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1.
Klin Onkol ; 38(3): 202-208, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38960676

RESUMO

BACKGROUND: Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. MATERIAL AND METHODS: Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. RESULTS: A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). CONCLUSION: SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.


Assuntos
Quimiorradioterapia , Neoplasias Orofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/tratamento farmacológico , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento
2.
BMC Oral Health ; 24(1): 729, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918827

RESUMO

BACKGROUND: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before. METHODS: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression. RESULTS: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043). CONCLUSIONS: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Proteínas com Domínio LIM , Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Proteínas com Domínio LIM/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Idoso , Fatores de Transcrição/metabolismo , Glicoproteínas de Membrana/metabolismo , Adulto , Antígeno Ki-67/metabolismo , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/análise , Proteína Supressora de Tumor p53/metabolismo , Infecções por Papillomavirus/complicações , Imuno-Histoquímica , Idoso de 80 Anos ou mais , Taxa de Sobrevida
3.
Oral Oncol ; 154: 106808, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823172

RESUMO

BACKGROUND: An estimated 20% of patients with oral and oropharyngeal squamous cell carcinoma (OOSCC) have micrometastases (Mi) or isolated tumor cells (ITC) in the cervical lymph nodes that evade detection by standard histological evaluation of lymph node sections. Lymph node Mi and ITC could be one reason for regional recurrence after neck dissection. The aim of this study was to review the existing data regarding the impact of Mi on the survival of patients with OOSCC. METHODS: PubMed and the Cochrane Library were searched for articles reporting the impact of Mi and ITC on patient survival. Two authors independently assessed the methodological quality of retrieved studies using the Downs and Black index. Data were also extracted on study type, number of included patients, mode of histological analysis, statistical analysis, and prognostic impact. RESULTS: Sixteen articles with a total of 2064 patients were included in the review. Among the 16 included studies, eight revealed a statistically significant impact of Mi on at least one endpoint in the Kaplan-Meier and/or multivariate analysis. Three studies regarded Mi as Ma, while five studies found no impact of Mi on survival. Only one study demonstrated an impact of ITC on patient's prognosis in the univariate but not in the multivariate analysis. CONCLUSION: The majority of cases included in the review were patients with oral cancer. The findings provide low-certainty evidence that Mi negatively impacts survival. Data on ITC were scarcer, so no conclusions can be drawn about their effect on survival. The lower threshold to discriminate between Mi and ITC should be defined for OOSCC since the existing thresholds are based on data from different tumors. The histological, immunohistological, and anatomical characteristics of Mi and ITC in OOSCC as well as the effect of radiotherapy on Mi should be further investigated separately for oral and oropharyngeal carcinomas.


Assuntos
Metástase Linfática , Neoplasias Bucais , Micrometástase de Neoplasia , Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Bucais/patologia , Neoplasias Bucais/mortalidade , Prognóstico , Micrometástase de Neoplasia/patologia , Linfonodos/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade
4.
Am J Otolaryngol ; 45(4): 104356, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38703611

RESUMO

PURPOSE: This study compared treatment and outcomes for patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) based on their travel distance to treatment facility. MATERIALS AND METHODS: Patients with cT1-4, N0-3, M0 HPV-positive OPSCC in the National Cancer Database from 2010 to 2019 were identified and split into four quartiles based on distance to facility, with quartile 4 representing patients with furthest travel distances. Multivariable-adjusted logistic regression and Cox proportional hazards modeling were used to analyze the primary outcome of treatment received, and secondary outcomes of clinical stage, overall survival, surgical approach (i.e., TORS versus other), and 30-day surgical readmissions. RESULTS: 17,207 patients with HPV-positive OPSCC were evenly distributed into four quartiles. Compared to patients in quartile 1, patients in quartile 4 were 40 % less likely to receive radiation versus surgery (OR = 0.60; 95 % CI = 0.54-0.66). Among the patients who received surgery, quartile 4 had a higher odds of receiving TORS treatment compared to quartile 1 (4v1: OR = 2.38; 95 % CI = 2.05-2.77), quartile 2 (4v2: OR = 2.31, 95 % CI = 2.00-2.66), and quartile 3 (4v3: OR = 1.75; 95 % CI = 1.54-1.99). Quartile 4 had a decreased odds of mortality compared to Quartile 1 (4v1: OR = 0.87; 95 % CI = 0.79-0.97). There were no differences among the quartiles in presenting stage and 30-day readmissions. CONCLUSIONS: This study found that patients with furthest travel distance to facility were more often treated surgically over non-surgical management, with TORS over open surgery, and had better overall survival. These findings highlight potential disparities in access to care for patients with HPV-positive OPSCC.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Masculino , Feminino , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Pessoa de Meia-Idade , Idoso , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/virologia , Resultado do Tratamento , Acessibilidade aos Serviços de Saúde , Estadiamento de Neoplasias , Taxa de Sobrevida , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Viagem , Fatores de Tempo
5.
PeerJ ; 12: e17391, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784388

RESUMO

Objective: To evaluate the efficacy and safety of cetuximab instead of cisplatin in combination with downstaging radiotherapy for papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC). Design: Meta-analysis and systematic evaluation. Data sources: The PubMed, Embase, Web of Science, and Cochrane library databases were searched up to June 8, 2023, as well as Clinicaltrials.gov Clinical Trials Registry, China Knowledge Network, Wanfang Data Knowledge Service Platform, and Wiprojournal.com. Eligibility criteria for selecting studies: Randomized controlled trials reporting results of standard regimens of cetuximab + radiotherapy vs cisplatin + radiotherapy in treating HPV+ OPSCC were included. The primary outcomes of interest were overall survival (OS), progression-free survival (PFS), local regional failure rate (LRF), distant metastasis rate (DM), and adverse events (AE). Data extraction and synthesis: Two reviewers independently extracted data and assessed the risk of bias of the included studies. The HR and its 95% CI were used as the effect analysis statistic for survival analysis, while the OR and its 95% CI were used as the effect analysis statistic for dichotomous variables. These statistics were extracted by the reviewers and aggregated using a fixed-effects model to synthesise the data. Results: A total of 874 relevant papers were obtained from the initial search, and five papers that met the inclusion criteria were included; a total of 1,617 patients with HPV+ OPSCC were enrolled in these studies. Meta-analysis showed that OS and PFS were significantly shorter in the cetuximab + radiotherapy group of patients with HPV+ OPSCC compared with those in the conventional cisplatin + radiotherapy group (HR = 2.10, 95% CI [1.39-3.15], P = 0.0004; HR = 1.79, 95% CI [1.40-2.29], P < 0.0001); LRF and DM were significantly increased (HR = 2.22, 95% CI [1.58-3.11], P < 0.0001; HR = 1.66, 95% CI [1.07-2.58], P = 0.02), but there was no significant difference in overall grade 3 to 4, acute and late AE overall (OR = 0.86, 95% CI [0.65-1.13], P = 0.28). Conclusions: Cisplatin + radiotherapy remains the standard treatment for HPV+ OPSCC. According to the 7th edition AJCC/UICC criteria, low-risk HPV+ OPSCC patients with a smoking history of ≤ 10 packs/year and non-pharyngeal tumors not involved in lymphatic metastasis had similar survival outcomes with cetuximab/cisplatin + radiotherapy. However, further clinical trials are necessary to determine whether cetuximab + radiotherapy can replace cisplatin + radiotherapy for degraded treatment in individuals who meet the aforementioned characteristics, particularly those with platinum drug allergies. Prospero registration number: CRD42023445619.


Assuntos
Cetuximab , Quimiorradioterapia , Cisplatino , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Cetuximab/uso terapêutico , Cetuximab/efeitos adversos , Cetuximab/administração & dosagem , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/tratamento farmacológico , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/mortalidade , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , 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/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Estadiamento de Neoplasias , Papillomaviridae , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Intervalo Livre de Progressão , Papillomavirus Humano
6.
Oral Oncol ; 152: 106783, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38569317

RESUMO

INTRODUCTION: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in recent decades, driven by infection with human papillomavirus (HPV). Transoral robotic surgery (TORS) and neck dissection (ND) has been employed as an alternative to radiotherapy/chemoradiotherapy. The current literature is lacking studies providing an exhaustive overview of recurrence characteristics and long-term outcomes in TORS-treated OPSCC-patients. METHODS: All patients treated for OPSCC with primary TORS + ND in Eastern Denmark between 2013 and 2020 were included in the study. The aim was to explore overall survival (OS), recurrence-free survival (RFS), recurrence patterns, and ultimate failure rate (UFR). OS and RFS were examined using the Kaplan-Meier method. Cox proportional regression analyses were employed to examine effect of different variables on risk of death and recurrence. RESULTS: The study included 153 patients of which 88.9 % (n = 136) were treated with TORS alone while 11.1 % (n = 17) received adjuvant therapy. The 1-, 3-, and 5-year OS were 97.4 %, 94.1 %, and 87.6 % while 1-, 3-, and 5-year RFS were 96.6 %, 87.8 %, and 84.9 %. The UFR was 6.5 % in the cohort. Patients with HPV+/p16 + OPSCC had a significantly better 5-year OS of 92.3 % than patients with discordant or double-negative HPV/p16 status (OS = 73.3 %). No differences in outcomes between patients treated with or without adjuvant therapy were found in regression analysis. CONCLUSION: Excellent survival and disease control was obtained with TORS + ND in this cohort, despite lesser application of adjuvant therapy than other TORS-centers, implying that TORS without adjuvant therapy can be successfully applied in treatment of early-stage OPSCC.


Assuntos
Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Feminino , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Pessoa de Meia-Idade , Idoso , Resultado do Tratamento , Adulto , Recidiva Local de Neoplasia , Idoso de 80 Anos ou mais , Estadiamento de Neoplasias , Esvaziamento Cervical/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Estudos Retrospectivos
7.
J Chin Med Assoc ; 87(5): 516-524, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38501795

RESUMO

BACKGROUND: The presence of p16 and neck disease is important predictors of prognosis for oropharyngeal squamous cell carcinoma (OPSCC). Patients who are p16-negative and have clinically node-positive (cN+) disease generally have worse oncologic outcomes. This study aimed to investigate whether upfront neck dissection (UFND) could provide potential benefits for patients with cN+ p16-negative OPSCC. METHODS: Through this retrospective study, 76 patients with cN+ p16-negative OPSCC were analyzed, those who received either definite concurrent chemoradiotherapy (CCRT group) or UFND followed by chemoradiotherapy (UFND group). The primary endpoints were regional recurrence-free survival (RRFS), disease-specific survival (DSS), and overall survival (OS). Factors associated with survival were evaluated by univariate and multivariate analysis. Survival between the two groups was compared by propensity score-matched analysis. RESULTS: Matched 23 patients in each group through propensity analysis, the UFND group showed a significantly better 5-year RRFS (94.1% vs 61.0%, p = 0.011) compared to the CCRT group. Univariate analysis revealed that UFND was the sole factor associated with regional control (hazard ratio [HR] = 0.110; 95% CI, 0.014-0.879; p = 0.037). Furthermore, the study found that the CCRT group was associated with a higher dose of radiotherapy and exhibited a significantly higher risk of mortality due to pneumonia. CONCLUSION: The study indicated that UFND followed by CCRT may be a potential treatment option for patients with cN+ p16-negative OPSCC, as it can reduce the risk of regional recurrence. Additionally, the study highlights that definite CCRT is connected to a larger dose of radiotherapy and a higher risk of fatal pneumonia. These findings could be beneficial in informing clinical decision-making and improving treatment outcomes for patients with OPSCC.


Assuntos
Quimiorradioterapia , Inibidor p16 de Quinase Dependente de Ciclina , Esvaziamento Cervical , Neoplasias Orofaríngeas , Feminino , Humanos , Masculino , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidade , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/mortalidade , Pontuação de Propensão , Estudos Retrospectivos
8.
Clin Cancer Res ; 30(11): 2393-2401, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38517480

RESUMO

PURPOSE: Locoregionally advanced HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has excellent cure rates, although current treatment regimens are accompanied by acute and long-term toxicities. We designed a phase II deescalation trial for patients with HPV+ OPSCC to evaluate the feasibility of an upfront neck dissection to individualize definitive treatment selection to improve the quality of life without compromising survival. PATIENTS AND METHODS: Patients with T1-3, N0-2 HPV+ OPSCC underwent an upfront neck dissection with primary tumor biopsy. Arm A included patients with a single lymph node less than six centimeters, with no extracapsular spread (ECS) and no primary site adverse features underwent transoral surgery. Arm B included patients who had two or more positive lymph nodes with no ECS, or those with primary site adverse features were treated with radiation alone. Arm C included patients who had ECS in any lymph node and were treated with chemoradiation. The primary endpoint was quality of life at 1 year compared with a matched historical control. RESULTS: Thirty-four patients were enrolled and underwent selective neck dissection. On the basis of pathologic characteristics, 14 patients were assigned to arm A, 10 patients to arm B, and 9 to arm C. A significant improvement was observed in Head and Neck Quality of Life (HNQOL) compared with historical controls (-2.6 vs. -11.9, P = 0.034). With a median follow-up of 37 months, the 3-year overall survival was 100% and estimated 3-year estimated progression-free survival was 96% [95% confidence interval (CI), 76%-99%]. CONCLUSIONS: A neck dissection-driven treatment paradigm warrants further research as a deintensification strategy.


Assuntos
Esvaziamento Cervical , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Qualidade de Vida , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/cirurgia , Idoso , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Adulto , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estadiamento de Neoplasias , Quimiorradioterapia/métodos , Resultado do Tratamento , Papillomaviridae/isolamento & purificação
9.
Eur Arch Otorhinolaryngol ; 281(6): 3157-3166, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38503971

RESUMO

PURPOSE: The optimal treatment strategy for oropharyngeal cancer (OPC) is undetermined. We aim to compare the survival outcomes of OPC patients treated with upfront surgery versus definitive radiotherapy (RT). METHODS: A total of 8057 cases were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer-specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine-Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity-score-matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)-negative and HPV-positive cohorts. RESULTS: In the HPV-negative cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted subdistribution hazard ratio [SHR], 1.31; 95% confidence interval [CI], 1.05-1.64; P = 0.017) and noncancer mortality (adjusted SHR, 1.59; 95% CI 1.13-2.25; P = 0.008). In the HPV-positive cohort, definitive RT was independently associated with increased risk of cancer-specific mortality (adjusted SHR, 1.51; 95% CI 1.23-1.85; P < 0.001) and noncancer mortality (adjusted SHR, 1.53; 95% CI 1.11-2.12; P = 0.009). CONCLUSION: Upfront surgery is a superior treatment modality compared with definitive RT in terms of lowering cancer-specific and noncancer mortality in OPC patients, regardless of HPV status. Further prospective clinical trials are needed to confirm our findings.


Assuntos
Neoplasias Orofaríngeas , Programa de SEER , Humanos , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Medição de Risco , Infecções por Papillomavirus/radioterapia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Pontuação de Propensão , Estudos Retrospectivos , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia
10.
Eur Arch Otorhinolaryngol ; 281(6): 3167-3177, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38546850

RESUMO

PURPOSE: Salvage surgery is still the best therapeutic option for resectable recurrent oropharyngeal squamous cell carcinoma (rOPSCC). Transoral robotic surgery may potentially reduce the morbidity of standard open approaches. The aim of the study is to present oncological and functional outcomes of a monocentric experience in salvage transoral robotic surgery. METHODS: We performed a single-center retrospective analysis of patients submitted to transoral robotic salvage surgery with or without neck dissection for cT1-3 rOPSCC. We investigated complication rate, survival outcomes (Overall Survival, Disease Specific Survival, Loco-Regional Recurrence Free Survival) and functional outcomes (tracheal tube and/or gastrostomy dependence). RESULTS: Sixty-one patients were included in the analysis. No major complications or perioperative deaths were recorded. The estimated 2-year OS was 76.7%, DSS 81.8% and LRRFS 50.5%. In multivariable analysis rpT, PNI (perineural infiltration) and HPV-positivity were significantly associated with LRRFS (Hazard Ratios: T3 vs T1 6.43, PNI yes vs no 4.19, HPV+ yes vs no 2.63). At last follow up, 97% of patients were tracheal tube-free, while 93% were gastrostomy-free. CONCLUSION: Transoral robotic salvage surgery is a successful treatment in selected patients affected by rOPSCC because it grants good oncologic and functional outcomes.


Assuntos
Carcinoma de Células Escamosas , Recidiva Local de Neoplasia , Neoplasias Orofaríngeas , Procedimentos Cirúrgicos Robóticos , Terapia de Salvação , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Estudos Retrospectivos , Masculino , Terapia de Salvação/métodos , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Idoso , Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Esvaziamento Cervical/métodos , Adulto , Resultado do Tratamento , Cirurgia Endoscópica por Orifício Natural/métodos , Idoso de 80 Anos ou mais
11.
Head Neck ; 46(6): 1294-1303, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38497289

RESUMO

BACKGROUND: The prevalence of HPV-negative oropharyngeal cancer (OPC) is higher in Asian countries. Patients with HPV-negative OPC suffer poor outcomes. Multi-omics analysis could provide researchers and clinicians with more treatment targets for this high-risk group. We aimed to explore the prognostic significance of EGFR overexpression and macrophage infiltration in OPC, especially HPV-negative OPC in this study. METHODS: EGFR alternation was evaluated with TCGA, PanCancer Atlas through cBioProtal. EGFR mRNA expression in HPV-negative head and neck squamous cell carcinoma was analyzed using the Tumor Immune Estimation Resource (TIMER 2.0). We also examined EGFR/STAT6/MRC1 expression in paraffin-embedded tissues from a p16-negative OPC cohort. The correlation between EGFR expression and macrophage activation was explored using Person's correlation coefficient. The impact of biomarkers or macrophage infiltration on 5-year overall survival and recurrence-free survival were analyzed using Kaplan-Meier survival curves. RESULTS: EGFR alteration rate was 15%, 13%, and 0% for HPV-negative HNSCC (excluding OPC), HPV-negative OPC, and HPV-positive OPC. High EGFR expression was associated with increased tumor infiltration of immune cells, such as macrophages. We observed positive correlations between EGFR, STAT6, and MRC1 expression in p16-negative OPC. Higher MRC1 expression was associated with poorer survival rates. CONCLUSIONS: There is strong correlation between EGFR overexpression and M2 polarization in patients with p16-negative OPC. Immunotherapy with or without EGFR inhibitor could be considered in these high-risk patients.


Assuntos
Receptores ErbB , Neoplasias Orofaríngeas , Fator de Transcrição STAT6 , Humanos , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/terapia , Fator de Transcrição STAT6/metabolismo , Fator de Transcrição STAT6/genética , Receptores ErbB/metabolismo , Receptores ErbB/genética , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Macrófagos/metabolismo , Transdução de Sinais , Idoso , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Biomarcadores Tumorais/metabolismo
12.
Med Mol Morphol ; 57(2): 136-146, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38459388

RESUMO

The purpose of this study was to assess the clinicopathological features of oropharyngeal cancer patients in Jordan based on their HPV status. Sixty-nine biopsies from two hospitals were included. Tissue microarrays were prepared from formalin-fixed paraffin-embedded (FFPE) specimens and stained with antibodies for CDKN2A/P16, EGFR, PI3K, PTEN, AKT, pS473AKT, PS2mTOR, and TIMAP. The cohort was divided according to P16 expression. Chi-square test and survival analyses were employed to evaluate the variations among the study variables and determine the prognostic factors, respectively. P16 expression was found in 55.1% of patients; however, there was no significant association between P16 expression and the patients' clinicopathological features. The Kaplan-Meier test revealed that smoking in P16-positive group and younger age (< 58 years) negatively impacted disease-free survival (DFS) (P = 0.04 and P = 0.003, respectively). Multivariate Cox regression test indicated that smoking, age, PI3K, and AKT were negative predictors of DFS (P = 0.021, P = 0.002, P = 0.021, and P = 0.009, respectively), while TIMAP was a positive predictor (P = 0.045). Elevated P16 expression is found in more than half of the patients' specimens. DFS is negatively affected by younger age and the combined effect of smoking and P16 overexpression. TIMAP is overexpressed in P16-positive oropharyngeal cancer, and it is a favorable predictor of DFS.


Assuntos
Biomarcadores Tumorais , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/diagnóstico , Feminino , Pessoa de Meia-Idade , Masculino , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Estudos Retrospectivos , Jordânia/epidemiologia , Idoso , Adulto , Prognóstico , Intervalo Livre de Doença , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estimativa de Kaplan-Meier , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações
13.
Otolaryngol Head Neck Surg ; 171(1): 124-137, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38532532

RESUMO

OBJECTIVE: Evaluate the effect of treatment delay on survival in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing primary surgical resection. STUDY DESIGN: Retrospective cohort study using the 2010-2017 National Cancer Database. SETTING: Multicenter database study. METHODS: Patients >18 years old with OPSCC and known HPV status, treated surgically with or without postoperative radiation/chemotherapy were included. Two cohorts based on HPV status were grouped by time to treatment initiation (TD-TI, ≤30, 31-60, ≥61 days) and surgery to radiotherapy (TS-RT, ≤42, 43-66, ≥67 days). Univariate, Kaplan-Meier, and multivariate analyses assessed correlations between demographic and clinical factors with overall survival in treatment delay groups. RESULTS: Included were 1643 HPV-positive OPSCC patients and 391 HPV-negative OPSCC patients. No associations between survival and gender, age, race, insurance, or radiotherapy length were observed. Regardless of HPV status, larger tumor size (>2 cm) and lymphovascular invasion predicted worse survival. HPV negative patients with >4 lymph nodes involved had 2.5× greater mortality risk (P = .039). Robotic surgery was associated with improved survival only in HPV positive patients (hazard ratio [HR]: 0.41, P < .001). In HPV positive patients, higher TD-TI related to lower mean survival, although this was not significant on multivariate analysis. HPV negative patients with >42 days of TS-RT had decreased survival (43-66 days, HR 1.63, P = .049; ≥67 days, HR 2.10, P = .032). CONCLUSION: Longer TS-RT was associated with lower overall survival in HPV negative patients. Treatment delay was not associated with survival in HPV positive OPSCC according to multivariate analysis. These findings enhance knowledge about treatment delay effects in OPSCC, aiding providers in decisions and patient communication.


Assuntos
Bases de Dados Factuais , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Tempo para o Tratamento , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Idoso , Estados Unidos/epidemiologia , Taxa de Sobrevida , Atraso no Tratamento
14.
J Natl Cancer Inst ; 116(7): 1051-1062, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38167712

RESUMO

BACKGROUND: Studies have shown lower overall survival for patients with head and neck cancer treated at low-volume or community cancer centers. As the incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma steadily rises in the United States, we hypothesized that a greater proportion of patients with HPV-related oropharyngeal squamous cell carcinoma is being treated at community cancer centers, with a shift toward primary nonsurgical treatment. METHODS: This cohort study included patients from the US National Cancer Database who received a diagnosis of HPV-related oropharyngeal squamous cell carcinoma from 2010 to 2019 and underwent treatment at a community cancer center or academic cancer center. The proportion of patients with HPV-related oropharyngeal squamous cell carcinoma treated at community cancer centers and receiving primary nonsurgical treatment was analyzed over time. Four-year overall survival was compared between community cancer centers and academic cancer centers. RESULTS: The majority (67.4%) of 20 298 patients were treated at an academic cancer center, yet the proportion of patients treated at community cancer centers increased by 10% from 2010 to 2019 (P < .01 for trend). The proportion of patients undergoing primary nonsurgical treatment increased from 62.1% to 73.7% from 2010 to 2019 (P < .01 for trend), and patients were statistically significantly more likely to undergo nonsurgical treatment at community cancer centers than at academic cancer centers (adjusted odds ratio = 1.20, 95% confidence interval = 1.18 to 1.22). Treatment at community cancer centers was associated with worse survival overall (adjusted hazard ratio = 1.19, 95% confidence interval = 1.09 to 1.31), specifically for patients receiving primary nonsurgical treatment (adjusted hazard ratio = 1.22, 95% confidence interval = 1.11 to 1.34). CONCLUSIONS: Treatment of HPV-related oropharyngeal squamous cell carcinoma has recently shifted to community cancer centers, with an increase in the proportion of nonsurgical treatment and worse overall survival at these centers compared with academic cancer centers. Concentration of care for HPV-related oropharyngeal squamous cell carcinoma at academic cancer centers and dedicated head and neck cancer centers may increase access to all available treatment modalities and improve survival.


Assuntos
Institutos de Câncer , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Infecções por Papillomavirus/virologia , Idoso , Institutos de Câncer/estatística & dados numéricos , Estados Unidos/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Taxa de Sobrevida , Papillomavirus Humano
15.
Head Neck ; 46(8): 1881-1892, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38269627

RESUMO

BACKGROUND: Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite. METHODS: Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival. RESULTS: BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors. CONCLUSIONS: This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted.


Assuntos
Índice de Massa Corporal , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/patologia , Estudos Prospectivos , Idoso , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Prognóstico , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/mortalidade , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/virologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Modelos de Riscos Proporcionais , Intervalo Livre de Doença , Adulto , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/terapia , Neoplasias Orofaríngeas/patologia , Taxa de Sobrevida , Análise de Sobrevida
16.
Laryngoscope ; 134(7): 3158-3164, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38294283

RESUMO

OBJECTIVE: While tobacco use is understood to negatively impact HPV+ oropharyngeal squamous cell carcinoma (OPSCC) outcomes, debate remains as to how this impact differs between cohorts. Multiple smoking metrics have been identified as having the greatest prognostic significance, and some recent works have found smoking to have no significant impact. Herein, we show through an analysis of four common smoking metrics that while smoking impacts overall survival (OS), it has a limited impact on recurrence-free survival (RFS) in our cohort. METHODS: We conducted a retrospective review of patients treated for HPV+ OPSCC in our health system from 2012 to 2019. Patients with metastatic disease or concurrent second primaries were excluded. Four metrics of tobacco use were assessed: current/former/never smokers, ever/never smokers, and smokers with >10 or >20 pack-year (PY) smoking histories. Our main outcomes were 3-year RFS and OS. RESULTS: Three hundred and sixty-seven patients met inclusion criteria. 37.3% of patients (137/367) were never-smokers; 13.8% of patients (51/367) were currently smoking at diagnosis and 48.8% of patients (179/367) were former smokers. No tobacco-use metric significantly impacted 3-year RFS. On univariate analysis, all smoking metrics yielded inferior OS. On multivariate analysis, current and ever smoking status significantly impacted 3-year OS. CONCLUSION: The impact of tobacco use on HPV+ OPSCC outcomes is not universal, but may instead be modulated by other cohort-specific factors. The impact of smoking may decrease as rates of tobacco use decline. LEVEL OF EVIDENCE: 3 (Cohort and case-control studies) Laryngoscope, 134:3158-3164, 2024.


Assuntos
Neoplasias Orofaríngeas , Infecções por Papillomavirus , Fumar , Humanos , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/mortalidade , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/mortalidade , Fumar/efeitos adversos , Fumar/epidemiologia , Idoso , Prognóstico , Taxa de Sobrevida , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Intervalo Livre de Doença
18.
BMC Cancer ; 22(1): 296, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313837

RESUMO

BACKGROUND: The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan. METHODS: Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records. RESULTS: In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999-2002), 30% (2003-2006), 30% (2007-2010), 29% (2011-2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999-2002), 1.06 (2003-2006), 1.52 (2007-2010) to 1.74 (2011-2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35-0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01). CONCLUSION: The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.


Assuntos
Areca/efeitos adversos , Neoplasias Orofaríngeas/epidemiologia , Neoplasias Orofaríngeas/virologia , Infecções por Papillomavirus/complicações , Feminino , Genótipo , Comportamentos de Risco à Saúde , Papillomavirus Humano 16/genética , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Mastigação , Neoplasias Orofaríngeas/mortalidade , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Taiwan/epidemiologia
19.
Clin Epigenetics ; 14(1): 1, 2022 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980250

RESUMO

BACKGROUND: Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed "epigenetic age acceleration", has been shown to predict age-related disease and mortality. We aimed to assess the prognostic value of epigenetic age acceleration and a DNA methylation-based mortality risk score with all-cause mortality in a prospective clinical cohort of individuals with head and neck cancer: Head and Neck 5000. We investigated two markers of intrinsic epigenetic age acceleration (IEAAHorvath and IEAAHannum), one marker of extrinsic epigenetic age acceleration (EEAA), one optimised to predict physiological dysregulation (AgeAccelPheno), one optimised to predict lifespan (AgeAccelGrim) and a DNA methylation-based predictor of mortality (ZhangScore). Cox regression models were first used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of epigenetic age acceleration with all-cause mortality in people with oropharyngeal cancer (n = 408; 105 deaths). The added prognostic value of epigenetic markers compared to a clinical model including age, sex, TNM stage and HPV status was then evaluated. RESULTS: IEAAHannum and AgeAccelGrim were associated with mortality risk after adjustment for clinical and lifestyle factors (HRs per standard deviation [SD] increase in age acceleration = 1.30 [95% CI 1.07, 1.57; p = 0.007] and 1.40 [95% CI 1.06, 1.83; p = 0.016], respectively). There was weak evidence that the addition of AgeAccelGrim to the clinical model improved 3-year mortality prediction (area under the receiver operating characteristic curve: 0.80 vs. 0.77; p value for difference = 0.069). CONCLUSION: In the setting of a large, clinical cohort of individuals with head and neck cancer, our study demonstrates the potential of epigenetic markers of ageing to enhance survival prediction in people with oropharyngeal cancer, beyond established prognostic factors. Our findings have potential uses in both clinical and non-clinical contexts: to aid treatment planning and improve patient stratification.


Assuntos
Envelhecimento/genética , Biomarcadores , Metilação de DNA/genética , Epigenômica , Neoplasias Orofaríngeas/genética , Neoplasias Orofaríngeas/mortalidade , Taxa de Sobrevida , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Reino Unido
20.
Int J Cancer ; 150(3): 521-531, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34655477

RESUMO

Increasing evidence has elucidated the clinicopathological significance of tumor microenvironment (TME) cells. However, TME differences associated with human papillomavirus (HPV) infection in oropharyngeal squamous cell carcinoma (OPSCC) have not been well characterized. In our study, we comprehensively determined the TME infiltration patterns in 315 OPSCC patients, and systematically correlated the TME phenotypes with genomic characteristics and clinical features of OPSCCs. In this way, we observed the enrichment of high endothelial cells and adaptive immune cells in HPV-positive (HPV+) OPSCCs, in contrast to the enrichment of fibroblasts and capillary endothelial cells in HPV- negative (HPV-) OPSCCs. By focusing on immune checkpoint genes, we constructed a coexpression network using genes that were differentially expressed between HPV+ and HPV- OPSCCs. Functional analysis of the network indicated that HPV+ OPSCCs had elevated immune activities by promoting adaptive immune response and suppressing activities related to extracellular matrix organization. Subsequently, clinical analysis showed that identified TME-relevant genes were closely associated with the prognosis and therapy response in OPSCC. Importantly, results from the TME analysis were further validated using an independent OPSCC cohort.


Assuntos
Neoplasias Orofaríngeas/virologia , Papillomaviridae/isolamento & purificação , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Microambiente Tumoral/fisiologia , Comunicação Celular , Feminino , Humanos , Proteínas de Checkpoint Imunológico/genética , Masculino , Pessoa de Meia-Idade , Neoplasias Orofaríngeas/mortalidade , Neoplasias Orofaríngeas/patologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
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