better define post-operative and outpatient pain and opioid requirements following HNC surgery.

Radiothérapie palliative hypofractionnée dans les cancers localement avancés des voies aéro-digestives supérieures

INTRODUCTION : Les cancers des voies aérodigestives supérieures sont un problème de santé publique. Ils ont causé plus de 400.000 décès en 2020 dont 6% sont survenus en Afrique. De nombreux patients consultent à des stades avancés et le seul traitement palliatif local pouvant être envisagé est la radiothérapie. Sur un volume tumoral très important, elle est souvent délivrée selon un étalement court en mode hypofractionné. MATERIELS ET METHODES : De Juin 2018 à Août 2021, 14 patients ont bénéficié d’une radiothérapie palliative hypofractionnée pour des tumeurs des voies aérodigestives supérieures localement avancées. Tous ont eu une confirmation anatomopathologique de leurs cancers. Les patients avec un statut de performance OMS inférieur ou égal à deux ont bénéficié d’une radiothérapie à la dose 20 à 39 Gy en cinq à 13 fractions. Ceux ayant eu une réponse objective ont bénéficié d’un complément de dose jusqu’à une dose totale équivalente de 70 Gy en fractions de deux Gy. RESULTATS : La tuméfaction cervicale et la détresse respiratoire étaient les symptômes les plus fréquents au diagnostic. Il s’agissait de carcinome épidermoïde chez 64,3% des patients et le site d’origine était l’hypopharynx dans 42,9% des cas. Cinq patients ont présenté une réponse objective locorégionale dont deux ont bénéficié d’un complément de dose. Tous les patients ont présenté une radiodermite grade 1 ou 2 et l’un d’eux a présenté une radiomucite grade 4 nécessitant une hospitalisation. CONCLUSION : La radiothérapie hypofractionnée constitue une approche thérapeutique qui pourrait être proposée aux patients avec des cancers localement avancés des voies aérodigestives supérieures.

Upper Aerodigestive Tract Squamous Cell Carcinomas Show Distinct Overall DNA Methylation Profiles and Different Molecular Mechanisms behind WNT Signaling Disruption.

Simple SummarySquamous cell carcinomas of the upper aerodigestive tract are highly incident, lethal, and share the same epithelial lining of origin, risk factors and genetic alterations. However, their biological and clinical behaviors differ, having an impact on patient survival. This study aimed at identifying the main DNA methylation differences between these tumors, giving an overview of the main genomic regions affected, whether DNA methylation gains or losses are more common, the impact on gene expression and the signaling pathways affected. This knowledge will help identifying potential site-specific biomarkers as well as shedding light on whether epigenetic mechanisms explain, at least in part, the diverse behavior of upper aerodigestive tract tumors.Upper aerodigestive tract (UADT) tumors present different biological behavior and prognosis, suggesting specific molecular mechanisms underlying their development. However, they are rarely considered as single entities (particularly head and neck subsites) and share the most common genetic alterations. Therefore, there is a need for a better understanding of the global DNA methylation differences among UADT tumors. We performed a genome-wide DNA methylation analysis of esophageal (ESCC), laryngeal (LSCC), oral (OSCC) and oropharyngeal (OPSCC) squamous cell carcinomas, and their non-tumor counterparts. The unsupervised analysis showed that non-tumor tissues present markedly distinct DNA methylation profiles, while tumors are highly heterogeneous. Hypomethylation was more frequent in LSCC and OPSCC, while ESCC and OSCC presented mostly hypermethylation, with the latter showing a CpG island overrepresentation. Differentially methylated regions affected genes in 127 signaling pathways, with only 3.1% of these being common among different tumor subsites, but with different genes affected. The WNT signaling pathway, known to be dysregulated in different epithelial tumors, is a frequent hit for DNA methylation and gene expression alterations in ESCC and OPSCC, but mostly for genetic alterations in LSCC and OSCC. UADT tumor subsites present differences in genome-wide methylation regarding their profile, intensity, genomic regions and signaling pathways affected.

HPV 16 in Pathogenesis of Upper Aerodigestive Tract Tumors.

Human papillomavirus (HPV) is the worlds most widely sexually transmitted disease. HPV infection play also an important role in the etiopathogenesis of head and neck cancers, especially oropharynx. In a prospective study of 236 patients with squamous cell carcinoma (SCC) of the upper aerodigestive tract (oral cavity, oropharynx, hypopharynx, and larynx), the incidence of p16 positivity in tumor tissue and its relationship to tumor localization, occurrence of risk factors (smoking, alcohol, and sexual behavior), histopathological findings, and stage of disease were analyzed. Smoking and alcohol abuse were observed in 72% of patients with SCC of the upper aerodigestive tract. Risky sexual behavior was present only in the group of patients with orofaryngeal SCC (42%). Immunohistochemical staining revealed that p16 was present in 20% tumors of upper aerodigestive tract, most frequently in the oropharynx (30%). Patients with p16 positive orofaryngeal SCC were younger, and 94% of these pateints admitted risky sexual behavior. Smoking and regular alcohol consumption were more common in patients with p16 negative SCC of the oropharynx (90%). HPV 16 infection plays a role in the etiopathogenesis of oropharyngeal carcinoma. In other locations of the upper aerodigestive tract, smoking and alcohol abuse are major risk factors. Determination of HPV status in oropharyngeal SCC is an integral part of histopathological examinations. Immunohistochemical detection of p16 protein expression in tumor tissue is considered sufficient to stratify patients into HPV positive/negative groups of oropharyngeal carcinoma. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Esophageal Cancer Patients Have a High Incidence of Severe Periodontitis and Preoperative Dental Care Reduces the Likelihood of Severe Pneumonia after Esophagectomy

Background: Poor oral health is a risk factor for causing upper aerodigestive tract tumors, including esophageal cancer. Our aim was to determine the periodontitis rate in our cohort of esophageal cancer patients. We also analyzed whether preoperative dental examination and care reduces the likelihood of severe pneumonia after esophagectomy. Study Design: Between 2003 and 2014, 529 esophageal cancer patients received esophagectomy at Akita University Hospital. We studied 232 patients who had preoperative dental examinations and care (dental care group) retrospectively and assessed the severity of their periodontitis. The dental care group was compared to 297 patients who did not have preoperative dental care (control group) with respect to the incidence of severe pneumonia after esophagectomy. Results: Ninety-one patients (39.2%) in the dental care group were diagnosed with slight periodontitis and 69 (29.7%) were diagnosed with severe periodontitis. Among all the patients, 69 patients (13.0%) were diagnosed with grade 3B postoperative severe pneumonia. The dental care group had a significantly lower incidence of severe pneumonia than the control group. Moreover, multivariable logistic regression analysis revealed that anastomotic leakage, preoperative dental care, gender and %VC were correlated significantly with the occurrence of postoperative severe pneumonia. Conclusion: Preoperative dental examination and care by a dentist are essential to reduce the likelihood of postoperative severe pneumonia in esophageal cancer patients.

A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer.

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10-10) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Site specific effect of tobacco addiction in upper aerodigestive tract tumors: a retrospective clinicopathological study.

An institutional study was carried out in 102 patients to investigate the site specific effect of addictions, that is, tobacco smoking and tobacco chewing (smokeless), both independently and synergistically in development of malignancies in upper aerodigestive tract through retrograde questionnaire. The histopathologically proven cases were interviewed regarding different forms of addictions followed by clinical examination and investigations for grading (according to Modified Broadmann's method) and TNM staging (according to UICC) according to the tumor site. Statistical analysis was done by Pearson test. Out of all proven cases of cancers, 29.4% were only tobacco chewers (smokeless), 25.5% were only smokers, 42.2% were having both types of tobacco addictions (smoke and smokeless), and only 2.9% were having no addiction. Out of only tobacco chewers (smokeless), 83.3% were of oral cavity cancers, 6.7% were of oro- and hypopharynx and the rest were of others. Among only smokers, 69.2% cases were of laryngeal and oro- and hypopharynx as compared to 11.5% of oral cavity cancers (nearly 6 times). Tobacco (smokeless) chewing is associated with oral cancers whereas tobacco smoking is associated with laryngeal and hypopharyngeal carcinoma. Both smoking and smokeless tobacco act in synergy with each other.

Feasibility and Efficacy of an Addiction Treatment Program in Patients With Upper Aerodigestive Tract Cancer

Background: Continuing to smoke or to drink after the treatment of an upper aerodigestive tract (UADT) cancer is known to worsen the prognosis. We assessed the feasibility and efficacy of an addiction treatment program integrated into the cancer treatment. Method: In four units devoted to UADT tumors, we proposed an addiction treatment to all patients still drinking or smoking at the end of the cancer treatment; the abstinence rate was assessed 6 and 12 months later. Results: One hundred and sixteen patients were included. Among the 73 patients still drinking and/or smoking at the end of the cancer treatment, 46.6% accepted an addiction treatment. In the latter, abstinence rate was increased, 52.2% versus 31.03% ( p = .07) at M12. In patients both drinking and smoking, addiction treatment doubled the rate of abstinence of both products (31% vs. 14%). Conclusion: Offering addiction treatment to patients with UADT cancer improves abstinence rate and helps maintain long-term withdrawal.

HPV in upper aerodigestive tract tumors in southern Brazil.

e15083 Background: The highest rates of esophageal cancer in Brazil occur in Rio Grande do Sul (18/100,000/year for men), where squamous cell carcinoma is the most common. Furthermore, the incidence of head and neck squamous cell carcinoma (HNSCC) is significant in this region (11/100,000/year for cancer of the oral cavity and 10/100,000/year for laryngeal cancer in men). Tobacco smoking and alcohol consumption are the major risk factors for esophageal squamous cell carcinoma (ESCC) and HNSCC. The role of HPV in the development of ESCC remains controversial. Otherwise, there is some evidence that HPV-related HNSCC is a distinct entity compared with HNSCC associated with smoking and alcohol consumption. Methods: Polymerase chain reaction (PCR) was used to evaluate the presence of HPV from 218 samples from three groups of patients. Group 1 comprised 51 patients with ESCC who underwent esophagectomy, in which two samples from each patient were analyzed: one tumor sample and another from normal esophageal mucosa. Group 2 comprised 37 patients with HNSCC who underwent Lugol chromoendoscopy. In this group, we took biopsies from the primary tumor and from esophageal mucosa (unstained areas and middle esophagus when the esophageal mucosa was evenly stained). Thirty-seven dyspeptic patients, non-smokers and without alcohol consumption who underwent endoscopy, comprised Group 3, in which we took one biopsy from middle esophagus. All samples were fixed in formalin and stored in paraffin blocks. Nested-PCR with MY09/11 and GP5/6 primers was used to detect HPV L1 in those samples. Results: Of a total of 224 samples fixed in formalin and stored in paraffin, only 6 samples had insufficient material for PCR analysis: one sample from normal distal epithelium in Group 1, one sample from a stained area and 2 samples from unstained areas in Group 2 and 2 samples from normal esophageal mucosa in Group 3. PCR was positive for one of conserved genes GAPDH, G3PDH or B-globin in 218 samples, showing that DNA was adequate for analysis. The PCR results were negative for HPV DNA in all esophageal samples, as well as in all biopsies from the primary tumor of HNSCC. Conclusions: There is no evidence that HPV is involved in carcinogenesis of the upper aerodigestive tract in southern Brazil.

HPV in upper aerodigestive tract tumors in southern Brazil.

47 Background: The highest rates of esophageal cancer in Brazil occur in Rio Grande do Sul (18/100,000/year for men), where squamous cell carcinoma is the most common. Furthermore, the incidence of head and neck squamous cell carcinoma (HNSCC) is significant in this region (11/100,000/year for cancer of the oral cavity and 10/100,000/year for laryngeal cancer in men). Tobacco smoking and alcohol consumption are the major risk factors for esophageal squamous cell carcinoma (ESCC) and HNSCC. The role of HPV in the development of ESCC remains controversial. Otherwise, there are some evidence that HPV-related HNSCC is a distinct entity compared with HNSCC associated with smoking and alcohol consumption. Methods: Polymerase chain reaction (PCR) was used to evaluate the presence of Human Papillomavirus from 218 samples from three groups of patients. Group 1 comprised 51 patients with ESCC who underwent esophagectomy, in which two samples from each patient were analyzed: one sample of the tumor and another of normal esophageal mucosa distant from the tumor. Group 2 comprised 37 patients with HNSCC who underwent Lugol chromoendoscopy. In this group, samples were analyzed from the primary tumor, the stained areas of mucosa from the middle esophagus, and, when present, discolored and tumoral areas of the esophageal mucosa. Thirty-seven dyspeptic patients, not exposed to smoking or alcohol consumption, comprised Group 3, in which one sample per patient of mucosa with normal appearance from the middle esophagus was evaluated. Nested-PCR with MY09/11 and GP5/6 L1 primers was used to detect HPV L1 in samples fixed in formalin and stored in paraffin blocks. Results: Of a total of 224 samples fixed in formalin and stored in paraffin, only 6 samples had insufficient material for PCR analysis: one sample from normal distal epithelium in Group 1, one sample from a stained area and 2 samples from unstained areas in Group 2 and two samples from normal esophageal mucosa in Group 3. PCR was positive for one of conserved genes GAPDH, G3PDH or B-globin and negative for HPV DNA in all the 118 samples tested. Conclusions: There is no evidence that HPV is involved in carcinogenesis of the upper aerodigestive tract in southern Brazil.

Histopathological spectrum of tumours of upper aero digestive tract in Surat - A study of 156 cases

Background: Cancers of the upper aero-digestive tract (UADT) constitute 3.5-4% of all malignancies. Majority of cases are squamous cell carcinomas which are related with various epidemiologic factors. Aims & Objective: The objective of this study is to know the histopathological spectrum of tumours of UADT. Material and Methods: This study comprises of 156 cases of histopathological diagnosed tumours of upper aero digestive tract who attended new civil hospital, government medical college, Surat, from August 2010 to august 2012. All prospective and neoplastic cases were included and retrospective and non- neoplastic cases were excluded. Routine paraffin sectioning and staining was done and immunohistochemistry was applied when required. Results: Out of total 156 cases of UADT, 129 malignant, 19 cases benign and 8 were carcinoma in-situ cases. In malignant cases, 124 (96.00%) cases of carcinomas, 1 (0.80%) case of sarcoma, 2 (1.60%) cases of melanoma, and 2 (1.60%) cases were of lymphomas. Most common site of carcinoma was oral cavity (tongue). Most common carcinoma was Squamous cell carcinoma. Most common site of SCC was hypo pharynx (pyriform Fossa), followed by oral cavity (tongue) and larynx (supra glottis). In benign tumours, most common site was nasal cavity (7 cases) and common varieties were Angiofibroma and Capillary Haemangioma. Conclusion: Tumours of UADT are predominant in males affecting older age group. People with tobacco chewing, smoking, alcoholism, poor socioeconomic background, mixed diet and poor oral hygiene are more vulnerable.

DNA methylation changes associated with risk factors in tumors of the upper aerodigestive tract

Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.

Fine needle aspiration (FNA) cytology for diagnosis of cervical lymphadenopathy

Patients with cervical adenopathy suspicious for malignancy are often referred to the Otolaryngology Service for tissue diagnosis. Confirmation of nodal involvement by upper aero-digestive tract tumors (UADT) is best obtained by fine needle aspiration (FNA). Reported studies of FNA for lymphoma diagnosis have yielded conflicting results. Retrospective review of charts and pathology of 161 patients diagnosed with lymphomas yielded 53 patients with cervical adenopathy without apparent UADT. FNA's were performed on 28, and were repeated nine times, for a total of 37. Eleven had Hodgkin's disease and 17 other types of lymphomas. Seven of 37 specimens contained only blood; 15 contained lymphoid cells, nine of which were designated "reactive." Lymphoid cells designated as "atypical" or "suspicious for lymphoma" were found in 13 of the 37 aspirates. Two were diagnostic of lymphoma. Lymphoma was confirmed by histopathologic specimens in all patients, obtained 0-941 days (median 15, mean 73 days) after initial FNA. In lymphoma patients with cervical lymphadenopathy, FNA does not usually suffice for, and often leads to significant delays in diagnosis.

Airway management before chemoradiation for advanced head and neck cancer

Patients with upper aerodigestive tract tumors can have development of airway compromise both before and during chemoradiotherapy (CRT). Tracheotomy is the classic method for securing a safe airway, but tumor debulking may also be used. This was a retrospective review of locoregionally advanced tumors of the base of tongue, larynx, or hypopharynx undergoing CRT between 1995 and 2007. Forty-two of the 109 patients presented with signs or symptoms of airway obstruction. Of these, 28 underwent tracheotomy before CRT, and 11 had tumor debulking. Two of the 11 patients who underwent debulking required tracheotomy within 1 year after CRT for persistent edema and fibrosis. Larynx tumors were more likely to require tracheotomy or debulking than other tumors (p = .01). Debulking is a safe and effective alternative to tracheotomy in select patients with tumor-related airway obstruction before CRT. Patients who undergo debulking should be monitored closely for recurrence of airway compromise during and after CRT.

Human papillomavirus–positive basaloid squamous cell carcinomas of the upper aerodigestive tract: a distinct clinicopathologic and molecular subtype of basaloid squamous cell carcinoma

Basaloid squamous cell carcinoma of the upper aerodigestive tract is a rare, morphologically distinct variant of squamous cell carcinoma that is thought to be clinically aggressive. The histologic features are distinct from, but often confused with, those of human papillomavirus-related oropharyngeal nonkeratinizing squamous cell carcinoma. The role of human papillomavirus as an etiologic agent in true basaloid squamous cell carcinoma is controversial. The purpose of this study was to determine human papillomavirus prevalence and its clinicopathologic significance in upper aerodigestive tract tumors with true basaloid squamous cell carcinoma histology. Twenty-eight cases were identified, 12 in the oropharynx and 16 in the larynx and/or hypopharynx. High-risk human papillomavirus in situ hybridization and immunohistochemistry for p16 and p53 were performed. Nine (75%) of the oropharyngeal and none of the larynx/hypopharynx tumors were human papillomavirus positive. Human papillomavirus-positive tumors affected younger patients. No significant statistical differences in patients' sex, tumor stage, treatment modality, or length of follow-up were observed between the 2 groups. Viral status showed a strong, positive correlation with p16 (P < .001) and a strong, negative correlation with p53 (P < .0001) immunoreactivity. Overall survival was better for human papillomavirus-positive basaloid squamous cell carcinomas (P < .05), with 86% of patients alive at 3 years compared with 35.3% of patients with human papillomavirus-negative tumors. These findings suggest that a subset of basaloid squamous cell carcinomas is virally driven. These tumors occur almost exclusively in the oropharynx, are molecularly distinct from their human papillomavirus-negative counterparts, and have a more favorable clinical outcome.

Abstract A207: Whole transcriptome profiling in upper aerodigestive tract cancers

Abstract Background: RNA-seq is a powerful technology that allows to obtain sequence and expression information simultaneously. We applied this technology to 4 upper aerodigestive tract cancers. Methods: RNA from four upper aerodigestive tract tumor specimens was extracted and sequencing libraries constructed. Samples were analyzed using an Illumina Genome Analyzer with a paired end module (36 or 54 base read length). Raw data was processed with a proprietary data pipeline. Potential mutations were filtered using both in house and external bioinformatic solutions, involving previously established databases of mutations (COSMIC) and SNPs (dbSNP), and removal of ancestral alleles identified from multiple sequence alignments. These SNPs were then parsed via in house scripts to determine whether the SNPs were present in coding regions, 3′UTR, 5′UTR, or in splice acceptor/donor sites. The coding SNPs were further parsed to determine which SNPs result in non-synonymous changes. RNA-Seq expression data was analyzed using Partek Genomics Suite and compared to microarray based expression data. Pathway analysis was performed using GeneGO Metacore and DAVID. Results: 500Mb to 2GB of data were obtained per sample. Between 700 and 2000 nsSNPs were identified, as well as a large number of alteration in the 3′ and 5′ untranslated regions. Genetic alterations in several commonly mutated genes were identified including TP53, ErbB2, H-RAS, and Cyclin D1. SNPs were enriched in pathways commonly involved in upper aerodigestive tract tumors including cell cycle control, cytoskeleton, and receptor tyrosine kinases. Furthermore we screened for viral sequences identifying one sample that was HPV16 positive. RNA-seq based and microarray based expression data generally correlated, but significant differences were also observed, that were at least partly due to the limited number of RNA-seq reads. Conclusion: Cancer transcriptome sequencing is a promising and cost effective approach for identifying mutations and obtaining expression analysis simultaneously. Transcriptome sequencing holds promise as a readily available platform for assessing potential treatment targets in a specific tumor. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A207.

Quantitative expression and immunogenicity of MAGE‐3 and ‐6 in upper aerodigestive tract cancer

The MAGE antigens are frequently expressed cancer vaccine targets. However, quantitative analysis of MAGE expression in upper aerodigestive tract (UADT) tumor cells and its association with T-cell recognition has not been performed, hindering the selection of appropriate candidates for MAGE-specific immunotherapy. Using quantitative RT-PCR (QRT-PCR), we evaluated the expression of MAGE-3/6 in 65 UADT cancers, 48 normal samples from tumor matched sites and 7 HLA-A*0201+ squamous cell carcinoma of the head and neck (SCCHN) cell lines. Expression results were confirmed using Western blot. HLA-A*0201:MAGE-3- (271-279) specific cytotoxic T lymphocytes (MAGE-CTL) from SCCHN patients and healthy donors showed that MAGE-3/6 expression was highly associated with CTL recognition in vitro. On the basis of the MAGE-3/6 expression, we could identify 31 (47%) of the 65 UADT tumors, which appeared to express MAGE-3/6 at levels that correlated with efficient CTL recognition. To confirm that the level of MAGE-3 expression was responsible for CTL recognition, 2 MAGE-3/6 mRNA(high) SCCHN cell lines, PCI-13 and PCI-30, were subjected to MAGE-3/6-specific knockdown. RNAi-transfected cells showed that MAGE expression and MAGE-CTL recognition were significantly reduced. Furthermore, treatment of cells expressing low MAGE-3/6 mRNA with a demethylating agent, 5-aza-2'-deoxycytidine (DAC), increased the expression of MAGE-3/6 and CTL recognition. Thus, using QRT-PCR UADT cancers frequently express MAGE-3/6 at levels sufficient for CTL recognition, supporting the use of a QRT-PCR-based assay for the selection of candidates likely to respond to MAGE-3/6 immunotherapy. Demethylating agents could increase the number of patients amenable for targeting epigenetically modified tumor antigens in vaccine trials.

Carcinoma de células escamosas da hipofaringe em mulher jovem com anemia de Fanconi

A anemia de Fanconi é um raro distúrbio autossômico recessivo caracterizado por malformações congênitas, aplasia da medula óssea e instabilidade genômica, com predisposição ao desenvolvimento de neoplasias malignas, em especial as leucemias e os tumores do trato aerodigestivo alto. Em razão de características inerentes à síndrome em questão, o tratamento de tais neoplasias é particularmente difícil. Relata-se o caso de anemia de Fanconi uma jovem de 24 anos, que desenvolveu carcinoma de células escamosas da hipofaringe, na ausência de fatores de risco como o tabagismo e o alcoolismo, e faz-se uma revisão sumária da literatura a respeito do tema.