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1.
Cancer ; 125(8): 1281-1289, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30645761

RESUMO

BACKGROUND: In the era of deintensification, little data are available regarding patients' treatment preferences. The current study evaluated treatment-related priorities, concerns, and regret among patients with head and neck squamous cell cancer (HNSCC). METHODS: A total of 150 patients with HNSCC ranked the importance of 10 nononcologic treatment goals relative to the oncologic goals of cure and survival. The level of concern regarding 11 issues and decision regret was recorded. Median rank was reported overall, and factors associated with odds of rank as a top 3 priority were modeled using logistic regression. RESULTS: Among the treatment effects analyzed, the odds of being a top 3 priority was especially high for cure (odds, 9.17; 95% confidence interval [95% CI], 5.05-16.63), followed by survival and swallow (odds, 1.26 [95% CI, 0.88-1.80] and odds, 0.85 [95% CI, 0.59-1.21], respectively). Prioritization of cure, survival, and swallow was similar based on human papillomavirus (HPV) tumor status. By increasing decade of age, older participants were found to be significantly less likely than younger individuals to prioritize survival (odds ratio, 0.72; 95% CI, 0.52-1.00). Concerns regarding mortality (P = .04) and transmission of HPV to the patient's spouse (P = .03) were more frequent among participants with HPV-associated HNSCC. Regret increased with additional treatment modalities (P = .02). CONCLUSIONS: Patients with HNSCC overwhelming prioritize cure, followed by survival and swallow. The decreased prioritization of survival by older age supports further examination of treatment preference by age. The precedence of oncologic over nononcologic priorities among patients regardless of HPV tumor status supports the conservative adoption of deintensification regimens until the interplay between competing oncologic and nononcologic treatment goals is better understood.


Assuntos
Tomada de Decisões , Neoplasias de Cabeça e Pescoço/terapia , Prioridades em Saúde/classificação , Infecções por Papillomavirus/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Papillomaviridae , Satisfação do Paciente , Assistência Centrada no Paciente , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Análise de Sobrevida , Resultado do Tratamento
2.
Cancer ; 123(10): 1768-1777, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28055120

RESUMO

BACKGROUND: Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) have improved survival when compared with those with HPV-negative OPC. Unfortunately, the American Joint Committee on Cancer seventh edition (AJCC-7ed) staging system does not account for the prognostic advantage observed with HPV-positive OPC. The purpose of the current study was to validate and compare 2 recently proposed staging systems for HPV-positive OPC. METHODS: Patients treated for HPV-positive OPC from 2005 to 2015 at Johns Hopkins Hospital (JHH) were included for analysis. The International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S) and The University of Texas MD Anderson Cancer Center (MDACC) staging systems were applied and survival was calculated using Kaplan-Meier methods. Cox proportional hazard regression was used to determine the relationship between stage of disease and survival. Models were compared using the Akaike information criterion (AIC). RESULTS: A total of 435 patients were eligible for analysis. There was a dramatic shift in lymph node category and overall stage of disease when ICON-S and MDACC stage were applied to the JHH cohort. There was superior stratification of overall survival and progression-free survival by ICON-S stage. Both proposed models had an improved fit based on AIC scores (P<.001 for both) over the AJCC-7ed. The ICON-S staging system had the lowest AIC score, and thus a better fit within the JHH population. CONCLUSIONS: The current analysis provides external validation for both staging systems in an independent and heterogeneously treated patient population. Although the MDACC staging system is an improvement over the AJCC-7ed, the ICON-S stage provides superior stratification of overall and progression-free survival, thereby supporting its use as the updated AJCC staging system for OPC. Cancer 2017;123:1768-1777. © 2017 American Cancer Society.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/patologia , Linfonodos/patologia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/patologia , Idoso , Carcinoma de Células Escamosas/complicações , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Pescoço , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/complicações , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Prognóstico , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Taxa de Sobrevida
3.
Int J Cancer ; 139(2): 373-82, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-26949921

RESUMO

The Cancer Genome Atlas (TCGA) sequencing analysis of head and neck squamous cell carcinoma (HNSCC) recently reported on gene fusions, however, few human papillomavirus (HPV) positive samples were included, and the functional relevance of identified fusions was not explored. We therefore performed an independent analysis of gene fusions in HPV-positive oropharyngeal SCC (OPSCC). RNA sequencing was performed on 47 HPV-positive OPSCC primary tumors and 25 normal mucosal samples from cancer unaffected controls on an Illumina TruSeq platform. MapSplice2 was used for alignment and identification of fusion candidates. Putative fusions with less than five spanning reads, detected in normal tissues, or that mapped to the same gene were filtered out. Selected fusions were validated by RT-PCR and Sanger sequencing. Within 47 HPV-positive OPSCC tumors, 282 gene fusions were identified. Most fusions (85.1%) occurred in a single tumor, and the remaining fusions recurred in 2-16 tumors. Gene fusions were associated with significant up regulation of 16 genes (including EGFR and ERBB4) and down regulation of four genes (PTPRT, ZNF750, DLG2, SLCO5A1). Expression of these genes followed similar patterns of up regulation and down regulation in tumors without these fusions compared to normal tissue. Five of six gene fusions selected for validation were confirmed through RT-PCR and sequencing. This integrative analysis provides a method of prioritizing functionally relevant gene fusions that may be expanded to other tumor types. These results demonstrate that gene fusions may be one mechanism by which functionally relevant genes are altered in HPV-positive OPSCC.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Fusão Gênica , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/etiologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Biomarcadores Tumorais , Análise por Conglomerados , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos
4.
Cancer ; 122(12): 1861-70, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27182694

RESUMO

BACKGROUND: Understanding health-related quality of life (HRQOL) is crucial to providing high-quality survivorship care for patients with head and neck squamous cell carcinoma (HNSCC). Trends in and prognostic significance of HRQOL before and after HNSCC have not been well described. METHODS: HRQOL for older individuals with HNSCC was examined using the linked Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey database. Surveys assessing HRQOL from 5 years prediagnosis to 10 years postdiagnosis were included. HRQOL over time was modeled using multilevel linear regression with restricted cubic splines and was reported as either total HRQOL or change in HRQOL (denoted Δ). The association of prediagnosis HRQOL with survival was examined. RESULTS: In total, 1653 individuals were included; of these, 61% completed 1 survey, and 39% completed multiple surveys. Overall HRQOL decreased progressively until 13 months postdiagnosis, then recovered toward baseline between 2 and 5 years. However, after stratification by survival group, the postdiagnosis recovery was not observed. Individuals with shorter survival had lower HRQOL prediagnosis (<2-year survivors, 87.3; > 5-year survivors, 96.4; P = .004) with a steeper decline in HRQOL during diagnosis and treatment (<2-year survivors: Δ, -16.6; 95% confidence interval [CI], -23.8, -9.4; > 5-year survivors: Δ, -0.9; 95% CI, -1.8, 0.08). Radiotherapy and advanced stage were associated with greater declines in HRQOL during diagnosis and treatment (P < .001). Higher prediagnosis HRQOL was independently associated with improved overall survival (adjusted hazard ratio for 10-point increase, 0.91; 95% CI, 0.85-0.97). CONCLUSIONS: HRQOL declines before and after HNSCC, whereas any observed posttreatment recovery is likely an artifact of shorter survival among individuals with the lowest HRQOL. The prognostic implication of prediagnosis HRQOL may inform patient counseling. Cancer 2016;122:1861-70. © 2016 American Cancer Society.


Assuntos
Carcinoma de Células Escamosas/fisiopatologia , Carcinoma de Células Escamosas/psicologia , Neoplasias de Cabeça e Pescoço/fisiopatologia , Neoplasias de Cabeça e Pescoço/psicologia , Fatores Etários , Idoso , Carcinoma de Células Escamosas/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Masculino , Medicare , Qualidade de Vida , Programa de SEER , Carcinoma de Células Escamosas de Cabeça e Pescoço , Inquéritos e Questionários , Estados Unidos/epidemiologia
5.
Int J Cancer ; 137(8): 1879-89, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25857630

RESUMO

Using high-throughput analyses and the TRANSFAC database, we characterized TF signatures of head and neck squamous cell carcinoma (HNSCC) subgroups by inferential analysis of target gene expression, correcting for the effects of DNA methylation and copy number. Using this discovery pipeline, we determined that human papillomavirus-related (HPV+) and HPV- HNSCC differed significantly based on the activity levels of key TFs including AP1, STATs, NF-κB and p53. Immunohistochemical analysis confirmed that HPV- HNSCC is characterized by co-activated STAT3 and NF-κB pathways and functional studies demonstrate that this phenotype can be effectively targeted with combined anti-NF-κB and anti-STAT therapies. These discoveries correlate strongly with previous findings connecting STATs, NF-κB and AP1 in HNSCC. We identified five top-scoring pair biomarkers from STATs, NF-κB and AP1 pathways that distinguish HPV+ from HPV- HNSCC based on TF activity and validated these biomarkers on TCGA and on independent validation cohorts. We conclude that a novel approach to TF pathway analysis can provide insight into therapeutic targeting of patient subgroup for heterogeneous disease such as HNSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , NF-kappa B/genética , Infecções por Papillomavirus/genética , Fator de Transcrição STAT3/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/virologia , Linhagem Celular Tumoral , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/virologia , Humanos , NF-kappa B/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Infecções por Papillomavirus/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço
6.
Cancer ; 121(12): 1957-65, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25773145

RESUMO

BACKGROUND: Securing negative surgical margins is a critical goal for head and neck surgery. Local recurrence develops even in some patients who have histologically negative surgical margins. Minimal residual tumor cells may lead to locoregional recurrence despite clear histologic margins reported at the time of resection of head and neck squamous cell carcinoma (HNSCC). To identify subclinical residual disease, the authors analyzed deep margin imprint samples collected on 1-layer nitrocellulose sheets. METHODS: Bisulfite-treated DNA samples from 73 eligible patients were amplified by quantitative methylation-specific polymerase chain reaction (QMSP) targeting 6 genes (deleted in colorectal cancer [DCC], endothelin receptor type B [EDNRB], homeobox protein A9 [HOXA9], kinesin family member 1A [KIF1A], nidogen-2 [NID2], and N-methyl D-aspartate receptor subtype 2B [NR2B]). QMSP values were dichotomized as positive or negative. Associations between the QMSP status of deep margin samples and clinical outcomes were evaluated. RESULTS: Two-gene methylation combinations among the genes DCC, EDNRB, and HOXA9 were associated with decreased locoregional recurrence-free survival, recurrence-free survival, and overall survival. The methylated gene combination of EDNRB and HOXA9 in margin imprints was the most powerful predictor of poor locoregional recurrence-free survival (hazard ratio [HR], 3.31; 95% confidence interval [CI], 1.30-8.46; P = .012) independent of standard histologic factors. In addition, methylation of both EDNRB and HOXA9 indicated a trend toward reduced recurrence-free survival (HR, 2.74; 95% CI, 0.90-8.33; P = .075) and reduced OS (HR, 5.78; 95% CI, 0.75-44.7; P = .093) in multivariable analysis. CONCLUSIONS: A panel of gene methylation targets in deep surgical margin imprints provides a potential predictive marker of postoperative locoregional recurrence. Intraoperative use of molecular margin imprint analysis may assist surgeons in obtaining rigorously negative surgical margins and improve the outcome of head and neck surgery.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Metilação de DNA , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/cirurgia , Recidiva Local de Neoplasia/genética , Biomarcadores Tumorais/genética , Estudos de Coortes , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Predisposição Genética para Doença , Humanos , Neoplasia Residual/genética , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço
7.
Hum Genet ; 134(5): 497-507, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25108461

RESUMO

For TP53-mutated head and neck squamous cell carcinomas (HNSCCs), the codon and specific amino acid sequence change resulting from a patient's mutation can be prognostic. Thus, developing a framework to predict patient survival for specific mutations in TP53 would be valuable. There are many bioinformatics and functional methods for predicting the phenotypic impact of genetic variation, but their overall clinical value remains unclear. Here, we assess the ability of 15 different methods to predict HNSCC patient survival from TP53 mutation, using TP53 mutation and clinical data from patients enrolled in E4393 by the Eastern Cooperative Oncology Group (ECOG), which investigated whether TP53 mutations in surgical margins were predictive of disease recurrence. These methods include: server-based computational tools SIFT, PolyPhen-2, and Align-GVGD; our in-house POSE and VEST algorithms; the rules devised in Poeta et al. with and without considerations for splice-site mutations; location of mutation in the DNA-bound TP53 protein structure; and a functional assay measuring WAF1 transactivation in TP53-mutated yeast. We assessed method performance using overall survival (OS) and progression-free survival (PFS) from 420 HNSCC patients, of whom 224 had TP53 mutations. Each mutation was categorized as "disruptive" or "non-disruptive". For each method, we compared the outcome between the disruptive group vs. the non-disruptive group. The rules devised by Poeta et al. with or without our splice-site modification were observed to be superior to others. While the differences in OS (disruptive vs. non-disruptive) appear to be marginally significant (Poeta rules + splice rules, P = 0.089; Poeta rules, P = 0.053), both algorithms identified the disruptive group as having significantly worse PFS outcome (Poeta rules + splice rules, P = 0.011; Poeta rules, P = 0.027). In general, prognostic performance was low among assessed methods. Further studies are required to develop and validate methods that can predict functional and clinical significance of TP53 mutations in HNSCC patients.


Assuntos
Algoritmos , Carcinoma de Células Escamosas/genética , Biologia Computacional/métodos , Genética Médica/métodos , Neoplasias de Cabeça e Pescoço/genética , Mutação/genética , Proteína Supressora de Tumor p53/genética , Carcinoma de Células Escamosas/fisiopatologia , Progressão da Doença , Neoplasias de Cabeça e Pescoço/fisiopatologia , Humanos , Prognóstico , Análise de Sobrevida
8.
Laryngoscope ; 133(4): 834-840, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35634691

RESUMO

OBJECTIVE: To examine the relationship between surgeon volume and operative morbidity and mortality for laryngectomy. DATA SOURCES: The Nationwide Inpatient Sample was used to identify 45,156 patients who underwent laryngectomy procedures for laryngeal or hypopharyngeal cancer between 2001 and 2011. Hospital and surgeon laryngectomy volume were modeled as categorical variables. METHODS: Relationships between hospital and surgeon volume and mortality, surgical complications, and acute medical complications were examined using multivariable regression. RESULTS: Higher-volume surgeons were more likely to operate at large, teaching, nonprofit hospitals and were more likely to treat patients who were white, had private insurance, hypopharyngeal cancer, low comorbidity, admitted electively, and to perform partial laryngectomy, concurrent neck dissection, and flap reconstruction. Surgeons treating more than 5 cases per year were associated with lower odds of medical and surgical complications, with a greater reduction in the odds of complications with increasing surgical volume. Surgeons in the top volume quintile (>9 cases/year) were associated with a decreased odds of in-hospital mortality (OR = 0.09 [0.01-0.74]), postoperative surgical complications (OR = 0.58 [0.45-0.74]), and acute medical complications (OR = 0.49 [0.37-0.64]). Surgeon volume accounted for 95% of the effect of hospital volume on mortality and 16%-47% of the effect of hospital volume on postoperative morbidity. CONCLUSION: There is a strong volume-outcome relationship for laryngectomy, with reduced mortality and morbidity associated with higher surgeon and higher hospital volumes. Observed associations between hospital volume and operative morbidity and mortality are mediated by surgeon volume, suggesting that surgeon volume is an important component of the favorable outcomes of high-volume hospital care. Laryngoscope, 133:834-840, 2023.


Assuntos
Neoplasias Hipofaríngeas , Cirurgiões , Humanos , Laringectomia/efeitos adversos , Resultado do Tratamento , Hospitais com Alto Volume de Atendimentos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
9.
Ann Otol Rhinol Laryngol ; 121(9): 620-4, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23012902

RESUMO

OBJECTIVES: We describe our experience with the postoperative sequelae, complications, and recurrences associated with resection of a series of parapharyngeal space (PPS) tumors via a transcervical approach without submandibular gland excision, parotidectomy, or mandibulotomy. METHODS: We performed a retrospective review of 51 cases, 40 of which were pleomorphic adenomas and 11 of which were lipomas or schwannomas. RESULTS: Of 30 fine-needle aspirations performed, 24 indicated pleomorphic adenoma before operation. Twenty-eight of the 30 fine-needle aspirations yielded diagnoses that were consistent with the final pathologic diagnoses. The average hospital stay was 1.05 days. After operation, there were 9 cases of trismus, 4 cases of "first bite" pain, and 7 cases of transient marginal nerve weakness. There were no recurrences over an average follow-up of 115 months. CONCLUSIONS: The majority of PPS tumors are benign. It is important to use an approach that allows complete tumor excision but does not impart undue postoperative morbidity. We demonstrate that the transcervical approach without submandibular gland excision, parotidectomy, or mandibulotomy is ideal for benign PPS tumors.


Assuntos
Adenoma Pleomorfo/cirurgia , Lipoma/cirurgia , Neurilemoma/cirurgia , Neoplasias Otorrinolaringológicas/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Biópsia por Agulha Fina , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pescoço , Neoplasias Otorrinolaringológicas/patologia , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Faringe , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
10.
Tex Dent J ; 129(5): 491-507, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22779205

RESUMO

BACKGROUND: This article presents evidence-based clinical recommendations developed by a panel convened by the American Dental Association Council on Scientific Affairs. This report addresses the potential benefits and potential risks of screening for oral squamous cell carcinomas and the use of adjunctive screening aids to visualize and detect potentially malignant and malignant oral lesions. TYPES OF STUDIES REVIEWED: The panel members conducted a systematic search of MEDLINE, identifying 332 systematic reviews and 1,499 recent clinical studies. They selected 5 systematic reviews and 4 clinical studies to use as a basis for developing recommendations. RESULTS: The panel concluded that screening by means of visual and tactile examination to detect potentially malignant and malignant lesions may result in detection of oral cancers at early stages of development, but that there is insufficient evidence to determine if screening alters disease-specific mortality in asymptomatic people seeking dental care. CLINICAL IMPLICATIONS: The panel suggested that clinicians remain alert for signs of potentially malignant lesions or early-stage cancers while performing routine visual and tactile examinations in all patients, but particularly in those who use tobacco or who consume alcohol heavily. Additional research regarding oral cancer screening and the use of adjuncts is needed.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Odontologia Baseada em Evidências , Programas de Rastreamento/métodos , Neoplasias Bucais/diagnóstico , Consumo de Bebidas Alcoólicas , American Dental Association , Doenças Assintomáticas , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Corantes , Citodiagnóstico , Detecção Precoce de Câncer , Humanos , Incidência , Luz , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/mortalidade , Exame Físico , Guias de Prática Clínica como Assunto , Fatores de Risco , Fumar , Cloreto de Tolônio , Estados Unidos/epidemiologia
11.
Front Psychiatry ; 13: 857083, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873237

RESUMO

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.

12.
JAMA Otolaryngol Head Neck Surg ; 148(1): 70-79, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34792560

RESUMO

Importance: Human papillomavirus (HPV)-positive status in patients with oropharyngeal squamous cell carcinoma (OPSCC) is associated with improved survival compared with HPV-negative status. However, it remains controversial whether HPV is associated with improved survival among patients with nonoropharyngeal and cervical squamous cell tumors. Objective: To investigate differences in the immunogenomic landscapes of HPV-associated tumors across anatomical sites (the head and neck and the cervix) and their association with survival. Design, Setting, and Participants: This cohort study used genomic and transcriptomic data from the Cancer Genome Atlas (TCGA) for 79 patients with OPSCC, 435 with nonoropharyngeal head and neck squamous cell carcinoma (non-OP HNSCC), and 254 with cervical squamous cell carcinoma and/or endocervical adenocarcinoma (CESC) along with matched clinical data from TCGA. The data were analyzed from November 2020 to March 2021. Main Outcomes and Measures: Positivity for HPV was classified by RNA-sequencing reads aligned with the HPV reference genome. Gene expression profiles, immune cell phenotypes, cytolytic activity scores, and overall survival were compared by HPV tumor status across multiple anatomical sites. Results: The study comprised 768 patients, including 514 (66.9%) with HNSCC (380 male [73.9%]; mean [SD] age, 59.5 [10.8] years) and 254 (33.1%) with CESC (mean [SD] age, 48.7 [14.1] years). Human papillomavirus positivity was associated with a statistically significant improvement in overall survival for patients with OPSCC (adjusted hazard ratio [aHR], 0.06; 95% CI, 0.02-0.17; P < .001) but not for those with non-OP HNSCC (aHR, 0.64; 95% CI, 0.31-1.27; P = .20) or CESC (aHR, 0.50; 95% CI, 0.15-1.67; P = .30). The HPV-positive OPSCCs had increased tumor immune infiltration and immunomodulatory receptor expression compared with HPV-negative OPSCCs. Compared with HPV-positive non-OP HNSCCs, HPV-positive OPSCCs showed greater expression of immune-related metrics including B cells, T cells, CD8+ T cells, T-cell receptor diversity, B-cell receptor diversity, and cytolytic activity scores, independent of tumor variant burden. The immune-related metrics were similar when comparing HPV-positive non-OP HNSCCs and HPV-positive CESCs with their HPV-negative counterparts. The 2-year overall survival rate was significantly higher for patients with HPV-positive OPSCC compared with patients with HPV-negative OPSCC (92.0% [95% CI, 84.8%-99.9%] vs 45.8% [95% CI, 28.3%-74.1%]; HR, 0.10 [95% CI, 0.03-0.30]; P = .009). Conclusions and Relevance: In this cohort study, tumor site was associated with the immune landscape and survival among patients with HPV-related tumors despite presumed similar biologic characteristics. These tumor site-related findings provide insight on possible outcomes of HPV positivity for tumors in oropharyngeal and nonoropharyngeal sites and a rationale for the stratification of HPV-associated tumors by site and the subsequent development of strategies targeting immune exclusion in HPV-positive nonoropharyngeal cancer.


Assuntos
Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/imunologia , Neoplasias da Coluna Vertebral/genética , Neoplasias da Coluna Vertebral/imunologia , Adulto , Idoso , Alphapapillomavirus , Vértebras Cervicais/patologia , Estudos de Coortes , Feminino , Genômica , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias da Coluna Vertebral/virologia , Taxa de Sobrevida
13.
J Clin Oncol ; 40(2): 138-149, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-34699271

RESUMO

PURPOSE: Definitive or postoperative chemoradiation (CRT) is curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a deintensification strategy, we studied primary transoral surgery (TOS) and reduced postoperative radiation therapy (RT) in intermediate-risk HPV+ OPC. METHODS: E3311 is a phase II randomized trial of reduced- or standard-dose postoperative RT for resected stage III-IVa (American Joint Committee on Cancer-seventh edition) HPV+ OPC, determined by pathologic parameters. Primary goals were feasibility of prospective multi-institutional study of TOS for HPV+ OPC, and oncologic efficacy (2-year progression-free survival) of TOS and adjuvant therapy in intermediate-risk patients after resection. TOS plus 50 Gy was considered promising if the lower limit of the exact 90% binomial confidence intervals exceeded 85%. Quality of life and swallowing were measured by functional assessment of cancer therapy-head and neck and MD Anderson Dysphagia Index. RESULTS: Credentialed surgeons performed TOS for 495 patients. Eligible and treated patients were assigned as follows: arm A (low risk, n = 38) enrolled 11%, intermediate risk arms B (50 Gy, n = 100) or C (60 Gy, n = 108) randomly allocated 58%, and arm D (high risk, n = 113) enrolled 31%. With a median 35.2-month follow-up for 359 evaluable (eligible and treated) patients, 2-year progression-free survival Kaplan-Meier estimate is 96.9% (90% CI, 91.9 to 100) for arm A (observation), 94.9% (90% CI, 91.3 to 98.6]) for arm B (50 Gy), 96.0% (90% CI, 92.8 to 99.3) for arm C (60 Gy), and 90.7% (90% CI, 86.2 to 95.4) for arm D (66 Gy plus weekly cisplatin). Treatment arm distribution and oncologic outcome for ineligible or step 2 untreated patients (n = 136) mirrored the 359 evaluable patients. Exploratory comparison of functional assessment of cancer therapy-head and neck total scores between arms B and C is presented. CONCLUSION: Primary TOS and reduced postoperative RT result in outstanding oncologic outcome and favorable functional outcomes in intermediate-risk HPV+ OPC.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/análise , Cisplatino/uso terapêutico , Inibidor p16 de Quinase Dependente de Ciclina/análise , Neoplasias Orofaríngeas/terapia , Papillomaviridae/isolamento & purificação , Faringectomia , Radioterapia de Intensidade Modulada , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Quimiorradioterapia Adjuvante , Cisplatino/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/química , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Faringectomia/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/química , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Fatores de Tempo
14.
Head Neck ; 43(10): 2907-2912, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34050570

RESUMO

BACKGROUND: Head and neck cancers occur predominantly in developing countries where access to care is poor. Sub-Saharan Africa has <20 head and neck surgeons for >1 billion people and has only two fellowship training programs. METHODS AND RESULTS: The AfHNS Head and Neck Fellowship is being introduced to accelerate training of African surgeons to improve access to resource appropriate cancer care. By avoiding fixed time-in-training and single training sites, training can be offered at multiple centers in Africa, even with lower patient volumes. It also creates opportunities for accredited international surgical outreach programs to contribute to training. CONCLUSIONS: Having prescribed reading and appropriate Entrustable Professional Activities that are assessed through Workplace Based Assessment, and having a summative virtual oral examination ensures that fellows are fit-for-purpose to practice in an African resource-constrained setting. Other developing countries are encouraged to adopt a similar approach to expanding head and neck cancer services.


Assuntos
Neoplasias de Cabeça e Pescoço , Cirurgiões , África Subsaariana , Países em Desenvolvimento , Bolsas de Estudo , Neoplasias de Cabeça e Pescoço/terapia , Humanos
15.
Int J Cancer ; 126(12): 2991-6, 2010 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-19588496

RESUMO

Merkel Cell Virus (MCV) is a newly discovered polyomavirus, recently found in a rare skin cancer, Merkel cell carcinoma (MCC). However, MCV has also been detected in some normal tissue samples. We tested and compared the relative quantity of the MCV in a set of diverse human tissue samples with the MCC samples. The levels of MCV in MCCs were over 60 times higher than the highest values in all other tissues. Low quantities of MCV were detected in diverse tissue samples independently of malignant or benign histologic status. Higher levels of the virus were found in the upper aerodigestive tract, digestive system, and saliva compared to the lung and genitourinary system samples. These results confirm that MCV is widespread in the human body and suggest a possible fecal-oral transmission route similar to the Hepatitis A virus. Despite widespread presence of the virus, it appears that only neuroendocrine skin cells are susceptible to transformation by MCV.


Assuntos
Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/virologia , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/transmissão , Polyomavirus/isolamento & purificação , Proteínas do Capsídeo/genética , Carcinoma de Célula de Merkel/genética , DNA Viral/análise , DNA Viral/genética , Humanos , Reação em Cadeia da Polimerase , Polyomavirus/genética , Polyomavirus/patogenicidade , Infecções por Polyomavirus/virologia , Distribuição Tecidual
16.
N Engl J Med ; 356(19): 1944-56, 2007 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-17494927

RESUMO

BACKGROUND: Substantial molecular evidence suggests a role for human papillomavirus (HPV) in the pathogenesis of oropharyngeal squamous-cell carcinoma, but epidemiologic data have been inconsistent. METHODS: We performed a hospital-based, case-control study of 100 patients with newly diagnosed oropharyngeal cancer and 200 control patients without cancer to evaluate associations between HPV infection and oropharyngeal cancer. Multivariate logistic-regression models were used for case-control comparisons. RESULTS: A high lifetime number of vaginal-sex partners (26 or more) was associated with oropharyngeal cancer (odds ratio, 3.1; 95% confidence interval [CI], 1.5 to 6.5), as was a high lifetime number of oral-sex partners (6 or more) (odds ratio, 3.4; 95% CI, 1.3 to 8.8). The degree of association increased with the number of vaginal-sex and oral-sex partners (P values for trend, 0.002 and 0.009, respectively). Oropharyngeal cancer was significantly associated with oral HPV type 16 (HPV-16) infection (odds ratio, 14.6; 95% CI, 6.3 to 36.6), oral infection with any of 37 types of HPV (odds ratio, 12.3; 95% CI, 5.4 to 26.4), and seropositivity for the HPV-16 L1 capsid protein (odds ratio, 32.2; 95% CI, 14.6 to 71.3). HPV-16 DNA was detected in 72% (95% CI, 62 to 81) of 100 paraffin-embedded tumor specimens, and 64% of patients with cancer were seropositive for the HPV-16 oncoprotein E6, E7, or both. HPV-16 L1 seropositivity was highly associated with oropharyngeal cancer among subjects with a history of heavy tobacco and alcohol use (odds ratio, 19.4; 95% CI, 3.3 to 113.9) and among those without such a history (odds ratio, 33.6; 95% CI, 13.3 to 84.8). The association was similarly increased among subjects with oral HPV-16 infection, regardless of their tobacco and alcohol use. By contrast, tobacco and alcohol use increased the association with oropharyngeal cancer primarily among subjects without exposure to HPV-16. CONCLUSIONS: Oral HPV infection is strongly associated with oropharyngeal cancer among subjects with or without the established risk factors of tobacco and alcohol use.


Assuntos
Carcinoma de Células Escamosas/virologia , Papillomavirus Humano 16/isolamento & purificação , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Alphapapillomavirus/isolamento & purificação , Anticorpos Antivirais/sangue , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , DNA Viral/isolamento & purificação , Feminino , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/imunologia , Humanos , Hibridização In Situ , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Boca/virologia , Análise Multivariada , Higiene Bucal , Neoplasias Orofaríngeas/etiologia , Neoplasias Orofaríngeas/patologia , Fatores de Risco , Comportamento Sexual , Fumar/efeitos adversos , Fumar/epidemiologia
17.
N Engl J Med ; 357(25): 2552-61, 2007 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-18094376

RESUMO

BACKGROUND: The abrogation of function of the tumor-suppressor protein p53 as a result of mutation of its gene, TP53, is one of the most common genetic alterations in cancer cells. We evaluated TP53 mutations and survival in patients with squamous-cell carcinoma of the head and neck. METHODS: A total of 560 patients with squamous-cell carcinoma of the head and neck who were treated surgically with curative intent were enrolled in our prospective multicenter, 7-year study. TP53 mutations were analyzed in DNA from the tumor specimens with the use of the Affymetrix p53 chip and the Surveyor DNA endonuclease and denaturing high-performance liquid chromatography. Mutations were classified into two groups, disruptive and nondisruptive, according to the degree of disturbance of protein structure predicted from the crystal structure of the p53-DNA complexes. TP53 mutational status was compared with clinical outcome. RESULTS: TP53 mutations were found in tumors from 224 of 420 patients (53.3%). As compared with wild-type TP53, the presence of any TP53 mutation was associated with decreased overall survival (hazard ratio for death, 1.4; 95% confidence interval [CI], 1.1 to 1.8; P=0.009), with an even stronger association with disruptive mutations (hazard ratio, 1.7; 95% CI, 1.3 to 2.4; P<0.001) and no significant association with nondisruptive mutations (hazard ratio, 1.2; 95% CI, 0.9 to 1.7; P=0.16). In multivariate analyses a disruptive TP53 alteration, as compared with the absence of a TP53 mutation, had an independent, significant association with decreased survival (hazard ratio, 1.7; 95% CI, 1.2 to 2.4; P=0.003). CONCLUSIONS: Disruptive TP53 mutations in tumor DNA are associated with reduced survival after surgical treatment of squamous-cell carcinoma of the head and neck.


Assuntos
Carcinoma de Células Escamosas/genética , DNA de Neoplasias , Genes p53 , Neoplasias de Cabeça e Pescoço/genética , Mutação , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Análise Mutacional de DNA , DNA de Neoplasias/análise , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos
18.
Oncogene ; 39(40): 6327-6339, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32848210

RESUMO

The dominant paradigm for HPV carcinogenesis includes integration into the host genome followed by expression of E6 and E7 (E6/E7). We explored an alternative carcinogenic pathway characterized by episomal E2, E4, and E5 (E2/E4/E5) expression. Half of HPV positive cervical and pharyngeal cancers comprised a subtype with increase in expression of E2/E4/E5, as well as association with lack of integration into the host genome. Models of the E2/E4/E5 carcinogenesis show p53 dependent enhanced proliferation in vitro, as well as increased susceptibility to induction of cancer in vivo. Whole genomic expression analysis of the E2/E4/E5 pharyngeal cancer subtype is defined by activation of the fibroblast growth factor receptor (FGFR) pathway and this subtype is susceptible to combination FGFR and mTOR inhibition, with implications for targeted therapy.


Assuntos
Carcinogênese/genética , Proteínas Oncogênicas Virais/genética , Infecções por Papillomavirus/genética , Neoplasias Faríngeas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Neoplasias do Colo do Útero/genética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinogênese/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/genética , Conjuntos de Dados como Assunto , Modelos Animais de Doenças , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/patogenicidade , Humanos , Camundongos , Camundongos Transgênicos , Infecções por Papillomavirus/tratamento farmacológico , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/virologia , Neoplasias Faríngeas/tratamento farmacológico , Neoplasias Faríngeas/mortalidade , Neoplasias Faríngeas/virologia , Cultura Primária de Células , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/virologia
20.
Oral Oncol ; 110: 104797, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32679405

RESUMO

PURPOSE: Understanding the role of transoral surgery in oropharyngeal cancer (OPC) requires prospective, randomized multi-institutional data. Meticulous evaluation of surgeon expertise and surgical quality assurance (QA) will be critical to the validity of such trials. We describe a novel surgeon credentialing and QA process developed to support the ECOG-ACRIN Cancer Research Group E3311 (E3311) and report outcomes related to QA. PATIENTS AND METHODS: E3311 was a phase II randomized clinical trial of transoral surgery followed by low- or standard-dose, risk-adjusted post-operative therapy with stage III-IVa (AJCC 7th edition) HPV-associated OPC. In order to be credentialed to accrue to this trial, surgeons were required to demonstrate active hospital credentials and technique-specific surgical expertise with ≥20 cases of transoral resection for OPC. In addition, 10 paired operative and surgical pathology reports from the preceding 24 months were reviewed by an expert panel. Ongoing QA required <10% rate of positive margins, low oropharyngeal bleeding rates, and accrual of at least one patient per 12 months. Otherwise surgeons were placed on hold and not permitted to accrue until re-credentialed using a new series of transoral resections. RESULTS: 120 surgeons trained in transoral minimally invasive surgery applied for credentialing for E3311 and after peer-review, 87 (73%) were approved from 59 centers. During QA on E3311, positive final pathologic margins were reported in 19 (3.8%) patients. Grade III/IV and grade V oropharyngeal bleeding was reported in 29 (5.9%) and 1 (0.2%) of patients. CONCLUSIONS: We provide proof of concept that a comprehensive credentialing process can support multicenter transoral head and neck surgical oncology trials, with low incidence of positive margins and *grade III/V oropharyngeal bleeding.


Assuntos
Neoplasias Orofaríngeas/cirurgia , Garantia da Qualidade dos Cuidados de Saúde/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Cirurgiões
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