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Simple Summary: A total laryngectomy and/or pharyngectomy is an important therapy modality for advanced primary and recurrent laryngeal and hypopharyngeal squamous cell carcinoma. The surgical margins are an important prognostic factor. Resection margins for head and neck cancer surgery are clear >5 mm, close 1–5 mm and positive <1 mm. However, the anatomy of the larynx and hypopharynx is complex and resections are constrained by the anatomical relationship with the surrounding structures. The aim of this study is to investigate if a margin >5 mm is feasible. Clear resection margins are not always feasible in some resection surfaces in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for the maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery. Background: Resection margins are an important prognostic factor for patients with head and neck cancer. In general, for head and neck surgery, a margin >5 mm is advised by the Royal College of Pathologists. However, this cannot always be achieved during laryngeal and hypopharyngeal surgery. The aim of this study is to identify the resection surfaces and measure the maximum feasible margins per subsite. The clinical relevance of these maximum feasible resection margins were analyzed in this descriptive anatomical study. Methods: head and neck surgeons and a pathologist from the Erasmus MC performed a total laryngectomy and laryngopharyngectomy on a head and neck specimen specifically available for research. Results: For a total laryngectomy, resection margins >5 mm were not feasible for the ventral and dorsal resection surface. For a total laryngopharyngectomy, resection margins >5 mm were not feasible for the ventral, dorsal and lateral resection surface. Conclusion: Clear resection margins, defined as a margin >5 mm, are not always feasible in laryngeal and hypopharyngeal surgery, due to the anatomy of the larynx and tumor location. However, striving for a maximum feasible margin is still the main goal. We propose a new guideline for maximum feasible but adequate resection margins in larynx and hypopharynx tumor surgery. [ABSTRACT FROM AUTHOR]

Simple Summary: Achieving margins of >5 mm is challenging in the larynx and hypopharynx because resections are constrained by their complex anatomy. The aim of this study was to retrospectively assess the clinical relevance of resection margins defined by the RCP in total laryngectomies (TLs) and total laryngopharyngectomies (TLPs). Similar survival rates for close and clear margins for primary and recurrent LSCC were found. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival, therefore a margin of 1–5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided. Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery. Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated. Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins (p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins. Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1–5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided. [ABSTRACT FROM AUTHOR]

Simple Summary: Anterior commissure involvement (ACI) is an important factor in the local control of early-stage glottic squamous cell carcinoma (EGSCC). We initiated a radiotherapeutic treatment regimen focusing on ACI, which has included hyperfractionated radiotherapy since 2008. One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. Hyperfractionated radiotherapy (74.4 Gy in 62 fractions) was used for EGSCC with ACI. The 10-year overall survival and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. In conclusion, hyperfractionated radiotherapy was effective for T1 disease with ACI but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation. Anterior commissure is involved in about 20% of early-stage glottic squamous cell carcinomas (EGSCCs). Treatment outcomes and prognostic factors for EGSCC with anterior commissure involvement (ACI) were evaluated by focusing on hyperfractionated radiotherapy (74.4 Gy in 62 fractions). One-hundred and fifty-three patients with T1–T2 EGSCC were included in this study. The median total doses for T1a, T1b, and T2 were 66, 74.4, and 74.4 Gy, respectively. Overall, 49 (32%) patients had T1a, 38 (25%) had T1b, and 66 (43%) had T2 disease. The median treatment duration was 46 days. The median follow-up duration was 5.1 years. The 10-year overall and cause-specific survival rates were 72% and 97%, respectively. The 10-year local control rates were 94% for T1a, 88% for T1b, and 81% for T2 disease. Local control rates in patients with ACI were slightly better than those in patients without ACI with T1a and T1b diseases; however, the difference was not significant. The 10-year laryngeal preservation rate was 96%. Six patients experienced grade 3 mucositis, and four patients had grade 3 dermatitis. Hyperfractionated radiotherapy was effective for T1 disease with ACI, but insufficient for T2 disease with ACI. Our treatment strategy resulted in excellent laryngeal preservation. [ABSTRACT FROM AUTHOR]

Objectives: Laryngeal squamous cell carcinoma (LSCC) is a common squamous cell carcinoma of the head and neck with no reliable diagnostic biomarkers. However, recent studies have shown that inflammation plays an essential role in tumor development, and several inflammation-based biomarkers have been shown to have prognostic value. This study aimed to investigate the auxiliary value of fibrinogen (FIB), fibrinogen degradation products (FDP), and lymphocyte/monocyte ratio (LMR) in LSCC diagnosis and prognosis. Methods: Clinical data from 218 patients recently diagnosed with LSCC and 207 diagnosed with benign laryngeal lesions (BLLs) were retrospectively reviewed. Potential diagnostic biomarkers were evaluated using univariate and multivariate analyses; receiver operating characteristic (ROC) curve analysis was used to identify cut-off values and diagnostic efficiency. Least absolute shrinkage and selection operator (LASSO) Logistic regression analysis was used to screen for independent risk factors to construct a diagnostic nomogram. The chi-squared test and Kaplan–Meier method were performed to investigate the correlation of clinicopathological characteristics and 3-year overall survival (OS) with FIB, FDP, and LMR in patients with LSCC. Results: FIB, FDP, and LMR levels were significantly different between the LSCC and BLL groups (P <.001), and all were independent risk factors for LSCC. The area under the ROC curve of the diagnostic nomogram was.894. Additionally, FIB, FDP, and LMR were correlated with some invasive clinicopathological features, and LMR ≥4.29 was associated with reduced OS (P =.038). Conclusion: FIB, FDP, and LMR demonstrated potential as biomarkers for the diagnosis and prognosis of LSCC; however, further studies are needed to confirm their efficacy. [ABSTRACT FROM AUTHOR]

This study compared the effects of megestrol acetate (MA) prophylactic (p-MA) versus reactive (r-MA) use for critical body-weight loss (>5% from baseline) during concurrent chemoradiotherapy (CCRT) in patients with advanced pharyngolaryngeal squamous cell carcinoma (PLSCC). Patients receiving CCRT alone in two phase-II trials were included for analyses. Both the p-MA and r-MA cohorts received the same treatment protocol at the same institution, and the critical body-weight loss, survival, and adverse event profiles were compared. The mean (SD) weight loss was 5.1% (4.7%) in the p-MA cohort (n = 54) vs. 8.1% (4.6%) in the r-MA cohort (n = 50) (p =.001). The percentage of subjects with body-weight loss >5% was 42.6% in the p-MA cohort vs. 68.0% in the r-MA cohort (p =.011). Tube feeding was needed in 22.2% of p-MA vs. 62.0% of r-MA patients (p <.001). Less neutropenia (26.0% vs. 70.0% [p <.001]) and a shorter duration of grade 3-4 mucositis (2.4 ± 1.4 vs. 3.6 ± 2.0 wk [p =.009]) were observed with p-MA treatment. Disease-specific survival, locoregional control, or distant metastasis-free survival did not differ. Less competing mortality from secondary primary cancer resulted in a better overall survival trend in the p-MA cohort. p-MA may reduce body-weight loss and improve adverse event profiles during CCRT for patients with PLSCC. [ABSTRACT FROM AUTHOR]

Background: Laryngocarcinoma (LC) is a common malignant tumor of the head and neck, accounting for 1% to 5% of human tumors. The primary objective of the present study was to evaluate the survival time of patients with LC at different sites. Methods: Information concerning patients with LC was extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 1975 and 2016. Results: In total, 16 255 patients with LC were selected from the SEER database. Among all patients, 80.2% were male; males also predominated in each tumor site subgroup. Most of the patients were aged between 60 and 69 years, had white ethnicity, were single, and had American Joint Committee on Cancer (AJCC) stage I cancer with T1, N0, and M0. The present study investigated the role of interventions in all LCs at different AJCC stages. Across the whole population, regardless of the intervention used, survival increased in patients at any cancer site. Conclusions: The study found that male sex, age ≥80 years, black ethnicity, single status, T4, N4, M1, and AJCC stage IV were associated with higher mortality rates at all sites of LC. Aggressive interventions, especially surgery and radiotherapy, may improve survival in patients with LC at different sites and with different AJCC stages. [ABSTRACT FROM AUTHOR]

Background: Treatment selection for squamous cell carcinoma patients aged over 84 years is controversial. This retrospective chart review examined and compared characteristics of laryngeal squamous cell carcinoma in very elderly (over 84 years) and younger patients (approximately 65 years). The secondary objective was to further evaluate the outcome of radiotherapy as a treatment modality in this patient population. Methods: Of all 23 very elderly patients with laryngeal squamous cell carcinoma treated with radiotherapy, with or without surgery, in the Davidoff Cancer Center, from 1992 to 2012, 19 had sufficient data for analysis, and comprised the study group. Results: Median age at diagnosis was 86 years. Disease stage at diagnosis was I, II, III and IVA in 53 per cent, 21 per cent, 21 per cent and 5 per cent, respectively. Median radiotherapy dose was 60 Gy given in 25 fractions. Three patients had recurrence. No patient discontinued treatment because of toxicity. Median overall survival was 3.6 years (range, 0–10 years). Conclusion: Very elderly laryngeal squamous cell carcinoma patients may derive a similar survival advantage as younger counterparts. Modern radiotherapy is effective and safe for treating laryngeal squamous cell carcinoma in this study population. Further, large-scale studies are needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral infection with high-risk human papillomaviruses is one of the known risk factors for oropharyngeal cancer. Human papillomavirus-related oropharyngeal cancer is a rising trend in many Western countries. Hong Kong is a vibrant Chinese cosmopolitan city in East Asia where data on the trend of change in human papillomavirus-related oropharyngeal cancer are not available. This study found that oropharyngeal cancer cases have increased persistently over the last three decades in Hong Kong, despite a notable decrease in other head and neck cancers such as the laryngeal cancer. By testing a series of cancer samples collected over the past several years, this study found that the proportion of oropharyngeal cancer infected with high-risk human papillomaviruses has increased substantially over the last decade. Strategies to prevent oral human papillomavirus infection and its associated diseases including oropharyngeal cancer are urgently needed. Research on the early detection of oropharyngeal cancer is a priority. The incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is rising in the West, but little is known in Asia. This study elucidated changes in the incidence and HPV-positive portion of OPSCC in Hong Kong. Data from population-based cancer registry were used to analyze the incidence of OPSCC in association with other head and neck cancers. Archived tumor tissues were tested for HPV. From 1986 to 2020, there was a marked decrease in the incidence of nasopharyngeal and laryngeal cancers, but a persistent increase in OPSCC from 36 cases in 1986 to 116 cases in 2020. The average positive rate for high-risk HPV was 36.1% (112/310) among OPSCC diagnosed in 2010–2020. The HPV-positive rate in recent years was significantly higher than earlier cases (tonsil SCC: 64.7% (55/85) in 2016–2020 vs. 40.4% (19/47) in 2010–2015, p = 0.007). Patients with HPV-positive tonsil cancers were significantly younger than those negative (mean [SD]: 58.9 [9.9] vs. 64.3 [13.3] years, p = 0.006), but no significant difference was observed between genders. A persistent increase in the incidence of oropharyngeal cancer over the last few decades was observed in Hong Kong, which can be explained by the remarkable increase in HPV-positive tonsil cancers. [ABSTRACT FROM AUTHOR]

Objective: To investigate epidemiological, clinical and oncological outcomes of patients with laryngeal verrucous carcinomas (LVC). Methods: Two independent authors investigated PubMed, Scopus and Cochrane Library for studies dedicated to epidemiological, clinical and oncological outcomes of patients with LVC. The following outcomes were investigated with PRISMA criteria: age; gender; tobacco/alcohol consumption; HPV infection; anatomical, pathological, therapeutic and survival outcomes. Studies were analyzed for bias through a validated clinical tool. Results: Of the 212 identified articles, 15 retrospective studies and one prospective uncontrolled study met our inclusion criteria. Three studies reported findings from national databases. The males/females ratio is 9/1. Mean age was 60.3 years, which was younger compared to other laryngeal malignancies. The alcohol, cigarette overuse and the HPV status of patients were lacking in most studies. Glottis and supraglottis were the most common anatomical locations, corresponding to 78.7% and 12.4% of cases, respectively. The main therapeutic approaches consisted of surgery, radiotherapy, surgery followed by radiotherapy. Treatments reported 5-year overall survival and disease-specific survival of 86.3 and 90.8, respectively. The 5- and 10-year local control rate were 83.6 and 72.6, respectively. The 10-year disease-specific survival was 80.2. Heterogeneity between studies was found for inclusion criteria, comorbidity data, and treatments. Conclusion: LVC is a rare laryngeal cancer associated with better survival and recurrence outcomes than laryngeal squamous cell carcinoma. The role of radiotherapy in the treatment regimen needs to be investigated in future prospective controlled studies. [ABSTRACT FROM AUTHOR]

Objectives: Despite the increasingly modern surgical techniques in the oncology field, the factors that influence postoperative prognosis in patients with hypopharyngeal and laryngeal carcinoma (HLC) remain unclear. The study aimed to evaluate the factors influencing the prognosis of HLC patients with pathological diagnosis of squamous cell carcinoma, and the findings are intended to direct follow-up management strategies. Methods: A retrospective cohort study was performed. The study population included 407 postoperative patients with HLC from 2011 to 2015. Univariate and multivariate analyses were used to examine the prognostic factors identified. Results: Based on univariate analysis results, smoking and alcohol history, tumor differentiation, preoperative radiotherapy, primary tumor sites, flap reconstruction, lymph node invasion (LNI), and preoperative albumin levels (PAL) significantly affects the prognosis of HLC patients (P <.05). Meanwhile, multivariate analysis revealed that smoking pack-year (OR = 1.002, 95% CI = 1.001 ∼ 1.003), primary tumor sites (OR = 6.241, 95% CI = 1.715 ∼ 18.433), LNI (OR = 2.869, 95% CI = 1.095 ∼ 8.743), and PAL (OR =.020, 95% CI =.004 ∼ 0.104) were associated with complications. Tumor differentiation (OR = 0.650, 95% CI =.383 ∼ 0.855), primary tumor sites (OR = 12.392, 95% CI = 3.290 ∼ 26.679), LNI (OR = 16.323, 95% CI = 2.726 ∼ 47.729), preoperative radiotherapy (OR = 9.300, 95% CI = 3.182 ∼ 27.181), and PAL (OR =.321, 95% CI =.141 ∼.732) were associated with overall survival rates. Conclusion: Smoking and alcohol history, tumor differentiation, LNI, primary tumor sites, flap reconstruction, PAL, and preoperative radiotherapy are crucial factors that influence the postoperative prognosis of patients with HLC. In addition, a monogram of five factors was established to predict the survival rates of HLC patients. [ABSTRACT FROM AUTHOR]

Introduction: Malignant transformations may result from gene dysregulation caused by genetic and epigenetic modifications. The use of miRNAs to treat cancer depends on the downregulation or upregulation of the miRNAs responsible for carcinogenesis (proliferation, angiogenesis, invasion, metastasis), providing the opportunity to suppress tumors. The purpose of this review is to list miRNAs identified so far as biomarkers in laryngeal squamous cell carcinoma (LSCC). This listing may help in predicting the evolution of miRNAs and developing anti-miRNAs and miRNA-mimics as anti-cancer therapies. Material and methods: Relevant publications from 2008 to 2022 were retrieved from the PubMed and Google Scholar databases, using the key words miRNA (PubMed -- 149,294 results; Google Scholar -- 205,000 results), laryngeal squamous cell carcinoma (PubMed -- 33,191 results; Google Scholar -- 17,900 results), laryngeal squamous cell carcinoma biomarkers (PubMed -- 6249 results; Google Scholar -- 18,000 results), laryngeal squamous cell carcinoma miRNA (PubMed -- 1338 results; Google Scholar -- 17,500 results). Eventually 51 papers were selected for review. Results: We identified 51 studies which have detected miRNA-based biomarkers for LSCC, and they are broadly reviewed here. Conclusions: The identified laryngeal squamous cell-specific miRNA biomarkers appear to be promising for the detection, predicted course, and treatment of LSCC. [ABSTRACT FROM AUTHOR]

Laryngeal cancer ranks as the second most prevalent upper airway malignancy, following Lung cancer. Although some progress has been made in managing laryngeal cancer, the 5-year survival rate is disappointing. The gradual increase in the incidence of second primary tumors (SPTs) plays a crucial role in determining survival outcomes during long-term follow-up, and the esophagus was the most common site with a worse prognosis. In clinical practice, the treatment of esophageal second primary tumors (ESPT) in patients with laryngeal squamous cell carcinoma (LSCC) has always been challenging. For patients with synchronous tumors, several treatment modalities, such as radiotherapy, chemotherapy and potentially curative surgery are necessary but are typically poorly tolerated. Secondary cancer therapy options for metachronous patients are always constrained by index cancer treatment indications. Therefore, understanding the clonal origin of the second primary tumor may be an important issue in the treatment of patients. LSCC cells demonstrate genetic instability because of two distinct aetiologies (human papillomavirus (HPV)-negative and HPV-positive) disease. Various etiologies exhibit distinct oncogenic mechanisms, which subsequently impact the tissue microenvironment. The condition of the tissue microenvironment plays a crucial role in determining the destiny and clonal makeup of mutant cells during the initial stages of tumorigenesis. This review focuses on the genetic advances of LSCC, the current research status of SPT, and the influence of key carcinogenesis of HPV-positive and HPV-negative LSCC on clonal evolution of ESPT cells. The objective is to gain a comprehensive understanding of the molecular basis underlying the clonal origins of SPT, thereby offering novel perspectives for future investigations in this field. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study compares the diagnostic efficacy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in detecting nodal disease with that of neck magnetic resonance imaging (MRI). It then measures the rate of change in therapy intent when relying on 18F-FDG PET/CT nodal staging results. In a group of 66 patients, our findings emphasize the importance of metabolic tumor volume and nodal size in distinguishing between benign and metastatic lymph nodes. These identified parameters present a promising avenue for reliably predicting nodal disease status, thereby offering robust imaging-based support for future research endeavors in this domain. This retrospective study examines the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and neck magnetic resonance imaging (MRI) in detecting nodal metastasis for patients with laryngeal squamous cell carcinoma (LSCC) and assesses the predictive values of metabolic and structural features derived from 18F-FDG PET/CT. By involving 66 patients from 2014 to 2021, the sensitivity and specificity of both modalities were calculated. 18F-FDG PET/CT outperforms neck MRI for nodal disease detection, with 89% sensitivity, 65% specificity, and 77% accuracy for nodal metastasis (p = 0.03). On the other hand, neck MRI had 66% sensitivity, 62% specificity, and 64% accuracy. Approximately 11% of patients witnessed a change in their therapy intent when relying on 18F-FDG PET/CT nodal staging results. Analyzing the cohort for PET-derived metabolic and morphological parameters, a total of 167 lymph nodes (LN) were visualized. Parameters such as the LN maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN size were computed. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Among the 167 identified cervical LNs, 111 were histopathologically confirmed as positive. ROC analysis revealed the highest area under the curve for LN MTV (0.89; p < 0.01), followed by LN size (0.87; p < 0.01). Both MTV and LN size independently predicted LN metastasis through multivariate analysis. In addition, LN MTV can reliably predict false-positive LNs in preoperative staging, offering a promising imaging-based approach for further exploration. [ABSTRACT FROM AUTHOR]

Simple Summary: Laryngeal squamous cell carcinoma is a prevalent cancer associated with poor prognosis in advanced stages. Despite advancements in diagnostic tools (e.g., narrow-band imaging), there have been minimal improvements in therapeutic approaches. The potential new frontier lies in the realm of biomarkers. This review aims to outline the current understanding of biomarkers in laryngeal cancer. Specifically, it concentrates on potential biomarkers, including heat shock proteins, metallothioneins, nuclear factor erythroid 2-related factor 2, micro ribonucleic acids, heme oxygenase, and cyclooxygenase-2. This review provides a survey of the existing literature on their role in laryngeal cancer. It also underscores the scarcity of the literature on this subject, highlighting the significant role of biomarkers in formulating more precise therapeutic strategies for individual patients. Laryngeal squamous cell carcinoma (LSCC) is the second most common cancer among head and neck cancers. Despite a lower incidence of laryngeal carcinoma, new diagnostic techniques, and more targeted therapies, the overall survival has not changed significantly in the last decades, leading to a negative prognosis in advanced stages. Recently, several studies have focused on the identification of biomarkers that may play a critical role in the pathogenesis of LSCC. Reviewing the literature on the main databases, this study aims to investigate the role of some biomarkers in LSCC that are correlated with oxidative stress and inflammation: heat shock proteins; metallothioneins; nuclear factor erythroid 2-related factor 2; heme oxygenase; cyclooxygenase-2; and micro ribonucleic acids. This review shows that biomarker expression depends on the type, grade of differentiation, stage, and site of carcinoma. In addition, the role of these biomarkers in LSCC is still little-known and little-studied. However, the study of biomarker expression and the detection of a possible correlation with patients' epidemiological, clinicopathological, and therapeutics data may lead to better awareness and knowledge of the tumor, to the identification of the best therapeutic strategy, and the most proper follow-up protocol tailored for each patient. In conclusion, the achievement of these goals may improve the prognosis of LSCC patients. [ABSTRACT FROM AUTHOR]

Background: Evidence on the risk of second primary cancer (SPC) following primary laryngeal squamous cell carcinoma (LSCC) is limited, especially in Europe. Methods: Patients diagnosed with primary LSCC from 1953-2018 were retrieved from the Finnish Cancer Registry. A total of 6241 LSCC patients were identified adding to 49,393 person-years (PY) of follow-up until the end of 2019. Only one patient emigrated and was lost to follow-up. Both standardized incidence ratios (SIR) and excess absolute risk (EAR) per 1000 person-years at risk (PYR) of second primary cancer (SPC) were calculated relative to the general population. Only non-laryngeal SPCs diagnosed six months after diagnosis of primary LSCC were included. Results: A SPC was diagnosed in 1244 LSCC patients (20% of all LSCC patients) over the 65-year period, predominantly in men (92%, n=1170). Out of all SPCs, 34% were diagnosed within 0.5 to 5 years and 66% after 5 years from primary LSCC. Among male patients, the overall SIR for SPC at any location was 1.61 (95% CI: 1.52-1.71), corresponding to 9.49 excess SPCs per 1000 PYR (95% CI: 8.19-11). The corresponding SIR for women was 1.47 (95% CI: 1.15-1.84), yielding 4.82 excess SPCs per 1000 PYR (95% CI: 2.36-9.84). The risk remained significant even after 20 years of follow-up (SIR for all 1.73, 95% CI: 1.49-2.01 and EAR 16.8 per 1000 PY, 11.88-23.75). The risk for SPC was also significantly elevated in all age groups, except <40. The highest SIRs were for SPCs arising in the mouth/pharynx (SIR for all 3.08, 95% CI: 2.36-3.95 and EAR 0.80 per 1000 PY, 0.55-1.15) and lungs (3.02, 2.75-3.30 and 5.90 per 1000, 5.13-6.78). Conclusion: Patients with LSCC as primary cancer have a 60% excess risk for an SPC, especially for tobacco-associated cancers, remaining significantly elevated even decades after treatment. NOVELTY & IMPACT Although prior research on the risk of second primary cancer (SPC) among laryngeal squamous cell carcinoma (LSCC) patients has been conducted in other regions, the European perspective remains notably underrepresented. Moreover, studies on the subject focusing especially on LSCC are, even globally, only a few. The present study, with over 6000 LSCC patients followed-up over six decades, consists of the largest reported cohort of LSCC patients in Europe, and with the longest follow-up. Patients with LSCC as a primary cancer have a 60% excess risk for an SPC, which remains significantly elevated even 20 years after the diagnosis of the first primary cancer, especially for those with a tobacco/alcohol-related cancer. Healthcare professionals should be aware of the SPC risk among LSCC survivors who should be counseled about this phenomenon. [ABSTRACT FROM AUTHOR]

Simple Summary: Treatment recommendations for head and neck cancer need to be disseminated worldwide becoming available through societies/authors scientific reports and websites with warning updates. This scoping review identifies and compares the worldwide clinical practice guidelines for treating oral, oropharynx, and larynx cancer. We verified the absence of guidelines in Latin American and Oceanian countries, as well as the inequalities between countries/continents, with a similar pattern of recommendations among low-income countries and in developed ones. Recommendations for surgery, radiotherapy, and chemotherapy may differ according to country/institution access and resources Head and neck cancer (HNC) treatments have been based on single or multimodal therapies with surgery, radiotherapy (RT), chemotherapy, and immunotherapy. However, treatment recommendations among countries may differ due to technological/human resources and usual local practices. This scoping review aims to identify, compare, and map the clinical practice guidelines (CPGs) for treating squamous cell carcinoma (SCC) of the oral cavity, oropharynx, and larynx worldwide. A search strategy on global CPGs for HNC was performed by using five electronic databases and grey literature. CPGs were selected for inclusion using EndNote-20 and Rayyan online software. No language or publication date restrictions were applied. The results were analyzed descriptively considering the most updated CPG version. In total, 25 CPGs covering the head and neck region (10), the larynx (7), the oral cavity (5), and the oropharynx (3), were found in 13 geographical regions, and 19 were developed by medical societies from 1996 to 2023. Surgery and RT remain the main modalities for early-stage HNC, with surgery preferred in low-resource countries, and RT in selected cases, especially in the larynx/oropharynx aiming to achieve a cure with organ preservation. Human papillomavirus infection for oropharyngeal SCC is not tested in some Asian countries and there is still no consensus to treat p16-positive cases differently from p16-negative. Recommendations for larynx preservation vary according to facilities in each country, however, individualized choice is emphasized. Inequality across countries/continents is evident, with a similar pattern of recommendations among developed as well as developing ones. No CPGs were found in Latin America as well as Oceania countries, where the incidence of HNC is high and limitations of access to treatment may be encountered. [ABSTRACT FROM AUTHOR]

Simple Summary: Vaccination against human papillomavirus (HPV) helps prevent cancer caused by this virus. Determining which viral genotypes should be included is key for developing successful vaccination strategies. Low-risk genotypes, especially HPV6 and HPV11, are associated with benign warts. However, some studies also report their presence in cancers. We reviewed the scientific literature to estimate the proportion of cancers that bear single or dual HPV6/11 infections. HPV6 and HPV11 have been reported in up to 5.5% of penile and 87.5% of laryngeal cancers; however, they have not been reported in vulvar, vaginal or oral cancers. Next, we compared the HPV6/11 genomes with HPV16, the most common high-risk HPV genotype, and observed that the similarities mainly involved the E7 gene, suggesting a limited ability to interfere with the differentiation of the host cells. These findings support the use of HPV vaccines that cover HPV6/11 not only for preventing genital warts but also for preventing specific types of cancers. High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0–5.5% for penile and 0–87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the E7 gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) represents one of the principal tumors of the head and neck. Human papillomavirus (HPV) and Epstein–Barr virus (EBV) are considered risk factors for the development and the clinical prognosis of LSCC. High levels of p16INK4a are suggested as a surrogate marker of HPV or EBV infection in some head and neck tumors but in LSCC is still controversial. Furthermore, pRb expression may be considered an additional biomarker but it has not been clearly defined. This work aimed to compare the expression of pRb and p16INK4a as possible biomarkers in tumor tissues with and without infection by EBV or different genotypes of HPV from patients with LSCC. Methods: Tumor samples from 103 patients with LSCC were previously investigated for the presence and genotypes of HPV using the INNO-LiPA line probe assay and for the infection of EBV by qPCR. p16 INK4a and pRb expression was assessed by immunohistochemistry. Results: Of the 103 tumor samples, expression of p16INK4a was positive in 55 (53.4%) and of this, 32 (56.1%) were positive for HPV whereas 11 (39.3%) were EBV positive but both without a significantly difference (p > 0.05). pRb expression was positive in 78 (75.7%) and a higher frequency of this expression was observed in HPV negative samples (87.0%) (p = 0.021) and in high-risk HPV negative samples (85.2%) (p = 0.010). No difference was observed when comparing pRb expression and EBV infection status (p > 0.05). Conclusion: Our results support the suggestion that p16INK4a is not a reliable surrogate marker for identifying HPV or EBV infection in LSCC. On the other hand, most of our samples had pRb expression, which was more frequent in tumors without HPV, suggesting that pRb could indicate HPV negativity. However, more studies with a larger number of cases are required, including controls without LSCC and evaluating other molecular markers to determine the real role of p16INK4a and pRb in LSCC. [ABSTRACT FROM AUTHOR]

Objective: Early detection of hypopharyngeal squamous cell carcinoma (SCC) is important for both an improved prognosis and less-invasive treatment. We retrospectively analyzed the detection rates of early hypopharyngeal SCCs according to the evaluation methods and the clinical management of early hypopharyngeal SCCs. Methods: Sixty-eight patients with early hypopharyngeal SCC who were diagnosed were reviewed. Results: The number of early hypopharyngeal cancer patients with asymptomatic or synchronous or metachronous esophageal cancer examined by upper gastrointestinal endoscopy with narrow-band imaging (NBI) was significantly higher than those examined by laryngopharyngeal endoscopy with NBI. The 3-year disease-specific survival rates according to T classification were as follows: Tis, 100%; T1, 100%; T2, 79.8%; and overall, 91.2%, respectively. Conclusions: Early-stage hypopharyngeal SCC can be cured by minimally invasive transoral surgery or radiotherapy. Observation of the pharynx using NBI in patients with a history of head and neck cancer, esophageal cancer, gastric cancer, or pharyngeal discomfort is very important, and routinely examining the pharynx with NBI, even in patients undergoing endoscopy for screening purposes, is recommended. [ABSTRACT FROM AUTHOR]

Objective: For low-grade intraepithelial neoplasia cases, pharyngolaryngeal lesions equal to or less than 5 mm in size do not generally progress to invasive carcinoma. However, micro-superficial lesions equal to or less than 5 mm that showed rapid growth have been recently encountered. This study aimed to identify the characteristics of preferential progression of lesions equal to or less than 5 mm in size. Method: Gross findings, endoscopic findings and pathological results of 55 lesions measuring equal to or less than 5 mm in diameter were retrospectively reviewed to identify factors that distinguish squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions. Results: The overall sensitivity, specificity, accuracy, and positive and negative predictive value of background colouration and intrapapillary capillary loop pattern in differentiation of squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions were all 100 per cent. Conclusion: Diagnosis based on background colouration and the intrapapillary capillary loop pattern on narrow-band imaging facilitates the pathological examination of lesions measuring equal to or less than 5 mm. [ABSTRACT FROM AUTHOR]

Simple Summary: Laryngeal cancer is a relatively common neoplasm of head and neck, whose management hinges on a combination of treatments such as surgery, radiotherapy and chemotherapy. Tumor recurrences may present important differences from the primary tumor that largely depend on previous treatments. the immune system plays a crucial role in the natural course of the disease, owing the capability to influence its behavior through a complex interaction of mechanisms. For this reason, the use of immunotherapy in addition to standard therapies is increasingly gaining importance nowadays and the selection of patients who can benefit the most from this treatment can help optimizing its success. However, conventional treatments can induce relevant changes in the host immune response, thus affecting tumor progression and patient outcome. This fact should be taken into account when planning immune-based treatments like immune checkpoint inhibitors. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal cancer, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Recurrent laryngeal carcinoma presents differences from the primary tumor that largely depend on the treatment. In this article, we review the histologic and molecular treatment-induced changes that may affect the diagnosis of recurrent laryngeal carcinoma, the assessment of predictive markers, and the response to treatment with immune checkpoint inhibitors. Radiotherapy induces profound modifications that are strictly related to necrosis of different tissue components, fibrosis, and damage of the tumor vessels. Postradiotherapy recurrent/persistent laryngeal squamous cell carcinoma typically presents a discohesive growth pattern within a fibrotic background associated with significant changes of the tumor immune microenvironment, with both important immunosuppressive and immunostimulatory effects. Overall, the increase of immunoregulatory cells and immune checkpoints such as CTLA-4, TIM-3, PD-1, and PD-L1 induced by radiotherapy and chemotherapy strongly supports the use of immune checkpoint inhibitors in recurrent/persistent laryngeal carcinoma. Future studies aiming to identify predictive factors of the response to immune checkpoint inhibitors should consider such treatment-induced modifications. [ABSTRACT FROM AUTHOR]

Background: For recurrent laryngeal cancer, the feasibility of salvage transoral laser microsurgery (TLM) remains controversial. This study compared the efficacy of TLM and open partial laryngectomy (OPL) for treatment of early local recurrence of glottic squamous cell cancer (GSCC) and confirm the effectiveness of salvage TLM as a treatment option. Methods: This retrospective study involved 55 patients with early local recurrent GSCC treated with TLM, and the oncologic outcomes, functional outcomes, hospitalization time and complications were compared with a group of 40 recurrent GSCC patients matched for clinical variables of TLM group, treated by OPL by the same team of surgeons. Results: The 5-year overall survival and disease-specific survival rates were 65.8% and 91.5%, respectively, for 55 patients with rTis–rT2 stage treated by TLM and 77.1% and 94.7%, respectively, for 40 patients with rTis–rT2 stage treated by OPL (OPL group). In the TLM and OPL groups, the local control rates after 5 years were 77.5% and 79.3%, respectively, and the laryngeal preservation rates were 94.4% and 83.6%, respectively (p > 0.05). Compared with the OPL group, the complication rate (1.82%) and hospitalization duration (5.42 ± 2.26 days) were significantly lower in the TLM group (p < 0.05). Compared with the OPL group, postsurgical health-related quality of life and quality of voice were significantly better in the TLM group (p < 0.001). Conclusion: Salvage TLM can be used as an effective treatment option for suitable patients after a full, comprehensive, and careful assessment of the characteristics of early locally recurrent glottic carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of human papillomavirus (HPV) in the survival of patients with head and neck squamous cell carcinoma (HNSCC) is an important topic. The recognition of additional markers could play a significant role in survival prognosis. Our study aimed to assess the roles of different molecular and immunohistochemical factors in the survival of patients with HNSCC. We analyzed 106 HNSCC samples and confirmed the roles of HPV DNA and p16, p53, and HPV16 E6 and E7 proteins in different subgroups of HNSCC. In addition to p16, the immunohistochemical overexpression of HPV16 E6 protein should be used for patient survival prognosis. The role of HPV in the survival prognosis of patients with head and neck squamous cell carcinoma, especially patients with laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC), is still somewhat ambiguous. The present study aimed to explore the significance of tumor suppressor proteins and HPV16 E6 and E7 oncoproteins in the assessment of survival in patients with oropharyngeal squamous cell carcinoma (OPSCC), LSCC, and HPSCC associated with high-risk (HR-) and low-risk (LR-) HPV infections. By utilizing molecular and immunohistochemical investigations of HNSCC samples and patient data, univariate and multivariate survival analyses were conducted. The presence of HPV DNA (LR- and HR-HPV) was associated with a better 5-year OS and DSS for OPSCC and LSCC. The IHC overexpression of HPV16 E6 protein and p16 protein was associated with better survival in the univariate (for OPSCC) and multivariate (OPSCC and HPSCC) survival analyses. The overexpression of p53 was associated with better survival in OPSCC. HPV infection plays a significant role in the tumorigenesis of HNSCC, and the immunohistochemical assessment of HPV16 E6 protein expression should be interpreted as a useful prognostic marker for OPSCC and HPSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: We are going to highlight new prognostic and predictive factors, CD44, PDL1, and ATG7, in surgical samples from patients with laryngeal squamous cell carcinoma (LSCC). Immunohistochemical analysis with primary antibodies anti-CD44, PD-L1 and ATG7 was performed using the tissue microarray (TMA) technique. Considering follow-up data, the 5-year disease-free survival (DFS) was 85.71% and 36% for CD44-negative and -positive tumors. The 5-year DFS was 60% and 33.33% for negative and positive PDL1 tumors, respectively. At the follow-up, 5-year DFS was 58.06% and 37.50% for negative and positive ATG7 tumors. We focus on the new prognostic and predictive factors CD44, PDL1, and ATG7 in our study of surgical samples of patients with laryngeal squamous cell carcinoma (LSCC) using tissue microarray (TMA). Thirty-nine previously untreated patients affected by laryngeal carcinoma who then underwent surgical treatment were considered in this retrospective study. All surgical specimens were sampled, embedded in paraffin blocks, and stained with hematoxylin and eosin. A representative sample of the tumor was chosen and transferred into a new block of paraffin, the recipient block, to perform immunohistochemical analysis with the primary antibodies anti-CD44, PD-L1, and ATG7. At follow-up, 5-year disease-free survival (DFS) for negative and positive tumors was determined as 85.71% and 36% for CD44, 60% and 33.33% for PDL1, and 58.06% and 37.50% for ATG7, respectively. Multivariate analysis revealed that CD44 expression is an independent predictive factor of low-grade tumors (p = 0.008), lymph node metastasis at the time of diagnosis, and AGT7 negativity. Thus, CD44 expression is a potential marker for more aggressive forms of laryngeal cancer. [ABSTRACT FROM AUTHOR]

Background: There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. Method: This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). Results: Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. Conclusion: Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: This retrospective study is the first attempt to investigate the tumor–stroma ratio in a series of laryngeal basaloid squamous cell carcinomas (SCCs), comparing them with a group of stage-matched conventional SCCs, in both preoperative and surgical specimens. This study's aim was to ascertain the biological aggressiveness of laryngeal basaloid SCCs and to investigate any possible role of stromal-related features in such a clinical behavior. The tumor–stroma ratio, evaluated in laryngeal biopsies and in the entire excised tumor, displayed a prognostic effect in terms of reduced disease-free survival in conventional SCC cases but not in basaloid ones. Basaloid squamous cell carcinoma (BSCC) is a subtype of squamous cell carcinoma (SCC) associated with a poor prognosis. Tumor–stroma ratio (TSR) has been introduced as a prognostic feature in many solid tumors. TSR was investigated in a series of laryngeal BSCCs and compared with a group of stage-matched conventional SCCs (cSCCs), in both preoperative and surgical specimens, with the intent of ascertaining the more aggressive behavior of BSCC and verifying the presence of stromal-related causes. A series of 14 consecutive laryngeal BSCCs and a control group of 28 stage-matched conventional cSCCs were analyzed. A higher nodal metastasis presence was found in BSCCs (57.1% vs. 28.6%). The recurrence rate was 33.5% and 63.6% in the cSCC and BSCC groups; disease-free survival (DFS) was higher, though not significantly, in patients with cSCC. TSR, large cell nests, and tumor budding showed a moderate to very good agreement, and stroma type a good to very good agreement between biopsies and surgical specimens in the cSCC group. In the BSCC group, agreement was poor to very good for TSR and stroma type, and good to very good for large cell nests and tumor budding. Age was the only feature significant in predicting recurrence in the BSCC group (p = 0.0235). In cSCC, TSR low/stroma rich cases, when evaluated on biopsies or surgical specimens, were associated with lower DFS (p = 0.0036; p = 0.0041, respectively). Laryngeal BSCCs showed a lower DFS than cSCCs, even if statistical significance was not reached. TSR, evaluated in laryngeal biopsies and excised tumors, was prognostic in terms of DFS in cSCC but not in BSCC cases. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to investigate key long noncoding RNAs (lncRNAs) involved in competitive endogenous RNA (ceRNA) network associated with laryngeal squamous cell carcinoma (LSCC). Materials and Methods: Three mRNA datasets, two miRNA datasets, and one lncRNA dataset of LSCC were downloaded from GEO database. Following the identification of differentially expressed mRNAs (DEmRNAs), (microRNAs) miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) in LSCC compared with adjacent tissues, functional enrichment of DEmRNAs was performed. Then, construction of the ceRNA (DElncRNA‐DEmiRNA‐DEmRNA) regulatory network and functional analyses of all DEmRNAs in ceRNA regulatory network were conducted. Quantitative real‐time polymerase chain reactions (qRT‐PCR) were used to detect the expression levels of selected DEmRNAs, DEmiRNAs, and DElncRNAs. Results: A total of 3449 DEmRNAs, 40 DEmiRNAs, and 100 DElncRNAs were identified in LSCC. The ceRNA networks, which contained 132 DElncRNA‐DEmiRNA pairs and 287 DEmiRNA‐DEmRNA pairs, involving 44 lncRNAs, 3 miRNAs, and 271 mRNAs, were obtained. DEmRNAs in ceRNA regulatory networks were significantly enriched in pathways in cancer, prostate cancer, and aldosterone‐regulated sodium reabsorption. Except for HCG22 and hsa‐miR‐1246, expressions of the others in the qRT‐PCR results played the same pattern with that in our integrated analysis, generally. Conclusions: We concluded that HCG22/EGOT‐hsa‐miR‐1275‐FAM107A and HCG22/EGOT‐hsa‐miR‐1246‐Glycerol‐3‐phosphate dehydrogenase 1 like interaction pairs may play a central role in LSCC. [ABSTRACT FROM AUTHOR]

Aim: Long non‐coding RNAs were widely reported to regulate laryngeal squamous cell carcinoma (LSCC), a prevalent tumor in the head and neck. We aimed to investigate the role of solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1‐AS1) in LSCC. Materials & methods: CCK‐8 and colony formation assays were conducted to examine the viability and proliferation of LSCC cells. The apoptosis of LSCC cells was evaluated using flow cytometry and TUNEL assays. The distribution of SLCO4A1‐AS1 in LSCC cells was detected by subcellular fractionation assay. The interaction between molecules was confirmed using luciferase reporter assay. Results: SLCO4A1‐AS1 was overexpressed in LSCC tissues and cells. Furthermore, silenced SLCO4A1‐AS1 repressed the proliferation and facilitated apoptosis of LSCC cells. Mechanistical investigation revealed that SLCO4A1‐AS1 was a competing endogenous RNA (ceRNA) to upregulate SETD7 by binding with miR‐7855‐p. Additionally, SLCO4A1‐AS1 positively regulated the Wnt/β‐catenin signaling pathway by upregulating SETD7. Rescue experiments demonstrated that SLCO4A1‐AS1 promoted LSCC proliferation and inhibited LSCC apoptosis by upregulation of SETD7 and activation of the Wnt/β‐catenin pathway. Conclusion: SLCO4A1‐AS1 promotes proliferation and inhibits apoptosis of LSCC cells by upregulation of SETD7 in a miR‐7855‐5p dependent way to activate the Wnt/β‐catenin pathway. [ABSTRACT FROM AUTHOR]

Simple Summary: The central compartment of the neck is not cleared during a comprehensive neck dissection, which usually encompasses neck levels I to V. When involved by clinically evident lymph node metastases, central neck compartment dissection is mandatory; on the other hand, precise indications regarding the elective surgical management of occult lymph node metastases at this level are still a matter of debate. Laryngeal and hypopharyngeal squamous cell carcinomas can spread to regional lymph nodes located in the central neck compartment. This anatomic region contains the laryngeal nerves, the thyroid, and parathyroid glands, and its boundaries are represented by major vessels. This paper will focus on relevant clinical aspects that must be considered in order to formulate a judicious balance between the probability of dealing with occult disease and the possibility of being confronted with unnecessary iatrogenic risks. Metastatic lymph node involvement represents the most relevant prognostic factor in head and neck squamous cell carcinomas (HNSCCs), invariably affecting overall survival, disease-specific survival, and relapse-free survival. Among HNSCCs, laryngeal and hypopharyngeal cancers are known to be at highest risk to metastasize to the central neck compartment (CNC). However, prevalence and prognostic implications related to the CNC involvement are not well defined yet, and controversies still exist regarding the occult metastasis rate. Guidelines for the management of CNC in laryngeal and hypopharyngeal cancers are vague, resulting in highly variable selection criteria for the central neck dissection among different surgeons and institutions. With this review, the authors intend to reappraise the existing data related to the involvement of CNC in laryngeal and hypopharyngeal malignancies, in the attempt to define the principles of management while highlighting the debated aspects that are lacking in evidence and consensus. Furthermore, as definition and boundaries of the CNC have changed over the years, an up-to-date anatomical–surgical description of the CNC is provided. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) is the most common histological type of laryngeal cancer. Several variants of SCC have been reported. However, how these variants differ from conventional SCC and how they should be treated remain to be elucidated. To compare the prognosis of early-stage glottic cancer among SCC variants We obtained data from 12471 cases using the Surveillance, Epidemiology, and End Results database. Disease-specific survival (DSS) and overall survival (OS) rates were estimated using the Kaplan–Meier method. A Cox proportional hazard model was used to estimate hazard ratios (HRs) according to the variants. HRs for DSS and OS compared with well-differentiated SCC were 3.83 and 3.48 for adenosquamous, 1.42 and 1.42 for basaloid, 1.14 and 1.17 for papillary, 0.85 and 0.94 for spindle, and 0.81 and 1.00 for verrucous SCC. The difference in DSS among the treatment modalities was significant in conventional and papillary SCC (p <.001 and p =.032, respectively). The prognosis of SCC variants, except for adenosquamous SCC, is comparable to that of conventional SCC. [ABSTRACT FROM AUTHOR]

Objective: Carotid sinus syndrome (CSS) is a rare yet serious presentation of head and neck malignancy. To our knowledge, syncope and seizure-like episodes as a manifestation of carotid sinus syndrome secondary to laryngeal cancer has not been reported to date. We report a case of laryngeal cancer causing convulsive syncope masquerading as seizures due to CSS. Methods: Case report. The patient's medical record was reviewed for demographic and clinical information. Results: A 62-year-old male presented with multiple episodes of syncope and hoarseness of voice. On nasoendoscopic examination, left vocal cord palsy and left aryepiglottic fold tumor were visualized. Computerized tomography (CT) neck showed a large 2.4 × 3.6 cm left supraglottic tumor with local invasion and extensive cervical lymphadenopathy compressing the carotid sinus. CT guided biopsy of the tumor revealed invasive squamous cell carcinoma. While undergoing evaluation, the patient developed seizure-like episodes. Inpatient telemetry monitoring revealed significant bradycardia and hypotension during these episodes. A permanent pacemaker was inserted which resulted in resolution of the syncopal and seizure-like episodes. Conclusion: In patients with unexplained syncope or seizure-like episodes and a background of head and neck cancer, clinicians should consider the diagnosis of CSS. CSS is a poor prognostic factor due to the associated higher stage of disease. [ABSTRACT FROM AUTHOR]

The article presents the case of a 79-year-old man who was diagnosed with T2N2bM0 squamous cell carcinoma (SCC) to discuss a unique application of linear endobronchial ultrasound (EBUS) bronchoscope for supraglottic biopsy of a locally recurring laryngeal SCC. Also cited is the recommendation by a multidisciplinary tumor board for him to undergo total laryngectomy with neck dissection rather than palliative chemotherapy.

Objective. Laryngeal squamous cell carcinoma (LSCC) is a common malignant tumor. Laminin 5γ2 chain (LAMC2) was reported to be associated with tumorigenesis. This study explored the role of LAMC2 on LSCC progression by regulating the integrinβ1/FAK/Src/AKT pathway. Methods. The level of LAMC2 in 46 LSCC patients was detected by qRT-PCR and western blot. Then the relationship between LAMC2 expression and LSCC malignancy as well as prognosis was analyzed, and the effect of LAMC2 expression on LSCC patient survival was also analyzed using the Kaplan–Meier survival curves. Afterwards, the LSCC cells were transfected with LAMC2 overexpression and knockdown vectors, the effect of LAMC2 on LSCC cell viability, proliferation ability, cell cycle, cell migration, and invasion were detected by CCK-8, colony formation, flow cytometry, wound healing, and Transwell assays. The expression of EMT-related biomarkers and integrin β1/FAK/Src/AKT signaling-related proteins was detected by western blot. Moreover, the effect of LAMC2 on LSCC tumor growth was evaluated by in vivo xenograft experiments and western blot. Results. LAMC2 was expressed at high level in LSCC tissues and associated with poor prognosis. LAMC2 overexpression increased TU177 cell viability, proliferation ability, promoted cell cycle, cell migration, and invasion capacity. The expression of N-cadherin, vimentin, and integrinβ1/FAK/Src/AKT related proteins was increased, while the expression of E-cadherin protein was decreased. When the LAMC2 knockdown in AMC-HN-8 cells had opposite effects. Furthermore, shLAMC2 decreased tumor volume and the expression of LAMC2, Ki-67 and integrinβ1, but increased the expression of E-cadherin in LSCC tumor-bearing mice. Conclusion. The findings suggested that LAMC2 was overexpressed in LSCC and correlated with poor prognosis. LAMC2 knockdown inhibited LSCC progression by regulating the integrinβ1/FAK/Src/AKT signaling pathway. Therefore, LAMC2 could be a target for LSCC therapy. [ABSTRACT FROM AUTHOR]

Background. Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignant tumor of the head and neck with a dismal prognosis. Keratin17 (KRT17) has been proven to serve as an oncogene in various cancers, but it has never been explored in LSCC. We proposed to assess the impact and possible mechanisms of KRT17 in the development of LSCC. Methods. Quantitative reverse transcription-PCR (qRT-PCR) was utilized to examine the mRNA levels. The Kaplan–Meier method was used to calculate the relationship between KRT17 expression and survival curves in LSCC patients. Cell counting kit-8 (CCK-8), colony formation, and flow cytometry assays were utilized to estimate LSCC cell proliferation. The migration and invasion abilities of LSCC cells were ascertained by wound-healing and transwell assays. Immunohistochemical and western blot assays were utilized to appraise protein levels. The xenograft tumor model was used to determine the effect of KRT17 on tumor growth. Results. In the present study, KRT17 was extremely high in LSCC tissues and cells and correlated with a poor prognosis. Inhibition of KRT17 weakens cell proliferative, migratory, and invasive abilities in LSCC and contributes to cell cycle arrest. Besides, we approved that knockdown of KRT17 extraordinarily restrained the xenograft tumor growth in vivo. We preliminarily investigated the role of KRT17 on the AKT/mTOR and Wnt/β-catenin signaling axes and found that these signaling pathways were largely blocked by KRT17 deletion. Conclusion. Collectively, we uncovered that exhaustion of KRT17 suppresses LSCC progression through coordinating AKT/mTOR and Wnt/β-catenin signaling axes, illustrating KRT17 as a promising biomarker for making strides in LSCC treatment. [ABSTRACT FROM AUTHOR]

Objective: Current evidence suggests there is no difference between endoscopic laser surgery and radiotherapy with regards to oncological outcomes of early laryngeal cancer. Patient management may therefore be directed towards voice and quality of life outcomes. This systematic review compares functional outcomes with respect to voice character, swallowing outcomes and quality of life for endoscopic laser surgery versus radiotherapy for T1 and T2 stage laryngeal carcinoma. Method: Search terminology was designed by both authors and used in Cochrane, PubMed and Web of Science databases. Studies of adult patients treated for primary T1 and T2 laryngeal squamous cell carcinoma utilising one objective (validated) measure of quality of life, swallowing or voice were included. Results: Initial searches identified 1767 studies. After inclusion and exclusion criteria were applied, 42 studies were identified for full-text review. Conclusion: This review concluded that neither treatment is clearly advantageous. Future research should be composed of further prospective studies that use a standardised assessment regime to allow valid comparison. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Red blood cell distribution width (RDW), a reported biomarker for morbidity and mortality in chronic disease and following certain surgeries, has not been well-studied in head and neck cancer patients. The aim of the study was to examine the association of RDW with postoperative complications and survival among patients who underwent primary or salvage laryngectomy. Methods: We analyzed a retrospective case series study of patients diagnosed with squamous cell carcinoma of the larynx treated with total laryngectomy. Survival outcomes were examined using Kaplan-Meier analysis. Results: One hundred seventy-seven patients were included in the final analysis. The most common tumor subsite was the supraglottis (60%). On bivariate analysis, patients with RDW ≥14.5 had higher prevalence of non-surgical, systemic complications, including deep venous thrombosis, pneumonia, cardiovascular events, and difficulty weaning from mechanical ventilation. However, there was no significant difference in laryngectomy-specific post-operative complications, including pharyngocutaneous fistula, wound infection, stoma complications, and chyle leak. RDW was not found to be associated with survival outcomes following laryngectomy. Conclusions: Among laryngectomy patients, RDW ≥14.5 is associated with higher prevalence of systemic morbidity, but not with specific local surgical complications or decreased survival. [ABSTRACT FROM AUTHOR]

Background. The possible role and detailed mechanisms of Tumor-associated macrophages (TAMs) in laryngeal squamous cell carcinoma (LSCC) have not been revealed. Methods. The expressions of typical markers were evaluated by qRT-PCR. In macrophages cocultured with TU212 cells, CD163, and CD206 protein expressions were detected by western blot analysis; IL-10 and IL-12 expressions were detected by ELISA assay. Exosomes isolated from TU212 cells were characterized by TEM analysis. As for the TU212 cells cocultured with macrophages processed with HOK or TU212 cells derived exosomes, their viability, migration, and invasion were assessed by CCK-8 assay, wounding healing, and Transwell assays, respectively. Results. In this study, macrophages processed with exosomes from human TU212 cells notably advanced LSCC cell viability, migration, and invasion. miR-1246 inhibitor suppressed the M2 polarization of macrophages. Macrophages transfected with miR-1246 inhibitor suppressed LSCC cell viability, migration, and invasion. Conclusion. In summary, our data implied that the exosomal, miR-1246 of LSCC, induced polarization of M2 type macrophages and promoted the progression of LSCC. This trial is registered with 2020-13. [ABSTRACT FROM AUTHOR]

Carotid artery involvement in head and neck cancer is challenging for surgeons and oncologists, particularly in recurrence or residual disease following multiple treatments. However, carotid artery resection and reconstruction can be safely performed in a carefully selected patient with local and regional control benefits despite the potential morbidity and high-risk complications. We presented a case of primary laryngeal cancer treated with chemoradiotherapy, modified radical neck dissection type I for residual neck node disease, and further chemotherapy. Although the primary laryngeal cancer showed a complete response, the residual neck tumor was still unresolved and even involved the carotid artery. Therefore, carotid resection with a combined saphenous vein graft and free flap reconstruction was the treatment of choice for this patient. It is effective and safe, and the risk of morbidity has been accepted. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) incidence has been escalating in the last two decades, particularly in Western Europe and North America. Human papillomavirus (HPV) has been identified as the main culprit for this rise with significant implications for the treatment and outcomes of these patients. The purpose of this retrospective study was to investigate HPV's impact on HNSCC patient outcomes in the Irish population, which has never been performed before. HPV positivity of HNSCC appears to be associated with improved survival in patients and highlights the importance of surgery, perhaps with less severe chemo-radiation therapy, in HPV-related HNSCC treatment. Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV's involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV's impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention. [ABSTRACT FROM AUTHOR]

We present a new oral intake route in a hypopharyngeal cancer patient with severe complications. A 64-year-old man was diagnosed as having T2N0M0 squamous cell carcinoma of the posterior wall of the hypopharynx. He had previously undergone radiotherapy for laryngeal cancer and tricuspid valve replacement surgery, and also had atrial flutter and renal dysfunction. We performed surgery with curative intent. The hypopharynx was primarily closed after tumor resection. Laryngotracheal separation and tracheoesophageal diversion with end-to-end anastomosis of the trachea to the esophagus was performed. After surgery, complete oral feeding was achieved using the new pathway created. The larynx, contradictory to its typical role, can be used as a pathway to the esophagus using our revolutionary technique. [ABSTRACT FROM AUTHOR]

Objectives: Selective radiotherapy and concomitant intra-arterial cisplatin infusion (m-RADPLAT) with a lower cisplatin dosage have been performed for organ and function preservation in patients with locally advanced squamous cell carcinoma of the larynx (SCC-L), and results showing a lower rate of adverse events have been reported. This study evaluated the treatment outcomes of patients with T3N0 glottic SCC-L with or without vocal fold fixation (VFF) who were treated with m-RADPLAT. Methods: We retrospectively reviewed the data of 33 patients with T3N0 SCC-L who received m-RADPLAT. Results: The vocal fold in patients with VFF 3 months after completing m-RADPLAT resumed normal movement in 15 patients (83%) and persisted fixation in 3 (17%). The 3-year local control, laryngeal cancer-specific survival, and overall survival rates of patients with or without VFF were 88.9% and 86.7%, 94.1% and 93.3%, and 88.9% and 86.7%, respectively. Additionally, the 3-year freedom from laryngectomy, laryngectomy-free survival, and laryngo-esophageal dysfunction-free survival rates of patients with or without VFF were 94.4% and 86.7%, 88.9% and 73.3%, and 83.3% and 73.3%, respectively. Grade 3 or higher toxicities were observed in all patients: leukopenia in 4 patients (12%), neutropenia in 5 (15%), anemia in 2 (6%), thrombocytopenia in 3 (9%), and mucositis in 2 (6%). Conclusions: This study demonstrated that m-RADPLAT yielded VFF improvement and a favorable survival while maintaining laryngeal function not only in patients with T3N0 glottic SCC-L without VFF but also in patients with VFF. [ABSTRACT FROM AUTHOR]

Most current larynx cancer therapies are generally aimed at the global mass of tumor, targeting the non-tumorigenic cells, and unfortunately sparing the tumorigenic cancer stem cells (CSCs) that are responsible for sustained growth, metastasis, and chemo- and radioresistance. Phytochemicals and herbs have recently been introduced as therapeutic sources for eliminating CSCs. Therefore, we assessed the anti-tumor effects of two herbal ingredients, the green tea extract "Epigallocatechin-3-gallate (EGCG)" and Honokiol (HNK), on parental cells or CD44high CSCs of the human laryngeal squamous cell carcinoma cell line HEp-2. Results revealed that EGCG had a preeminent apoptotic potential on HEp-2 laryngeal CSCs. HNK conferred higher cytotoxic impacts on parental cells mostly by necrosis induction, especially with higher doses, but apoptosis induction with lower doses was also observed. The Notch signaling pathway genes were more potently suppressed by EGCG than HNK. However, HNK surpassed EGCG in downregulating the β-catenin and the Sonic Hedgehog signaling pathways genes. On a genetic basis, both agents engaged the BCL-2 family-regulated and caspase-dependent intrinsic apoptotic pathway, but EGCG and HNK triggered apoptosis via p53-independent and p53-dependent pathways, respectively. Taken together, EGCG and HNK eradicated HEp-2 human larynx cancer cells through targeting multiple self-renewal pathways and activating diverse cell death modalities. [ABSTRACT FROM AUTHOR]

Chemoradiation therapy is standard practice for hypopharyngeal and laryngeal cancer, but its impact on skin health can cause complications if salvage surgery is required. To develop simple objective indices for the early detection of complications following head-and-neck salvage surgery. Preoperatively and on postoperative days 1, 3, 5 and 7, we measured skin hardness (N), interstitial liquid content (П) and intracellular liquid content (W) as biophysical properties in patients who underwent post-CRT salvage therapy and those who underwent total organ resection without CRT as controls. We then analyzed these data in relation to occurrence of complications. In 11 patients undergoing salvage surgery and 23 controls, complications tended to be higher (p =.54) in the salvage group. N values were significantly higher in the salvage and complication groups on days 5 and 7, П values were higher in the complication group on day 7, and W values were lower in the complication group on day 3 and in the salvage group preoperatively and on days 1 and 5. N, П and W are useful measurements for the early identification of patients likely to develop complications. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) of the vocal cord in stages I or II can be treated with radiotherapy (RT) or transoral CO2 laser microsurgery (TLM), with good oncological results. To study the survival of patients with SCC of the vocal cord in early stages, treated with RT or TLM, in a tertiary hospital. Disease-free survival (DFS), specific survival (SS), and overall survival (OS) were studied in patients diagnosed with stage I and II SCC of the vocal cord, for a span of 10 years of follow-up, based on sociodemographic characteristics of the patient and the primary treatment (TLM or RT). Both treatments achieved good survival rates. However, long-term SS was greater in patients treated with TLM compared to those treated with RT (91.7% vs. 50%, respectively, p =.001). In addition, patients treated with TLM presented a higher OS in the short term than those treated with RT (99.0% vs. 89.1%, respectively. p =.004). Primary treatment with TLM obtained better results than RT in the survival of patients with SCC of the vocal cord in the early stages. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is one of the highly aggressive malignancy types of head and neck squamous cell carcinomas; genes involved in the development of LSCC still need exploration.Methods: We downloaded expression profiles of 96 (85 in advanced stage and 11 in early stage) LSCC patients from TCGA-HNSC. Function enrichment and protein-protein interactions of genes in significant modules were conducted. Univariate and multivariate Cox regression analyses were performed to explore potential prognostic biomarkers for LSCC. The expression levels of genes at different stages were compared and visualized via boxplots. Immune infiltration was examined by the CIBERSORTx web-based tool and depicted with ggplot2. Gene set enrichment analysis (GSEA) was utilized to analyze functional enrichment terms and pathways. Immunohistochemical staining (IHC) was used to verify the expression of genes in the LSCC samples.Results: We identified 25 modules, including 3 modules significantly related to tumor stages of LSCC via weighted gene co-expression network analysis (WGCNA). UIMC1, NPM1, and DCTN4 in the module 'cyan', TARS in the module 'darkorange', and COPB2 and RYK in the module 'lightyellow' showed statistically significant relation to overall survival. The expression of COPB2, DCTN4, RYK, TARS, and UIMC1 indicated association with the change of fraction of immune cells in LSCC patients; two genes, COPB2 and RYK, indicated different expression in various tumor stages of LSCC. Finally, COPB2 and RYK showed high-expression in tumor tissues of advanced LSCC patients.Conclusions: Our study provided a potential perceptive in analyzing progression of LSCC cells and exploring prognostic genes. [ABSTRACT FROM AUTHOR]

Tumor size, inflammation, and nutritional status may be correlated with the immune response to cancer. Our hypothesis is that there is an interrelationship among tumor size, inflammatory response, and body mass index (BMI), and that these variables could alter T-lymphocyte infiltration in patients with laryngeal squamous cell carcinoma (LSCC). A retrospective cohort of 91 surgical LSCC patients treated at a Brazilian National Cancer Reference Center was followed for 5 years. We collected data regarding BMI, clinical factors, patients' lifestyle, C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). Data were obtained in the medical records within a maximum interval of 7 days before surgery. The stromal and intratumoral CD4+ and CD8+ T-cell infiltrations were obtained by immunohistochemistry. Our results demonstrated a significant correlation among tumor size and BMI, NLR, PLR, and LMR. Similarly, PLR and LMR were significantly correlated with BMI. Tumor size and inflammatory parameters were not associated with changes in T-cell infiltrations. However, patients with low BMIs had a significantly lower density of intratumoral CD4+ T lymphocytes infiltrated when compared with normal/high BMI patients (odds ratio, 0.14; 95% confidence interval, 0.03-0.58; P =.007). CD8+ T-lymphocyte infiltration did not change in low-BMI patients. In conclusion, we observed a correlation among tumor size, inflammation, and BMI. Tumor size/inflammation axis may be responsible for the change in BMI and, therefore, may have influenced the reduction of intratumoral CD4+ T-lymphocyte infiltration in LSCC patients. [Display omitted] The literature describes a possible intrinsic relationship between tumor size, inflammation and nutritional status. These factors may influence the tumor host's immune response. We analyzed CD4+ and CD8+ T-lymphocyte infiltration in tumor tissues samples obtained from surgical LSCC patients and also investigate the interrelationship of these variables. Among all the variables tested, only BMI showed and independent and significant association with intratumoral CD4+ T-lymphocytes The literature describes a possible intrinsic relationship between tumor size, inflammation and nutritional status. These factors may influence the tumor host's immune response. We analyzed CD4+ and CD8+ T-lymphocyte infiltration in tumor tissues samples obtained from surgical LSCC patients and also investigate the interrelationship of these variables. Among all the variables tested, only BMI showed and independent and significant association with intratumoral CD4+ T-lymphocytes infiltration. [ABSTRACT FROM AUTHOR]

Objective: Laryngeal squamous cell carcinoma has a high mortality rate, and approximately 60% of patients are in advanced stage at the time of diagnosis. Thus, determining the prognostic parameters of this cancer and markers related to these parameters are very important. There are studies showing that heat shock-related 70-kDa protein 2, which is used as a biomarker, may be associated with prognostic parameter in some cancers. However, no study has investigated the prognostic role of heat shock-related 70-kDa protein 2 in laryngeal squamous cell carcinoma in the literature. Thus, in our study, the aim was to examine the relationship between heat shock-related 70-kDa protein 2 expression and clinicopathological prognostic parameters in laryngeal squamous cell carcinoma. Materials and Methods: Our study included 104 patients diagnosed with laryngeal squamous cell carcinoma between January 2005 and January 2016. The correlation between heat shock-related 70-kDa protein 2 expression and prognostic parameters was investigated by using the immunohistochemical method with heat shock-related 70-kDa protein 2 antibody. Results: In all the cases, heat shock-related 70-kDa protein 2 positivity was determined in tumoral areas (100%). The overexpression rate of heat shock-related 70-kDa protein 2 in adjacent non-cancerous tissues with dysplasia was 48/104 (42%) (P < .0001). A significant relationship was found between heat shock-related 70-kDa protein 2 expression and important prognostic parameters such as macroscopic tumor size, lymphovascular invasion, primary tumor, lymph node metastasis, distant organ metastasis, tumor, node, metastasis (TNM) stage stage, recurrence, and survival rates (P < .05). Conclusion: Our study supports the presence of an association between high heat shock-related 70-kDa protein 2 expression levels and prognostic parameters in laryngeal squamous cell carcinoma. We consider that heat shock-related 70-kDa protein 2 can be used as a prognostic marker in laryngeal squamous cell carcinoma. In addition, it may be important in early diagnosis due to its increased expression even under laryngeal squamous cell carcinoma precursor conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: Laryngeal Squamous Cell Carcinoma (LSCC) is a squamous cancer with 2.4% new diagnoses each year, accounting for 25% of head and neck cancers, and has a high mortality rate. A deeper understanding of key mechanisms and knowledge of the putative target molecules of theranostic relevance are required. The receptor for neurotrophins p75NTR has been shown to be highly expressed in cancer stem cells (CSCs) of squamous epithelia, in LSCC as well as in other cancers. However, whether its cleavage product p75ICD expression, known to finely regulate the survival/death balance in neurons, is also a master regulator in cancer and LSCC in particular has not been directly addressed so far. To resolve this question, we performed a preliminary study using a limited number of LSCC specimens and studied p75ICD presence and expression pattern in LSCC specimens, showing that p75ICD may be a promising target in LSCC, requiring further investigation. We investigated the p75 Neurotrophin Receptor (p75NTR) expression and cleavage product p75NTR Intracellular Domain (p75ICD) as potential oncogenic and metastatic markers in human Laryngeal Squamous Cell Carcinoma (LSCC). p75NTR is highly expressed in Cancer Stem Cells (CSCs) of the laryngeal epithelia and it has been proposed as a marker for stemness, cell migration, and chemo-resistance in different squamous carcinomas. To investigate the clinical significance of p75NTR cleavage products in solid tumors, full-length and cleaved p75NTR expression was analyzed in laryngeal primary tumors from different-stage LSCC patients, diagnosed at the Policlinico Umberto I Hospital. Molecular and histological techniques were used to detect the expressions of p75NTR and p75ICD, and ATP Binding Cassette Subfamily G Member 2 (ABCG2), a CSC marker. We found regulated p75NTR cleavage during squamous epithelial tumor progression and tissue invasion. Our preliminary investigation suggests p75ICD expression and localization as possible features of tumorigenesis and metastaticity. Its co-localization with ABCG2 in squamous cells in the parenchyma invaded by the tumor formation allows us to hypothesize p75NTR and p75ICD roles in tumor invasion and CSC spreading in LSCC patients. These data might represent a starting point for a comprehensive analysis of p75NTR cleavage and of its clinical relevance as a potential molecular LSCC signature, possibly helping diagnosis, and improving prognosis and personalized therapy. [ABSTRACT FROM AUTHOR]