How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

Depth of Invasion Assessment in Laryngeal Glottic Carcinoma: A Preoperative Imaging Approach for Prognostication.

OBJECTIVE: The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging. METHODS: The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival. RESULTS: Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis. CONCLUSION: Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3230-3237, 2024.

Contact Endoscopy - Narrow Band Imaging (CE-NBI) data set for laryngeal lesion assessment.

The endoscopic examination of subepithelial vascular patterns within the vocal fold is crucial for clinicians seeking to distinguish between benign lesions and laryngeal cancer. Among innovative techniques, Contact Endoscopy combined with Narrow Band Imaging (CE-NBI) offers real-time visualization of these vascular structures. Despite the advent of CE-NBI, concerns have arisen regarding the subjective interpretation of its images. As a result, several computer-based solutions have been developed to address this issue. This study introduces the CE-NBI data set, the first publicly accessible data set that features enhanced and magnified visualizations of subepithelial blood vessels within the vocal fold. This data set encompasses 11144 images from 210 adult patients with pathological vocal fold conditions, where CE-NBI images are annotated using three distinct label categories. The data set has proven invaluable for numerous clinical assessments geared toward diagnosing laryngeal cancer using Optical Biopsy. Furthermore, given its versatility for various image analysis tasks, we have devised and implemented diverse image classification scenarios using Machine Learning (ML) approaches to address critical clinical challenges in assessing laryngeal lesions.

Diagnostic Assessment (Imaging) and Staging of Laryngeal Cancer.

Diagnosis of larynx cancer relies on a detailed history and physical and objective assessment with endoscopy and imaging. Endoscopy is needed to assess for vocal fold function that directly affects staging. Computed tomography and MRI can be used to assess for tumor extent in relation to intra- and extra-laryngeal structures, especially paraglottic and pre-epiglottic space involvement as well as cartilage invasion. Accurate staging is critical for subsequent treatment decision-making regarding larynx preservation.

A systematic review on efficacy, safety and cost-effectiveness of office-based laryngeal biopsy.

OBJECTIVE: Laryngeal cancer is the second most prevalent head and neck malignancy in the USA. With recent advances in technology, this procedure is increasingly performed under local anaesthesia. This study aimed to identify the efficacy, safety and cost-effectiveness of laryngeal biopsy in out-patients by conducting a systematic review. METHOD: A literature search was conducted using PubMed, Medline, Google Scholar and Embase over a 20-year period. Inclusion criteria were: studies performed on out-patient diagnostic biopsy procedures of the larynx. Exclusion criteria included all therapeutic procedures. The outcome measures were sensitivity and specificity, complication rate and cost-savings. RESULTS: Thirty-five studies were included in the analysis. The sensitivity and specificity varied from 60 to 100 per cent with a low complication rate and cost savings. CONCLUSION: Office-based laryngeal biopsies are increasingly used in the diagnosis of laryngeal cancers, resulting in earlier diagnosis and commencement of treatment. The barrier to undertaking this procedure is low sensitivity.

Assessment of immunomodulation and regulation of cell cycle in epithelium and stroma after Cidofovir injection in patients with recurrent respiratory papillomatosis-Pilot study.

Recurrent respiratory papillomatosis is strictly connected with human papillomavirus (HPV) infection of the epithelium of the upper respiratory tract. The main treatment of lesions located in the larynx or lower pharynx includes microsurgical excision by using a CO2 laser. To decrease the amount of surgical procedures gain in importance combined therapy with antiviral agents. The aim of this study was to investigate the effect of the intralesional application of Cidofovir on the tissue of laryngeal papillomas. We have shown that simultaneous microsurgery with adjuvant therapy of Cidofovir reduces chronic inflammation (by measuring the expression of CD4 and CD8 in tissue samples), cell proliferation, and regulates the cell cycle of HPV-infected cells by reducing the expression of p53 and p63 proteins. In addition, this strategy reduces the multiple surgical procedures and regrowth of the pathology.

Treatment outcomes and cost comparisons for older adults with T4 laryngeal squamous cell cancer.

BACKGROUND: To evaluate treatment modalities of T4 larynx cancer in older adults using SEER-Medicare. METHODS: The database was queried for patients aged 66 and older with nonmetastatic T4 laryngeal squamous cell cancer from 2006 to 2015. Treatment modalities compared were surgery plus chemoradiation (SCR), surgery plus radiation (SR), chemoradiation (CR), surgery (S), and radiation (R). Multivariate analysis and Kaplan-Meier methods were used to explore the relationship of treatment modality and survival. Total cancer-related costs were calculated. RESULTS: A total of 438 patients met inclusion criteria. Patients receiving CR or SR had similar CSS to SCR (HR 1.36 and HR 1.24, respectively). Those receiving S (HR 2.00) or R (HR 2.41) had significantly worse CSS. Similar findings were observed for OS. Cancer care-related costs were not significantly different but highest in SCR ($162215) and lowest in R ($121421). CONCLUSION: Older patients with T4 larynx cancer had similar survival rates when treated with CR, SR, and SCR. Average total health care costs were not significantly different between modalities. Patients not eligible for triple-modality could consider these other treatment options.

Ultrasonography for masses of the pharynx and larynx and assessment of laryngeal squamous cell carcinoma.

OBJECTIVE: To evaluate the ultrasonography (US) characteristics of pharyngeal/laryngeal masses and the role of US in the assessment of laryngeal squamous cell carcinoma (LSCC). METHODS: This study enrolled patients who underwent US for evaluation of pharyngeal/laryngeal masses between 2018 and 2021. Characteristics of pharyngeal/laryngeal masses and subsite invasion in cases of LSCC were evaluated using US. RESULTS: Forty-six patients with pharyngeal (n = 22) /laryngeal (n = 24) masses were enrolled. The pathological results were benign and malignant in 7 (15.2%) and 39 (84.8%) patients, respectively. Malignant masses were significantly associated with US characteristics of heterogeneity (P = 0.002), irregular/speculated margin (P < 0.001), and increased internal vascularity (P = 0.014) compared with benign masses. In patients with LSCC, the detection rate of US for subsites invasion, including that of the anterior commissure, paraglottic space, outer cortex of the thyroid cartilage, cricoid cartilage, and extralaryngeal soft tissue, was similar to that of computed tomography (CT). Although the difference was not statistically significant, US more frequently demonstrated invasion of the inner cortex of the thyroid cartilage than CT (40.9% vs. 22.7%; P = 0.195). US and CT had a concordance rate of 81% (18 of 22 patients) in determining the tumour stage of the lesions. CONCLUSION: US could facilitate differentiation between benign and malignant masses of the pharynx and larynx in selective patients and has a possible role in the assessment of LSCC.

Assessment of Early Stage Glottic Cancer Depth of Resection After Transoral Laser Cordectomy.

OBJECTIVE: Surgeons generally determine depth of resection during transoral laser cordectomy by visual inspection of the surgical field. Our aim was to examine the correlation between early glottic cancer depth of resection as reported by surgeons in the operation report and depth of resection defined by pathology specimens, using various staining techniques intended to differentiate between the distinct vocal fold layers based on particular collagen deposition. STUDY DESIGN: Retrospective study. SETTING: A voice and swallowing clinic at a tertiary referral hospital. METHODS: We compared depth of cordectomy assessed intraoperatively by surgeons and by pathologists using Picrosirius red stain and collagen I immunohistochemistry stain in 32 patients who underwent transoral laser cordectomy for early glottic cancer. RESULTS: For type I, II, and III cordectomy, the respective proportions of patients were 14 (47%), 9 (30%), and 7 (23%) according to surgeons' estimations; 2 (6%), 17 (55%), and 12 (39%) according to Picrosirius red stain; and 3 (11%), 12 (44%), and 12 (45%) according to immunohistochemistry for collagen I. CONCLUSION: Surgeons' reported depth of resection did not correlate with depth of resection established by either staining technique. Determining depth of resection necessitates special stains, which should help in the clinical assessment of cordectomy type.

Reduction in healthcare services during the COVID-19 pandemic: Patient screening based on symptoms is an effective strategy for avoiding delayed laryngeal cancer diagnosis.

OBJECTIVE: Restriction in healthcare services during the COVID-19 pandemic caused delays in the diagnosis and treatment of several diseases. To overcome the risk of missed diagnosis of head and neck cancers, before deleting the scheduled appointments, we have introduced a selection of the patients by examining the clinical presenting issue and previous medical history. The aim of this study is to show the effects of the abovementioned strategy on the diagnosis and management of laryngeal cancer. METHODS: Data were extracted from the Hospital software regarding the new diagnosis of laryngeal SCC in the periods from March 2020 to December 2020 during the pandemic (study group) and from March 2019 to December 2019 (control group) were collected. Data were compared regarding: TNM stage, time from first medical examination to histological diagnosis (Time-1), and time form histological diagnosis to beginning of treatments (Time-2). RESULTS: The final study group was composed by 19 laryngeal cancers, the control group by 25 cases. No significant differences were found in the tumour stage between the groups. In the study group, Time-1 was shorter (24 days versus 43 days, p = 0.012), while Time-2 in surgically-treated patients was longer (20 days versus 9 days, p = 0.012). CONCLUSION: During the pandemic, there was a dramatic lack of medical and nurse staff needed for surgical procedures. As consequence, the time between the diagnosis of malignancy and surgical treatment increased. In our unit, an efficient patient selection strategy to reschedule medical appointments avoided a dangerous shift toward higher laryngeal cancer stages.

Does insurance type influence overall survival in patients with laryngeal squamous cell carcinoma?

OBJECTIVE: Patients with head and neck cancer with Medicaid or no insurance present at a more advanced stage and have lower survival. This study is one of the first to examine the relationship between specific insurance types and overall survival for laryngeal squamous cell carcinoma patients. STUDY DESIGN: Retrospective chart review. SETTING: Henry Ford Cancer Institute. SUBJECTS AND METHODS: A retrospective database review was performed using the Henry Ford Virtual Data Warehouse Tumor Registry. Six hundred and fifty patients diagnosed with laryngeal squamous cell carcinoma were identified. Insurance groups analyzed were fee for service, health maintenance organization, Henry Ford Medical Group - a managed care type insurance, Medicare and Medicaid/uninsured. Cox proportional hazards and Kaplan-Meier curves were generated to analyze overall survival and display survival differences respectively. RESULTS: The uninsured group had the lowest median survival time of 29.8 months (95% CI: 20.3-44.8) and the highest HR of 1.85 (95% CI 1.16-2.93) as compared to the HMO group at p < 0.001. Patients with fee for service insurance had longer overall survival compared to the other insurance types. Patients with fee for service insurance also had a high proportion of patients with advanced stage disease, but a younger mean age. Henry Ford Medical Group had a higher mean age and no statistically significant difference in survival when compared to fee for service. (p = 0.999) After controlling for socioeconomic status, insurance type remains a significant predictor of overall survival. CONCLUSIONS: Fee for service had the highest overall survival of the different insurance types, but it was only statistically significant when compared to the Medicaid/uninsured group.

Feasibility of intraoperative assessment of safe surgical margins during laryngectomy with confocal laser endomicroscopy: A pilot study.

OBJECTIVE: This pilot study aimed to assess the feasibility of intraoperative assessment of safe margins with Confocal Laser Endomicroscopy (CLE) during planned partial or total laryngectomy. METHODS: Eight patients with confirmed larynx squamous cell carcinoma (SCC) and planned partial or total laryngectomy were included in this study in March 2020. Two head and neck surgeons and one pathologist were asked to classify carcinoma or healthy epithelium in a sample of 94 representative sequences (5.640 images), blinded to the histological results (H&E staining). RESULTS: Healthy mucosa areas showed epithelium with cells of uniform size and shape with distinct cytoplasmic membranes and regular vessel architecture. CLE optical biopsy of SCC demonstrated a disorganized arrangement of variable cellular morphology. We calculated an accuracy, sensitivity, specificity, PPV, and NPV of 80.1%, 72.3%, 87.9%, 85.7%, and 76.1%, respectively. A distinct transition between healthy appearing tissue and suspicious lesions could also be detected. CONCLUSION: CLE can be easily integrated into the intraoperative setting, generate real-time, in-vivo microscopic images of the larynx for evaluation and demarcation of cancer. If validated in further studies, CLE could eventually contribute to a less radical approach by enabling a more precise evaluation of the cancer margin.

Gender and race interact to influence survival disparities in head and neck cancer.

Gender and race disparities in head and neck squamous cell carcinoma (HSNCC) survival are independently well documented, but no prior studies have examined the joint effect of these factors on HSNCC outcomes. We aim to comprehensively estimate the effect of gender and race on overall survival in HNSCC. We constructed a retrospective cohort from the National Cancer Database for primary HNSCC of the larynx, hypopharynx, oral cavity, and oropharynx from 2010 to 2015. We used Kaplan-Meier curves and Cox proportional hazards regressions to calculate hazard ratios adjusting for treatment type, age, insurance, staging classifications, and comorbidities. Oral cavity cancer was significantly more common among Hispanic and White females compared to other sites. Female non-oropharyngeal HNSCC cases had better five-year overall survival than males (56.3% versus 54.4%, respectively), though Black females (52.8%) had poorer survival than both White (56.2%) and Hispanic (57.9%) males. There were significant differences in oropharyngeal cancer by HPV status. Notably, Black females with HPV-positive oropharyngeal OPSCC had far worse survival than any other race and gender group. These results persisted even when adjusting for potential mediating factors. Clearly gender is a significant prognosticator for HNSCC and has meaningful interactions with race. The distinct site distributions across gender and race reveal important insights into HNSCC among females. Taking into account these gender disparities while considering race is essential to providing appropriate care to head and neck patients and accurately counselling these individuals on prognosis and outcomes.

Time and Cost of Ultrasound-Guided Fine-Needle Aspiration Biopsy/Core-Needle Biopsy for Primary Laryngohypopharyngeal Squamous Cell Carcinoma.

OBJECTIVES: This study aimed to evaluate benefits in terms of time and cost of percutaneous ultrasound-guided fine-needle aspiration biopsy/core-needle biopsy (US-FNAB/CNB) for the diagnosis of primary laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) in comparison with direct laryngoscopic biopsy (DLB) under general anesthesia. STUDY DESIGN: Retrospective case-control study. SETTING: Single operator of a single center. SUBJECTS AND METHODS: From 2018 to 2019, 28 patients who underwent percutaneous US-FNAB/CNB for the diagnosis of untreated LHSCC were enrolled. All US-FNAB/CNBs were performed in the outpatient department by a single head and neck surgeon. Their results were compared with those of 27 patients who underwent DLB under general anesthesia. RESULTS: No major complications occurred in the US-FNAB/CNB and DLB groups. Time to biopsy, time to pathologic diagnosis, and time to treatment initiation in the US-FNAB/CNB and DLB groups were 0 and 14 days (P < .001), 7 and 20 days (P < .001), and 24 and 35 days (P = .001), respectively. Procedure-related costs were $368.5 and $981.0 in the US-FNAB/CNB and DLB groups (P < .001). CONCLUSIONS: US-FNAB/CNB offers true benefits in terms of time and cost over those given by conventional DLB for diagnosis of LHSCC in indicated patients.

Contrast-enhanced ultrasound for the preoperative assessment of laryngeal carcinoma: a preliminary study.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is considered an attractive imaging technique to evaluate tumor microcirculation. However, the validity of CEUS for assessing laryngeal carcinoma is unclear. PURPOSE: To compare the performance of CEUS with conventional US and contrast-enhanced computed tomography (CECT) in the diagnosis and preoperative T-staging of laryngeal carcinoma. MATERIAL AND METHODS: Forty-one consecutive patients with laryngeal carcinoma underwent conventional high-frequency US, CEUS, and CECT before surgery. The CEUS characteristics of laryngeal carcinoma were recorded. The imaging findings of CEUS and conventional US were compared with CECT findings and the postoperative pathological examination. RESULTS: CEUS showed hyperenhancement in 38 cases and isoenhancement in three cases. Homogeneous distribution of contrast agent was found in 20 cases and heterogeneous distribution in 21 cases, of which 16 cases showed local perfusion defects. In the enhanced phase, rapid entry was observed in 37 cases, synchronous entry was observed in two cases, and slow entry was observed in two cases. Rapid exit was observed in 25 cases and slow exit was observed in 16 cases. The pretherapeutic T-staging accuracy was not significantly different between conventional US, CEUS, and CECT (P ≥ 0.500). A high sensitivity and specificity were achieved by CEUS in the evaluation of involvement of thyroid cartilage. CONCLUSION: Compared with conventional US and CECT, CEUS has a reliable initial T-staging accuracy and diagnostic properties for detecting laryngeal cartilage invasion.

Cost-effectiveness analysis of voice rehabilitation for patients with laryngeal cancer: a randomized controlled study.

INTRODUCTION: Voice problems are common following radiotherapy for laryngeal cancer. Few studies exist covering the effect of voice rehabilitation, and no previous studies exist regarding the cost of said rehabilitation. This randomized controlled study aimed to analyze the cost-effectiveness of voice rehabilitation after radiotherapy for patients with laryngeal cancer. MATERIAL AND METHODS: A total of 66 patients with laryngeal cancer with follow-up data 12 months post-radiotherapy were included. Patients were randomized into receiving either voice rehabilitation (n = 32) or no voice rehabilitation (n = 34). The patient outcome was measured as quality-adjusted life years (QALYs). The index range between 0 and 1, where 0 equals death and 1 represents perfect health. The QALYs were assessed with the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30 mapped to EuroQoL 5 Dimension values. The cost of rehabilitation and other healthcare visits was derived from hospital systems. The patients reported the total amount of sick leave days during the first 12 months following radiotherapy. The cost-effectiveness of the voice rehabilitation was compared with no rehabilitation intervention based on the incremental cost-effectiveness ratio. RESULTS: The cost per gained QALY with voice rehabilitation compared to no rehabilitation from a societal perspective was - 27,594 € (SEK - 250,852) which indicates that the voice rehabilitation is a cost-saving alternative compared to no rehabilitation due to lower costs and a slightly better health outcome. From a healthcare perspective, the voice rehabilitation indicates a cost 60,800 € (SEK 552,725) per gained QALY. CONCLUSION: From a societal perspective, i.e., including the costs of production loss, voice rehabilitation compared to no voice rehabilitation following radiotherapy for laryngeal cancer seems to be cost-saving. When analyzing only the healthcare costs in relation to health outcomes, voice rehabilitation indicates an incremental cost of 60,800 € per gained QALY, which is just above the threshold of the maximum willingness to pay level.

Evaluation of narrow band imaging in the assessment of laryngeal granuloma.

Laryngeal granulomas belong to common complications following trans-oral laser microsurgery (TLM). The aim of this study was to evaluate NBI in the differentiation between granuloma-like lesions and local tumor recurrence. 154 consecutive patients after TLM due to early laryngeal cancer were enrolled. In the group, a monthly follow-up including NBI endoscopy was performed. Moderate and severe dysplasia, carcinoma in situ and invasive cancer were defined as positive histology, laryngeal granuloma and other benign laryngeal lesions as negative histology and premalignant lesions as suspicious histology. In 47/154 (31%) cases, granuloma-like lesion (GLL) was found. Patients with GLL were divided into two groups based on the NBI classification. In all patients, the microvascular pattern in NBI was compared with the final histology. In group A, with suspicious, perpendicular vessels, 13/13 (100%) samples were positive. In group B, with normal vascular pattern 3/34 (9%) samples were positive and 31/34 (91%) samples were negative. There was a significant correlation between the positive NBI vascular pattern and the final histology (p = 0.00001). Sensitivity, specificity, accuracy of NBI were as follows: 81%, 100%, 94%, respectively.Based on our results, NBI can reliably differentiate between postoperative laryngeal granuloma and local tumor recurrence. In such a manner, this method is very helpful in the follow-up of tumor patients.

Influence of Socioeconomic Status on Stage at Presentation of Laryngeal Cancer in the United States.

OBJECTIVE: Identify socioeconomic predictors of stage at diagnosis of laryngeal cancer in the United States. STUDY DESIGN: Retrospective analysis of the North American Association of Central Cancer Registries' Incidence Data-Cancers in North America Deluxe Analytic File for expanded races. SETTING: All centers reporting to the US Centers for Disease Control and Prevention's National Program of Cancer Registries. SUBJECTS AND METHODS: All cases of laryngeal cancer in adult patients from 2005 to 2013 were reviewed. Ordinal logistic regression models were used to evaluate odd ratios (ORs) for socioeconomic indicators potentially predictive of advancing American Joint Committee on Cancer stage at diagnosis. RESULTS: A total of 72,472 patients were identified and included. Analysis revealed significant correlation between advanced stage at diagnosis and: Medicaid insurance, lack of insurance, female sex, older age, black race, and certain states of residence. The strongest predictor of advanced stage was lack of insurance (OR, 2.212; P < .001; 95% CI, 2.035-2.406). The strongest protective factor was residing in the state of Utah (OR, 0.571; P < .001; 95% CI, 0.536-0.609). Once adjusted for regional price and wage disparities, relative income was not a significant predictor of stage at presentation across multiple analyses. CONCLUSION: Multiple socioeconomic factors were predictive of severity of disease at presentation of laryngeal cancer in the United States. This study demonstrated that insurance type was strongly predictive, whereas relative income had surprisingly little influence.

Assessment of tumor-associated immune cells in laryngeal squamous cell carcinoma.

PURPOSE: This study investigated the characteristics of tumor-associated immune cells (TAICs) in laryngeal squamous cell carcinoma (LSCC) and their correlation with clinicopathological variables. METHODS: The immune cell infiltrates of 71 specimens of stages I-IV LSCC were examined. The density of TAICs expressing CD3, CD4, CD8, CD68, and CD163 was assessed using immunohistochemical staining and image analysis in peritumoral and intratumoral regions. RESULTS: Higher densities of CD3+ and CD8+ cell and lower densities of CD68+ and CD163+ cell infiltrations were found in early tumor stages than in late tumor stages. A higher percentage of patients with strong CD3+ and CD8+ immune cell infiltration and weak CD68+ cell infiltration in both tumor regions presented with T1 stage tumors compared with T4 stage tumors. Further, strong CD68+ cells infiltration in both regions was observed in a greater number of patients who had a relapse, while a weak CD3+ cells infiltration in both regions was found in a greater number of patients with nodal lymphatic metastasis. The univariate analysis showed that a high density of peritumoral CD3+ and CD8+ immune cells in both regions was significantly associated with a favorable overall survival (OS) (P = 0.004; P = 0.006; P = 0.042). In contrast, a high density of intratumoral CD68+ cells and peritumoral CD163+ cells was significantly associated with poor OS durations (P = 0.026; P = 0.030). The multivariate analysis demonstrated that a high density of peritumoral CD163+ cells correlated with poor OS after adjusting for tumor stage, recurrence, and nodal lymphatic metastasis (P = 0.034). This study found different patterns of TAIC infiltration in LSCC. The density and location of TAICs infiltration correlated with the clinicopathological characteristics of LSCC. CONCLUSION: A combined analysis of the density of TAICs and their location may help predict patient survival and response to checkpoint inhibitors.

Does Socioeconomic Status Affect Stage at Presentation for Larynx Cancer in Canada's Universal Health Care System?

OBJECTIVE: Diagnosis of laryngeal cancer is dependent on awareness that persistent hoarseness needs to be investigated as well as access to an otolaryngologist. This study aimed to better classify and understand 3 factors that may lead to variability in stage at presentation of laryngeal cancer: (1) socioeconomic status (SES), (2) differences in access to health care by location of residence (rural vs urban or by province), and (3) access to an otolaryngologist (by otolaryngologists per capita). STUDY DESIGN: Registry-based multicenter cohort analysis. SETTING: This was a national study across Canada, a country with a single-payer, universal health care system. SUBJECTS: All persons 18 years or older who were diagnosed with laryngeal cancer from 2005 to 2013 inclusive were extracted from the Canadian Cancer Registry (CCR). METHODS: Ordered logistic regression was used to determine the effect of income, age, sex, province of residence, and rural vs urban residence on stage at presentation. RESULTS: A total of 1550 cases were included (1280 males and 265 females). The stage at presentation was earlier in the highest income quintile (quintile 5) compared to the lower income quintiles (quintiles 1-4) (odds ratio [OR], 0.68; P < .05). There was a statistically significant difference in stage at presentation based on rural or urban residence within the highest income quintile (OR, 1.73; P < .005). CONCLUSION: There is a relationship between SES and stage at presentation for laryngeal cancer even in the Canadian universal health care system.