RESUMO
INTRODUCTION: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15-20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. METHODS: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. RESULTS: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14-12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. CONCLUSIONS: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC.
Assuntos
Neoplasias de Cabeça e Pescoço , Linfócitos , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Metástase Linfática/patologia , Estudos Retrospectivos , Linfócitos/patologia , Prognóstico , Linfonodos/patologia , Neoplasias de Cabeça e Pescoço/patologiaRESUMO
BACKGROUND: Inflammatory blood markers have been associated with oncological outcomes in several cancers, but evidence for head and neck squamous cell carcinoma (HNSCC) is scanty. Therefore, this study aims at investigating the association between five different inflammatory blood markers and several oncological outcomes. METHODS: This multi-centre retrospective analysis included 925 consecutive patients with primary HPV-negative HNSCC (median age: 68 years) diagnosed between April 2004 and June 2018, whose pre-treatment blood parameters were available. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated; their associations with local, regional, and distant failure, disease-free survival (DFS), and overall survival (OS) was calculated. RESULTS: The median follow-up was 53 months. All five indexes were significantly associated with OS; the highest accuracy in predicting patients' survival was found for SIM (10-year OS = 53.2% for SIM < 1.40 and 40.9% for SIM ≥ 2.46; c-index = 0.569) and LMR (10-year OS = 60.4% for LMR ≥ 3.76 and 40.5% for LMR < 2.92; c-index = 0.568). While LMR showed the strongest association with local failure (HR = 2.16; 95% CI:1.22-3.84), PLR showed the strongest association with regional (HR = 1.98; 95% CI:1.24-3.15) and distant failure (HR = 1.67; 95% CI:1.08-2.58). CONCLUSION: Different inflammatory blood markers may be useful to identify patients at risk of local, regional, or distant recurrences who may benefit from treatment intensification or intensive surveillance programs.
Assuntos
Contagem de Células Sanguíneas , Neoplasias de Cabeça e Pescoço/sangue , Indicadores Básicos de Saúde , Mediadores da Inflamação/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Idoso , Biomarcadores Tumorais/sangue , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidadeRESUMO
This study prospectively assessed the 6-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and seven being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of the sense of smell or taste and olfactory test scores (Spearman's r = -0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had a self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of syndrome coronavirus 2 (SARS-CoV-2) infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.
Assuntos
COVID-19/complicações , COVID-19/fisiopatologia , Transtornos do Olfato/etiologia , Transtornos do Olfato/fisiopatologia , Adulto , Idoso , COVID-19/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/diagnóstico , Estudos Prospectivos , Psicofísica , SARS-CoV-2/isolamento & purificação , Autorrelato , Olfato , PaladarRESUMO
BACKGROUND: Over 50% of patients with head-and-neck squamous cell carcinoma (HNSCC) experience locoregional recurrence, which is associated with poor outcome. In the course of follow-up for patients surviving primary surgery for HNSCC, one might ask: What is the probability of recurrence in one year considering that the cancer has not yet recurred to date? MATERIALS AND METHODS: To answer this question, 979 patients surgically treated for HNSCC (i.e. cancer of the oral cavity, oropharynx, hypopharynx or larynx) between March 2004 and June 2018 were enrolled in a multicenter retrospective cohort study, followed up for death and recurrence over a 5 year period. The conditional probability of recurrence in 12 months - i.e. the probability of recurrence in the next 12 months given that, to date, the patient has not recurred - was derived from the cumulative incidence function (Aalen-Johansen method). RESULTS: Overall, the probability of recurrence was the highest during the first (17.3%) and the second years (9.6%) after surgery, declining thereafter to less than 5.0% a year thereafter. The probability of recurrence was significantly higher for stage III-IV HNSCCs than for stage I-II HNSCCs in the first year after surgery (20.4% versus 10.0%; p < 0.01), but not thereafter. This difference was most pronounced for oral cavity cancers. No significant differences were observed across different tumor sites. CONCLUSION: This dynamic evaluation of recurrence risk in patients surgically treated for HNSCC provides helpful and clinically meaningful information, which can be useful to patients in planning their future life, and to clinicians in tailoring post-treatment surveillance according to a more personalized risk stratification.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Probabilidade , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgiaRESUMO
During the last decade, the worldwide incidence of keratinocyte carcinomas (KC) has increased significantly. They are now the most common malignancy, representing approximately 30% of all cancers. The role of ultraviolet (UV) radiation as a major environmental risk factor for skin cancers is well recognized. The aim of this review is to analyse the current understanding of the nature of beta-human papillomavirus (HPV) and its association with KC and explore the implications for the management and prevention of these cancers. A comprehensive review of the literature on beta-HPV and its association with KC was undertaken, the results reported in the form of a narrative review. A subgroup of HPV that infects the mucosal epithelia of the genital tract has been firmly associated with carcinogenesis. In addition, some HPV types with cutaneous tropism have been proposed to cooperate with UV in the development of KC. The first evidence for this association was reported in 1922 in patients with epidermodysplasia verruciformis (EV). Since then, epidemiological studies have highlighted the higher risk of skin cancer in patients with EV and certain cutaneous HPV types, and in vitro studies have elucidated molecular mechanisms and transforming properties of beta-HPV. Furthermore, in vivo research conducted on transgenic mice models has shown the possible role of beta-HPV in cutaneous carcinogenesis as a co-factor with UV radiation and immunosuppression. There is good evidence supporting the role of beta-HPV in the oncogenesis of KC. The high prevalence of beta-HPV in human skin and the worldwide burden of KC makes the search for an effective vaccine relevant and worthwhile.
Assuntos
Alphapapillomavirus/fisiologia , Betapapillomavirus/fisiologia , Transformação Celular Viral , Suscetibilidade a Doenças , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias Cutâneas/etiologia , Transformação Celular Neoplásica , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversosRESUMO
PURPOSE: The aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment. METHODS: The present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM). RESULTS: Two hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51-6.90 for PFS and HR 3.41, CI 1.47-7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31-4.51 for PFS and HR = 2.40, 95% CI: 1.19-4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23-5.10 for PFS and HR = 2.60, 95% CI: 1.19-5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01-13.73) and death (HR = 5.68, 95% CI: 1.92-16.79) than low ALI and low PNI considered alone. CONCLUSIONS: Our results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.
Assuntos
Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/secundário , Pneumonia/complicações , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Idoso , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia/patologia , Prognóstico , Intervalo Livre de Progressão , Estudos RetrospectivosRESUMO
OBJECTIVES: The aim of the present study was to develop and validate the CoronaVirus-Disease-2019 (COVID-19) Questionnaire (COVID-Q), a novel symptom questionnaire specific for COVID-19 patients, to provide a comprehensive evaluation that may be helpful for physicians, and evaluate the questionnaire's performance in identifying subjects at higher risk of testing positive. MATERIALS AND METHODS: Consecutive non-hospitalised adults who underwent nasopharyngeal-throat swab for severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) detection at Treviso Hospital in March 2020, were enrolled. Subjects were divided into positive (cases) and negative (controls). All subjects answered the COVID-Q. Patients not able to answer COVID-Q because of clinical conditions were excluded. Parallel Analysis and Principal Component Analysis identified items measuring the same dimension. The Item Response Theory (IRT)-based analyses evaluated the functioning of item categories, the presence of clusters of local dependence among items, item fit within the model and model fit to the data. RESULTS: Answers obtained from 230 cases (113 males; mean age 55 years, range 20-99) and 230 controls (61 males; mean age 46 years, range 21-89) were analysed. Six components were extracted with parallel analysis: asthenia, influenza-like symptoms, ear and nose symptoms, breathing issues, throat symptoms, and anosmia/ageusia. The final IRT models retained 27 items as significant for symptom assessment. The total questionnaire's score was significantly associated with positivity to the molecular test: subjects with multiple symptoms were more likely to be affected (P < .001). Older age, male gender presence of breathing issues and anosmia/ageusia were significantly related to positivity (P < .001). Comorbidities had not a significant association with the COVID-19 diagnosis. CONCLUSION: COVID-Q could be validated since the evaluated aspects were overall significantly related to infection. The application of the questionnaire to clinical practice may help to identify subjects who are likely to be affected by COVID-19 and address them to a nasopharyngeal swab in order to achieve an early diagnosis.
Assuntos
Ageusia , COVID-19 , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste para COVID-19 , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Inquéritos e Questionários , Adulto JovemRESUMO
PURPOSE: To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. METHODS: Cross-sectional study based on ad hoc questions. RESULTS: Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (p < 0.001). CONCLUSION: Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2-positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection.
Assuntos
Disgeusia/etiologia , Transtornos do Olfato/etiologia , Distúrbios do Paladar/etiologia , Paladar/fisiologia , Betacoronavirus , COVID-19 , Busca de Comunicante , Infecções por Coronavirus , Estudos Transversais , Disgeusia/diagnóstico , Disgeusia/epidemiologia , Família , Feminino , Humanos , Masculino , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/virologia , Pandemias , Pneumonia Viral , Prevalência , SARS-CoV-2 , Olfato , Distúrbios do Paladar/diagnóstico , Distúrbios do Paladar/epidemiologia , Distúrbios do Paladar/virologiaRESUMO
Strongly associated with tobacco use, heavy alcohol consumption, and with high-risk human papillomavirus (HPV) infection, head and neck squamous cell carcinoma (HNSCC) is a frequently lethal, heterogeneous disease whose pathogenesis is a multistep and multifactorial process involving genetic and epigenetic events. The majority of HNSCC patients present with locoregional advanced stage disease and are treated with combined modality strategies that can markedly impair quality of life and elicit unpredictable results. A large fraction of those who undergo locoregional treatment and achieve a complete response later develop locoregional recurrences or second field tumors. Biomarkers that are thus able to stratify risk and enable clinicians to tailor treatment plans and to personalize post-therapeutic surveillance strategies are highly desirable. To date, only HPV status is considered a reliable independent predictor of treatment response and survival in patients with HNSCC arising from the oropharyngeal site. Recent studies suggest that telomere attrition, which may be an early event in human carcinogenesis, and telomerase activation, which is detected in up to 90 % of malignancies, could be potential markers of cancer risk and disease outcome. This review examines the current state of knowledge on and discusses the implications linked to telomere dysfunction and telomerase activation in the development and clinical outcome of HNSCC.
Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Telomerase/metabolismo , Telômero/genética , Animais , Biomarcadores Tumorais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Variação Genética , Instabilidade Genômica , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/patologia , Camundongos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Homeostase do TelômeroRESUMO
BACKGROUND: The prevalence and incidence of oropharyngeal squamous cell carcinomas (OPSCCs) driven by human papillomavirus (HPV) infection are increasing worldwide, being higher in high-income countries. However, data from Italy are scanty. p16INK4a overexpression is the standard in determining HPV-driven carcinogenesis, but disease prevalence impacts on its positive predictive value. METHODS: This is a multicenter retrospective study enrolling 390 consecutive patients aged ≥18 years, diagnosed with pathologically confirmed OPSCC in Northeastern Italy between 2000 and 2022. High-risk HPV-DNA and p16INK4a status were retrieved from medical records or evaluated in formalin-fixed paraffin-embedded specimens. A tumor was defined as HPV-driven when double positive for high-risk HPV-DNA and p16INK4a overexpression. RESULTS: Overall, 125 cases (32%) were HPV-driven, with a significant upward temporal trend from 12% in 2000-2006 to 50% in 2019-2022. The prevalence of HPV-driven cancer of the tonsil and base of the tongue increased up to 59%, whereas it remained below 10% in other subsites. Consequently, the p16INK4a positive predictive value was 89% for the former and 29% for the latter. CONCLUSIONS: The prevalence of HPV-driven OPSCC continued to increase, even in the most recent period. When using p16INK4a overexpression as a surrogate marker of transforming HPV infection, each institution should consider the subsite-specific prevalence rates of HPV-driven OPSCC as these significantly impact on its positive predictive value.
RESUMO
At this juncture, autofluorescence and narrow-band imaging have resurfaced in the medicine arena in parallel with current technology advancement. The emergence of newly developed optical instrumentation in addition to the discovery of new fluorescence biomolecules have contributed to a refined management of diseases and tumors, especially in the management of upper aerodigestive tract tumors. The advancement in multispectral imaging and micro-endoscopy has also escalated the trends further in the setting of the management of this tumor, in order to gain not only the best treatment outcomes but also facilitate early tumor diagnosis. This includes the usage of autofluorescence endoscopy for screening, diagnosis and treatment of this tumor. This is crucial, as microtumoral deposit at the periphery of the gross tumor can be only assessed via an enhanced endoscopy and even more precisely with autofluorescence endoscopic techniques. Overall, with this new technique, optimum management can be achieved for these patients. Hence, the treatment outcomes can be improved and patients are able to attain better prognosis and survival.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Lesões Pré-Cancerosas , Humanos , Endoscopia Gastrointestinal , Carcinoma de Células Escamosas/patologia , Lesões Pré-Cancerosas/diagnóstico , Diagnóstico Precoce , Neoplasias de Cabeça e Pescoço/diagnóstico por imagemRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICI) are approved for treatment of recurrent or metastatic oropharyngeal head and neck squamous cell carcinoma in the first- and second-line settings. However, only 15-20% of patients benefit from this treatment, a feature increasingly ascribed to the peculiar characteristics of the tumor immune microenvironment (TIME). METHODS: Immune-related gene expression profiling (GEP) and multiplex immunofluorescence (mIF) including spatial proximity analysis, were used to characterize the TIME of 39 treatment-naïve oropharyngeal squamous cell carcinomas (OPSCC) and the corresponding lymph node metastases. GEP and mIF results were correlated with disease-free survival (DFS). HPV-positive tumors disclosed a stronger activation of several immune signalling pathways, as well as a higher expression of genes related to total tumor-infiltrating lymphocytes, CD8 T cells, cytotoxic cells and exhausted CD8 cells, than HPV-negative patients. Accordingly, mIF revealed that HPV-positive lesions were heavily infiltrated as compared to HPV-negative counterparts, with a higher density of T cells and checkpoint molecules. CD8+ T cells appeared in closer proximity to tumor cells, CD163+ macrophages and FoxP3+ cells in HPV-positive primary tumors, and related metastases. In HPV-positive lesions, PD-L1 expression was increased as compared to HPV-negative samples, and PD-L1+ tumor cells and macrophages were closer to PD-1+ cytotoxic T lymphocytes. Considering the whole cohort, a positive correlation was observed between DFS and higher levels of activating immune signatures and T cell responses, higher density of PD-1+ T cells and their closer proximity to tumor cells or PD-L1+ macrophages. HPV-positive patients with higher infiltration of T cells and macrophages had a longer DFS, while CD163+ macrophages had a negative role in prognosis of HPV-negative patients. CONCLUSIONS: Our results suggest that checkpoint expression may reflect an ongoing antitumor immune response. Thus, these observations provide the rationale for the incorporation of ICI in the loco-regional therapy strategies for patients with heavily infiltrated treatment-naïve OPSCC, and for the combination of ICI with tumor-specific T cell response inducers or TAM modulators for the "cold" OPSCC counterparts.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Antígeno B7-H1/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Fatores de Transcrição Forkhead , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/metabolismo , Infecções por Papillomavirus/complicações , Receptor de Morte Celular Programada 1/metabolismo , Análise Espacial , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Microambiente TumoralRESUMO
BACKGROUND AND PURPOSE: Currently, human papillomavirus (HPV) positivity represents a strong prognostic factor for both reduced risk of relapse and improved survival in patients with oropharyngeal squamous cell carcinoma (OPSCC). However, a subset of HPV-positive OPSCC patients still experience poor outcomes. Furthermore, HPV-negative OPSCC patients, who have an even higher risk of relapse, are still lacking suitable prognostic biomarkers for clinical outcome. Here, we evaluated the prognostic value of LINE-1 methylation level in OPSCC patients and further addressed the relationship between LINE-1 methylation status and p53 protein expression as well as genome-wide/gene-specific DNA methylation. RESULTS: In this study, DNA was extracted from 163 formalin-fixed paraffin-embedded tissue samples retrospectively collected from stage III-IVB OPSCC patients managed with curative intent with up-front treatment. Quantitative methylation-specific PCR revealed that LINE-1 hypomethylation was directly associated with poor prognosis (5-year overall survival-OS: 28.1% for LINE-1 methylation < 35% vs. 69.1% for ≥ 55%; p < 0.0001). When LINE-1 methylation was dichotomized as < 55% versus ≥ 55%, interaction with HPV16 emerged: compared with hypermethylated HPV16-positive patients, subjects with hypomethylated HPV16-negative OPSCC reported an adjusted higher risk of death (HR 4.83, 95% CI 2.24-10.38) and progression (HR 4.54, 95% CI 2.18-9.48). Tumor protein p53 (TP53) gene is often mutated and overexpressed in HPV-negative OPSCC. Since p53 has been reported to repress LINE-1 promoter, we then analyzed the association between p53 protein expression and LINE-1 methylation levels. Following p53 immunohistochemistry, results indicated that among HPV16-negative patients with p53 ≥ 50%, LINE-1 methylation levels declined and remained stable at approximately 43%; any HPV16-positive patient reported p53 ≥ 50%. Finally, DNA methylation analysis demonstrated that genome-wide average methylation level at cytosine-phosphate-guanine sites was significantly lower in HPV16-negative OPSCC patients who relapsed within two years. The subsequent integrative analysis of gene expression and DNA methylation identified 20 up-regulated/hypomethylated genes in relapsed patients, and most of them contained LINE-1 elements in their promoter sequences. CONCLUSIONS: Evaluation of the methylation level of LINE-1 may help in identifying the subset of OPSCC patients with bad prognosis regardless of their HPV status. Aberrant LINE-1 hypomethylation might occur along with TP53 mutations and lead to altered gene expression in OPSCC.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Infecções por Papillomavirus/complicações , Elementos Nucleotídeos Longos e Dispersos , Metilação de DNA , Estudos Retrospectivos , Recidiva Local de Neoplasia/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Neoplasias de Cabeça e Pescoço/genéticaRESUMO
Objective: The prognostic significance of the resection margins is still subject of conflicting opinions. The purpose of this paper is to report the results of a study on the margins in carcinoma of the oral cavity, oro-hypopharynx and larynx. Methods: A multicentre prospective study was carried out between 2015 and 2018 with the participation of 10 Italian reference hospitals. The primary objective was to evaluate local control in patients with well-defined clinical characteristics and comprehensive histopathological information. Results: During the study period, 455 patients were enrolled; the minimum follow-up was 2 years. Previous treatment, grading and fresh specimen examination were identified as risk factors for local control in multivariate analysis. On the basis of these results, it seems possible to delineate "risk profiles" for different oncological outcomes. Discussion: The prognostic significance of the margins is reduced, and other risk factors emerge, which require diversified treatment and follow-up. Conclusions: Multidisciplinary treatment with adjuvant therapy, if indicated, reduces the prognostic importance of margins. Collaboration with a pathologist is an additional favourable prognostic factor and quality indicator.An appendix with literature review is present in the online version.
Assuntos
Carcinoma de Células Escamosas , Laringe , Carcinoma de Células Escamosas/cirurgia , Humanos , Hipofaringe/patologia , Laringe/patologia , Margens de Excisão , Boca , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Severe acute respiratory infection Coronavirus 2 (SARS-CoV-2) infection has spread all over the world since December 2019. Treatment of the syndrome represents an important challenge for all physicians. Spread prevention relies on a correct diagnosis which is performed with nasopharyngeal swabs. OBJECTIVE: To describe the proper execution of the swab with a few simple steps. METHODS: Figures and video recording. RESULTS: A few simple steps are presented within this paper in order to perform easily nasopharyngeal swab for SARS-Cov-2 diagnosis and for other possible infectious diseases of the airways tract. CONCLUSIONS AND IMPLICATION FOR NURSING: Nasopharyngeal swab may be performed in an easier way than usually thought. This method may also be used for any other microorganism detection. By following simple steps, a correct diagnosis can easily be obtained.
RESUMO
The pandemic caused by SARS-CoV2 has stressed health care systems worldwide. The high volume of patients, combined with an increased need for intensive care and potential transmission, has forced reorganization of hospitals and care delivery models. In this article, are presented approaches to minimize risk to Otolaryngologists during their patients infected with COVID-19 care. We performed a narrative literature review among PubMed, Scopus and Web of Science electronic databases, searching for studies on SARS-CoV2 and Risk Management. Standard operating procedures have been adapted both for facilities and for health care workers, including the development of well-defined and segregated patient care areas for treating those affected by COVID-19. Personal protective equipment (PPEs) availability and adequate healthcare providers training on their use should be ensured. Preventive measures are especially important in Otolaryngology-Head and Neck Surgery, as the exposure to saliva suspensions, droplets and aerosols are increased in the upper aero-digestive tract routine examination. Morever, the frequent invasive procedures, such as laryngoscopy, intubation or tracheotomy placement and care, represent a high risk of contracting COVID-19.
Assuntos
COVID-19/prevenção & controle , Otorrinolaringologistas , Gestão de Riscos , SARS-CoV-2 , Humanos , Equipamento de Proteção Individual , TraqueostomiaRESUMO
OBJECTIVE: Mean corpuscular volume (MCV) has been shown in to be a reliable prognostic marker in other cancers; however, no evidence exists on its use in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate the association between MCV, hemoglobin, platelet count and albumin concentration, and survival in stage III/IVA-B HNSCC treated with concurrent chemoradiotherapy. STUDY DESIGN: Retrospective cohort study. METHODS: In this multicenter retrospective study, we analyzed MCV, platelet count, hemoglobin concentration, and albumin concentration in peripheral blood samples from 260 patients with HNSCC undergoing organ preservation treatment with curative intent at the time of diagnosis. We then analyzed survival outcomes after accounting for confounders using multivariate analysis. RESULTS: After adjustment for potential confounders, patients with low hemoglobin had a 3.3-fold higher risk of death (95% confidence interval [CI]: 2.26-4.81) than those with normal hemoglobin. Patients with an elevated MCV had a 1.54-fold higher risk of death (95% CI: 1.06-2.24), independent of site, stage, and human papillomavirus status. Interestingly, the effect of MCV on overall and progression-free survival was limited to those with a normal pretreatment hemoglobin. We identified no associations between pretreatment platelet count or albumin concentration and survival. CONCLUSION: These findings suggest that pretreatment anemia and macrocytosis are independent predictors of lower overall and progression-free survival in HNSCC patients undergoing organ preservation treatment. LEVEL OF EVIDENCE: III Laryngoscope, 131:E836-E843, 2021.
Assuntos
Índices de Eritrócitos , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Idoso , Quimiorradioterapia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Hemoglobinas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Contagem de Plaquetas , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Albumina Sérica/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVES: Patients with coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may present with a wide range of symptoms. In this paper, a detailed characterisation of mild-to-moderate ear, nose nd throat (ENT) symptoms is presented with the aim of recognising the disease early to help reduce further spread and progression. METHODS: A total of 230 cases testing positive for SARS-CoV-2 and 134 negative controls were recruited for a case-control analysis. Symptoms were analysed using the Acute Respiratory Tract Infections Questionnaire, while other symptoms were investigated by ad hoc questions. RESULTS: Among the study samples (n = 364), 149 were males and 215 were females with age ranging from 20 to 89 years (mean 52.3). Four main groups of symptoms were obtained: influenza-like symptoms, ENT-symptoms, breathing issues and asthenia-related symptoms, representing 72%, 69%, 64% and 53% of overall referred clinical manifestations, respectively. ENT symptoms, breathing issues and influenza-like symptoms were associated with positivity to SARS-CoV-2, whereas asthenia-related symptoms did not show a significant association with SARS-CoV-2 infection after controlling for other symptoms, comorbidities and demographic characteristics. CONCLUSIONS: ENT symptoms are equally represented with influenza-like ones as presenting symptoms of COVID-19. Patients with ENT symptoms should be investigated for early identification and prevention of SARS-CoV-2 spread.
Assuntos
COVID-19/complicações , Otorrinolaringopatias/diagnóstico , Otorrinolaringopatias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: At present, the prognostic significance of programmed cell death receptor ligand 1 (PD-L1) expression in oropharyngeal squamous cell carcinoma (OPSCC) patients is still controversial. In this study, we aim to synthesize relevant studies that have assessed the prognostic value of PD-L1 in patients with primary OPSCC treated according to the current standard-of-care. METHODS: A systematic search of Medline/PubMed, Cochrane, Embase, Web of Science, and Scopus was conducted to define the prognostic role of PD-L1 expression in OPSCC. All studies published before July 31, 2021 were screened. Summary hazard ratios (sHR) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: A total of 1522 OPSCC patients from 12 studies were included. PD-L1 expression in OPSCC tumor cells (TCs) was significantly associated with longer overall survival (sHR=0.63, 95% CI 0.50-0.79), and progression-free survival (sHR=0.62, 95% CI 0.49-0.79). A benefit in survival was also observed in PD-L1-positive OPSCC patients who underwent surgery (sHR=0.34, 95% CI 0.18-0.65). Finally, although PD-L1-positive expression was related to better outcomes both in HPV-negative and HPV-positive OPSCC, the difference reached the statistical significance only in the HPV-positive subgroup (sHR=0.37, 95% CI 0.19-0.73). No heterogeneity emerged between studies for all considered outcomes, with I 2 ranging from 0% for progression-free survival to 11% for overall survival. CONCLUSIONS: PD-L1 expression on TCs associated with improved survival in OPSCC. In particular, HPV-positive OPSCC most benefited from PD-L1 expression when compared to the PD-L1 negative counterpart. Thus, PD-L1 might represent a useful biomarker to stratify prognosis in OPSCC in addition to HPV status.