Search

Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy in Asia. Infection by human papilloma virus (HPV) has been recognized as an etiological risk for HNSCC, especially oropharyngeal region. While the association between HPV and HNSCC has been well evaluated in Western countries, only a few investigated the HPV-associated HNSCC in Southeast Asia. This study evaluated the prevalence, the characteristics, and the impact of HPV on the treatment outcomes in Thai HNSCC patients., Methods: Non-nasopharyngeal HNSCC patients treated at Ramathibodi Hospital during 2007-2013 were identified through the cancer registry database. Baseline patient, treatment data and survivals were retrospectively reviewed. The formalin-fixed paraffin-embedded (FFPE) tissue sections were retrieved for p16 analysis. The HPV status was determined by p16 immunohistochemistry. The survival outcomes were analyzed in cases which p16 status was confirmed., Results: Total of 200 FFPE tissues of HNSCC patients was evaluated for p16 expression. Positive p16 status was observed in 24 cases (12%); majority of p16-positive were men (20:4 cases). The oropharynx (37.9%) was the most common site found in p16-positive while oral cavity (3.2%) was the least common site. Interestingly, 66.7% of p16-positive were former/current smokers, and 70.8% of this subgroup was categorized as clinical AJCC stage III-IV. The p16-positive HNSCC was significantly superior in 5-year overall survival [5-yrs OS 63% vs. 40%, p=0.03], 5-year disease-free survival [5-yrs DFS 61% vs. 36%, p=0.03] and in 5-year locoregional relapse-free survival [5-yrs LRFS 93% vs. 68%, p=0.018] when compared with p16-negative., Conclusions: In comparison to the results from the Western countries, the prevalence of HPV-related HNSCC in Thai patients was less, and differences in some characteristics were observed. Nevertheless, improvement in OS, DFS and LRFS were observed in p16-positive patients. Our analyses suggested that p16 status is also a strong prognostic marker for HNSCC patients in Thailand.

Background: No predictive biomarker of immune checkpoint inhibitors in head and neck squamous cell carcinoma (HNSCC) has been well established. The impact of programmed death-ligand 1 (PD-L1) expression, CD8+ tumor-infiltrating lymphocytes (TILs), and p16 status in HNSCC is unclear and may vary according to ethnicity., Methods: HNSCC patients treated between 2007 and 2013 were reviewed. Archival tissues were retrieved for PD-L1, CD8+ TILs, and p16 analyses. PD-L1 expression was evaluated by using the validated SP142 assay on the VENTANA platform. CD8+ TILs were defined by using semiquantitative scoring., Results: A total of 203 patients were analyzed. PD-L1 expression was observed in 80% of patients and was significantly associated with older age (P < 0.001). A high CD8+ TIL score (≥ 6) was significantly associated with never-smoking (P = 0.020), oral cavity cancer (P < 0.001), and stage M0 at presentation (P = 0.025). The p16 status was positive in 12% of patients. Patients with a high TIL score had a significantly longer OS (P = 0.032). Patients with PD-L1 expression of 1-49% and ≥ 50% were associated with a significantly shorter OS compared with those with PD-L1 < 1% (P = 0.027 and P = 0.011, respectively). Multivariate analysis showed that PD-L1 ≥ 50% was significantly associated with a poor OS. (HR 2.98 [95% CI 1.2-7.39]; P = 0.019.) CONCLUSIONS: A high prevalence of PD-L1 expression was observed in HNSCC using the validated SP142 assay. PD-L1 expression was associated with older age, while highly PD-L1 expression (≥ 50%) was an independent prognostic factor for poor OS in anti-PD1/PD-L1 untreated HNSCC patients.

Objective: To study the efficacy of peritubal infiltration in postoperative pain following percutaneous nephrolithotomy in general PCNL patients and PCNL patients with supracostal renal access., Patients and Methods: A total of 105 PCNL patients were randomized into two groups, 53 patients receiving peritubal analgesic infiltration (study group) and 52 patients as the control group. Of these patients, supracostal access was performed in 22 patients of study group and 23 patients of control group. The study group received peritubal injection with 10mL of bupivacain. Postoperative pain as the primary outcome was assessed by using visual analogue scale at 1, 4, 12, 24 and 48 hours postoperatively. The secondary outcomes were the total postoperative morphine usage in 24 hours and time of the first analgesic demand., Results: The average VAS pain at 1 and 4 hours after the operation in the study group were significant lower in the control group (P≤ 0.001 and 0.026). Doses of morphine usage for controlling postoperative pain and the first analgesic demand were significantly lower and longer in study group. Among patients submitted to supracostal access, the average VAS pain at 1 hour after operation in the study group was lower (P=0.018). Doses of morphine usage for controlling postoperative pain also was lower in the study group (P=0.012)., Conclusion: The peritubal local anesthetic infiltration is effective in alleviating immediate postoperative pain after percutaneous nephrolithotomy even with supracostal access.

Objective: To investigate the effect of local prilocaine infiltration on postoperative pain in patients undergoing percutaneous nephrolithotomy (PCNL). Materials and Methods: The case-control study enrolled 137 patients who underwent PCNL at Çukurova University Balcalı Hospital from April 2022 to December 2022. These patients were categorized into two distinct groups: The case and control groups. While peritubal 2% 10 cc prilocaine local anesthetic infiltration was applied to the cases, local anesthetic was not applied to the control group. Pain was evaluated using an analog scale after surgery. Results: In the study, which included 137 patients, local anesthesia was administered to 46 patients. Receiving local anesthesia was associated with the pain score (p<0.001). Pain scores were lower at the beginning and at the 4th minute in patients receiving local anesthesia (p<0.001 and p=0.004, respectively). Conclusion: Infiltration of peritubal prilocaine has been shown to notably diminish pain following PCNL. Our hypothesis suggests that local anesthetic infiltration into the nephrostomy tract could present a superior alternative for postoperative pain control. Nevertheless, extensive and prolonged follow-up studies are imperative for advancing research in this domain. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC), particularly oropharyngeal squamous cell carcinoma (OPSCC), is an increasingly prevalent pathology worldwide, especially in developed countries. For diagnosing HPV in HNSCC, the combination of p16 immunohistochemistry (IHC) and polymerase chain reaction (PCR) offers high sensitivity and specificity, with p16 IHC being a reliable initial screen and PCR confirming HPV presence. Advanced techniques like next-generation sequencing (NGS) and RNA-based assays provide detailed insights but are primarily used in research settings. Regardless of HPV status, standard oncological treatments currently include surgery, radiation, and/or chemotherapy. This conventional approach does not account for the typically better prognosis of HPV-positive HNSCC patients, leading to increased chemo/radiation-induced secondary morbidities and reduced quality of life. Therefore, it is crucial to identify and detect HPV positivity and other molecular characteristics of HNSCC to personalize treatment strategies. This comprehensive review aims to summarize current knowledge on various HPV detection techniques and evaluate their advantages and disadvantages, with a focus on developing methodologies to identify new biomarkers in HPV-positive HNSCC. The review discusses direct and indirect HPV examination in tumor tissue, DNA- and RNA-based detection techniques, protein-based markers, liquid biopsy potentials, immune-related markers, epigenetic markers, novel biomarkers, and emerging technologies, providing an overall insight into the current state of knowledge. [ABSTRACT FROM AUTHOR]

Purpose: Head and Neck squamous cell carcinoma (HNSCC) is the seventh most common cancer in the world. The prognosis of patients with HNSCC remains unsatisfactory, with a 5-years survival rate of only approximately 50%. In western Uganda, the 1-year survival rate is only 1%. Programmed cell death ligand 1 (PD-L1) and p16 have been shown to predict the progression of HNSCC lesions, prognosticate survival, reveal new therapeutic targets, and predict response to therapeutic agents. HNSCC patients with positive PD-L1 expression have been reported to benefit from immunotherapy; however, data on PD-L1 expression in HNSCC in Uganda and Africa are still lacking. This study aimed to determine the expression of PD-L1 in HNSCC and its association with p16 expression in Southwestern Uganda. Patients and Methods: We retrospectively studied 165 formalin-fixed paraffin-embedded specimens from the head and neck region with a previous histological diagnosis of squamous cell carcinoma (SCC). The specimens were retrieved from June 2012 to June 2022. Hematoxylin and eosin (H&E) staining was performed to confirm the diagnosis, followed by immunohistochemical (IHC) staining for PD-L1 and p16 using the laboratory developed technique. Results: Of the 165 specimens included in the study, 80% of source patients were male and the majority (51.5%) were older than 60 years. The oral cavity was the predominant site (51.52%). PD-L1 was expressed in 32.1% (95% C.l: 25.4– 39.68) of the specimens, whereas p16 was expressed in 16.36% (95% C.l: 11.4– 22.9). There was a statistically significant association between PD-L1 and p16 expression. Conclusion: The prevalence of PD-L1 expression in HNSCC in southwestern Uganda is low, implying that a number of patients with HNSCC can benefit from immunotherapy. PD-L1 expression may predict p16 expression and therefore HPV infection in HNSCC. [ABSTRACT FROM AUTHOR]

Head and Neck Squamous Cell Carcinoma (HNSCC) is one of the most common malignancies worldwide with most of the patients presenting in advanced stage. The associated high mortality and poor prognosis of the tumour has rendered the search for better therapeutic options than the traditional modalities of surgery, radiotherapy and chemotherapy. Immunotherapy targeting Programmed Cell Death Protein 1 / Programmed Cell Death Ligand 1 (PD-1/PD-L1) has been approved in recurrent/ metastatic HNSCC cases. PD-L1 expressing HNSCCs are likely to respond to immunotherapy. PD-L1 expression has been studied in peripheral blood utilising Circulating Tumour Cells (CTC) and soluble exosomes. Despite these non invasive techniques, PD-L1 expression has been most frequently assessed by immunohistochemistry (IHC) application on the Formalin Fixed Paraffin Embedded (FFPE) tissue of the tumour. Currently, many antibody clones and various IHC platforms are available for PD-L1, but only 22c3 has been approved by the Food and Drug Administration (FDA). Although, the availability of multiple options has made PD-L1 assessment possible and affordable at many centres worldwide, but various procedural, pre-analytical, and analytic issues have to be considered prior to the interpretation of immunoexpression of PD-L1. In this review, the authors aim to highlight the problem areas, and to understand the implications of PD-L1 expression in HNSCC. The authors propose recommendations for the optimal assessment of PD-L1 expression in HNSCC on IHC. [ABSTRACT FROM AUTHOR]

Head and neck cancers (HNC) are a biologically diverse set of cancers that are responsible for over 660,000 new diagnoses each year. Current therapies for HNC require a comprehensive, multimodal approach encompassing resection, radiation therapy, and systemic therapy. With an increased understanding of the mechanisms behind HNC, there has been growing interest in more accurate prognostic indicators of disease, effective post-treatment surveillance, and individualized treatments. This chapter will highlight the commonly used and studied biomarkers in head and neck squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment (TME) of HNSCC is heterogeneous and complex, and it plays a crucial role in achieving effective cancer therapy. To develop effective cancer therapies, it is important to understand the crosstalk between cancer inflammation and immunity, as well as oncogenes and tumor suppressor genes. In this study, we aimed to gain a more comprehensive understanding of the transcriptomes of the TME in HPV-associated and HPV-non-associated TSCC by studying the gene expression profiles of 168 genes linked to various cellular mediators and factors involved in inflammation, immune crosstalk, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. We found that the TME of HPV-associated and HPV-non-associated TSCC exhibited a remarkable heterogeneity of gene expression associated with cellular mediators and factors involved in inflammation, immune crosstalk, transcription factors, immune signaling pathways, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Head and neck squamous cell carcinomas (HNSCCs) are a common type of cancer, ranking as the sixth most prevalent cancer worldwide and having a high morbidity and mortality rate. Among oropharyngeal squamous cell carcinoma (OPSCC) cancers, tonsillar squamous cell carcinoma (TSCC) is the most prevalent and has a particularly aggressive clinical course with poor disease outcomes. The tumor microenvironment (TME) of HNSCC is complex and heterogeneous, playing a crucial role in effective cancer therapy. Understanding the interaction between cancer inflammation, immunity, oncogenes, and tumor suppressor genes is essential for developing effective cancer treatments. This study aimed to gain a comprehensive understanding of the transcriptomes of the TME in TSCC, both associated with human papillomavirus (HPV) and not associated with HPV. The gene expression profiles of 168 genes linked to various cellular mediators and factors involved in inflammation, immunity crosstalk, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis were analyzed. We identified 40 differentially expressed genes related to the communication between tumor cells and the cellular mediators of inflammation and immunity crosstalk. In HPV-positive TSCC patients, 33 genes were over-expressed with a fold change greater than 1.5, and 26 of these genes were unique to this group. In contrast, HPV-negative TSCC patients had 11 up-regulated genes. The results further showed that 48 gene transcripts related to oncogenesis, tumor suppression, angiogenesis, and apoptosis were up-regulated in both HPV-positive and HPV-negative TSCC patients. Among the HPV-positive TSCC patients, 37 genes were over-expressed, while the HPV-negative TSCC patients had 11 up-regulated genes. The tumor microenvironment (TME) of HPV-associated and HPV-non-associated TSCC exhibited distinct characteristics, including the dysregulation of various genes involved in cellular mediators, inflammation, immunity crosstalk, transcription factors, immune signaling pathways, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Additionally, we detected six Hr-HPV genotypes in 81% of the TSCC patients, with HPV-16 and HPV-35 being the most common types, followed by HPV-45 and HPV-18. HPV-39 and 31 were also identified. The presence of Hr-HPV genotypes in TSCC patients varied from single to multiple infections. In conclusion, we observed distinct heterogeneity in the transcriptome of the microenvironment in HPV-associated and non-associated TSCC. Further in vitro and in vivo studies are needed to investigate the functional implications of the identified over-expressed genes. Also, deeper molecular pathways and immunological studies on the TME are required to determine the potential of targeting genes for cancer therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: There is often a mismatch between the chronological and biological age of head and neck cancer patients. Treatment is based on chronological age, while biological age seems to be a better predictor for treatment toleration. The aim of this study was to assess whether tumor characteristics are associated with chronological and biological age, and the relation with survival. We observed that, in biologically old patients, a lower infiltration of CD163+ macrophages as well as CD4+ and CD8+ lymphocytes was found in the tumor microenvironment. Chronological older patients showed significantly lower PD-L1 combined positive scores. It can be concluded from these data that biological age might have a stronger influence on tumor microenvironment than chronological age. This emphasizes the need for studies investigating the response to specific treatment regimens (e.g., immunotherapy) according to biological age. There is often a mismatch between the chronological and biological age of head and neck squamous cell carcinoma (HNSCC) patients. Treatment is based on chronological age, while biological age seems to be a better prognosticator for treatment toleration. This study investigated whether tumor characteristics are associated with chronological and biological age. The relation with survival was also assessed. Prospectively collected data from 164 newly diagnosed HNSCC patients enrolled in the OncoLifeS database were analyzed. Biological age was assessed by a multidomain geriatric assessment. Several immunological markers were tested by immunohistochemistry on tissue microarray sections from the tumor. Disease-free survival (DFS), adjusted for chronological- and biological age, was assessed by univariable and bivariable analyses. In biologically old patients, a lower infiltration of CD163+ macrophages (p = 0.036) as well as CD4+ (p = 0.019) and CD8+ (p = 0.026) lymphocytes was found in the tumor microenvironment. Chronological older patients showed significantly lower PD-L1 combined positive scores (p = 0.030). Advanced tumor stage and perineural growth were related to a worse DFS. None of the immunological markers showed a significant association with DFS. Biological age might have a stronger influence on tumor microenvironment than chronological age. These findings should initiate clinical studies investigating the response to specific treatment regimens (e.g., immunotherapy) according to the biological age. [ABSTRACT FROM AUTHOR]

Anti‐programmed cell death 1 (anti‐PD‐1) therapy shows definite but modest activity in patients with advanced/metastatic head and neck squamous cell carcinoma (HNSCC). Preliminary evidence suggests that SN‐38, an activated form of irinotecan that increases expression of the transcription factor FoxO3a, can suppress programmed cell death ligand‐1 (PD‐L1) expression in breast and ovarian tumor models. We analyzed the SN‐38‐mediated activation of natural killer cells in vitro and explored the efficacy of SN‐38 in combination with anti‐PD‐1 for treatment in vivo. In vitro, SN‐38 enhanced the expression of FoxO3a and reduced the expression of c‐Myc and PD‐L1 dose‐dependently in tumor cells. Low‐dose SN‐38 increased interferon‐γ secretion by NK cells and promoted NK cell‐mediated cytotoxicity in tumor cells. In vivo studies revealed that at non‐cytotoxic drug concentrations, SN‐38 significantly enhanced anti‐PD‐1 activity in suppressing murine tumor growth. We found increased NK cell and CD8+ T‐cell infiltration in post‐treatment tumors. RNA‐seq analysis indicated that SN‐38 increased the enrichment of immune cells and biological function genes related to the immune responses. SN‐38 is a potentially beneficial adjunct to checkpoint inhibitor therapy in HNSCC. Further studies exploring its mechanism of action and possible applications are necessary. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background & Objective: Head and Neck Squamous Cell Carcinoma (HNSCC) is a highly frequent malignancy worldwide and is also the leading cause of death. The prognosis for individuals with HNSCC remains dismal, with a five-year survival rate of less than 50%. The novel anti-PD-L1 immunotherapy is found to be promising, and immunohistochemistry (IHC) has been established as a reliable method for patient stratification. We intend to evaluate the prognostic significance of the expression of programmed death ligand-1 (PD-L1) in HNSCC and determine its association with clinicopathological variables. Methods: A total of 50 cases of biopsy-confirmed HNSCC were studied in a tertiary hospital between Dec 2020 and June 2022. The specimens were tested for PD-L1 IHC expression with antibody clone CAL-10 (Biocare) and scored by Combined Positive Score (CPS). The association between PD-L1 expression and clinicopathological variables was evaluated. Results: PD-L1 was positive in 92% of the cases, and a significant association (P= 0.024) was seen between PD-L1 expression and tumor-infiltrating lymphocytes (TILs). PD-L1 did not show any significant association with patient demographics, tumor site, grade, or stage. Conclusion: In the present study, evaluation of the immunohistochemical expression of PD-L1 on the tumor cells and TILs in HNSCC revealed a high prevalence of PD-L1 expression. PD-L1 IHC studies for patient selection for immunotherapy would be a promising technique. Frequent PD-L1 expression in tumors with significant TILs may be useful in identifying patients who may benefit from anti-PD-1/PD-L1 therapy. [ABSTRACT FROM AUTHOR]

To evaluate the effect of quadratus lumborum block (QLB) for postoperative analgesia after percutaneous nephrolithotomy (PCNL), we searched Pubmed, Embase, Cochrane library, the Chinese Biomedical Literature Database, and randomized controlled trials (RCTs) assessing analgesic efficacy of QLB for PCNL are included in this meta-analysis. The related trials met the inclusion criteria were analyzed using RevMan 5.4 software, the weighted mean difference (WMD), with their corresponding 95% CI, was calculated to compare continuous variables. Nine RCTs are included in the meta-analysis showed that QLB group had significantly lower opioids consumption (WMD − 29.59 95% CI − 43.64 to − 15.55; P < 0.00001), lessen visual analog scale (VAS) after surgery 2 h (WMD − 1.35, 95% CI − 1.93 to − 0.76; P < 0.00001), 6 h (WMD − 1.47, 95% CI − 2.04 to − 0.91; P < 0.00001) 12 h (WMD − 1.75, 95% CI − 3.17 to − 0.32; P = 0.02) and 24 h (WMD − 1.4, 95% CI − 1.86 to − 0.94; P < 0.00001), shorter hospital stay(WMD − 0.7, 95% CI -1.26 to − 0.14, P < 0.00001) and reduce intestinal exhaust recovery time (WMD − 7.41, 95% CI − 9.36 to − 5.46, P < 0.00001) than in the control group. QLB offers some potential advantages in terms of opioids consumption, VAS, hospital stay and intestinal exhaust recovery time. However, good quality and large studies with long-term follow-up are warranted for further research. [ABSTRACT FROM AUTHOR]

Background: Worldwide prevalence of Oropharyngeal Squamous Cell Carcinoma (OPSCC) has increased, affecting mostly young males. OPSCC associated with Human Papillomavirus (HPV) infection exhibits particular characteristics in terms of response to treatment, hence HPV has been proposed as a prognostic factor. The impact of HPV positivity and associated biomarkers on OPSCC in the Mexican population has not been addressed. Therefore, the analysis of OPSCC prognostic markers in the Mexican population is necessary. Methods: Retrolective study in Mexican OPSCC patients, where HPV prevalence, p16 and EGFR levels were assessed using INNO-LiPA and immunohistochemistry. Results: We found an HPV prevalence of 57.6% in OPSCC cases treated at a reference center in Mexico. HPV and p16 positivity, as well as EGFR, associate with better outcomes in OPSCC patients, and they also promote reduced death risk. Notably, HPV presence and p16 positivity showed a significant association with disease-free survival (DFS), with a HR of 0.15 (p = 0.006) and a HR of 0.17 (p = 0.012), respectively, indicating a possible role as predictive biomarkers in Mexican OPSCC patients. Conclusions: Our results reflect the clinical utility of p16 analysis to improve overall survival (OS) and to predict recurrence in oropharyngeal cancer. These results position p16 and HPV as predictive biomarkers for OPSCC. [ABSTRACT FROM AUTHOR]

Head and neck cancer has high heterogeneity with poor prognosis, and emerging researches have been focusing on the prognostic markers of head and neck cancer. PD-L1 expression is an important basis for strategies of immunosuppressive treatment, but whether it has prognostic value is still controversial. Although meta-analysis on PD-L1 expression versus head and neck cancer prognosis has been performed, the conclusions are controversial. Since PD-L1 and PD-L2 are two receptors for PD-1, here we summarize and analyze the different prognostic values of PD-1, PD-L1, and PD-L2 in head and neck cancer in the context of different cell types, tissue localization and protein forms. We propose that for head and neck cancer, the risk warning value of PD-1/PD-L1 expression in precancerous lesions is worthy of attention, and the prognostic value of PD-L1 expression at different subcellular levels as well as the judgment convenience of prognostic value of PD-1, PD-L1, PD-L2 should be fully considered. The PD-L1 evaluation systems established based on immune checkpoint inhibitors (ICIs) are not fully suitable for the evaluation of PD-L1 prognosis in head and neck cancer. It is necessary to establish a new PD-L1 evaluation systembased on the prognosis for further explorations. The prognostic value of PD-L1, PD-L2 expression in head and neck cancer may be different for early-stage and late-stage samples, and further stratification is required. [ABSTRACT FROM AUTHOR]

The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathological development. Dysregulation of N6‐methyladenosine (m6A) modification has begun to emerge as a significant contributor to cancer development and progression. However, the biological effects and molecular mechanisms of m6A modification in arecoline‐promoted OSCC malignance remain elusive. We reveal that chronic arecoline exposure substantially induces upregulation of fat mass and obesity‐associated protein (FTO), MYC, and programmed cell death‐ligand 1 (PD‐L1) in OSCC cells. Moreover, upregulation of PD‐L1 is observed in OSCC cell lines and tissues and is associated with areca nut chewing in OSCC patients. We also demonstrate that arecoline‐induced FTO promotes the stability and expression levels of PD‐L1 transcripts through mediating m6A modification and MYC activity, respectively. PD‐L1 upregulation confers superior cell proliferation, migration, and resistance to T‐cell killing to OSCC cells. Blockage of PD‐L1 by administration of anti‐PD‐L1 antibody shrinks tumor size and improves mouse survival by elevating T‐cell‐mediated tumor cell killing. Therefore, targeting PD‐L1 might be a potential therapeutic strategy for treating PD‐L1‐positive OSCC patients, especially those with habitual areca nut chewing. [ABSTRACT FROM AUTHOR]

Objectives: Percutaneous nephrolithotomy and placement of nephrostomy tube are performed for renal stones >2 cm in diameter. Attempts have been made to infiltrate local anesthetics with or without adjuvants into the surgical site to reduce pain. We hypothesized that there would be a significant prolongation of the analgesic effect of local anesthetic instillation along the nephrostomy tube due to the adjuvant dexamethasone. Methods: After ethical approval and Clinical Trials Registry ‐ India registration (CTRI/2020/03/024332), 64 American Society of Anesthesiologists classification 1 and 2 adult patients were enrolled in this randomized double‐blinded prospective study divided into Group R—received 20 mL 0.2% Ropivacaine and Group R + D—received 20 mL 0.2% Ropivacaine with dexamethasone 8 mg, injected through a multi‐lumen wound infiltration catheter. Results: The demographic profile of patients was similar in both groups. The mean duration of analgesia was longer in Group R + D (21.3 ± 2.1 hrs) versus Group R (10 ± 1.9 hrs, P = 0.001). The mean numeric rating scale scores of Group R + D were significantly lower at all time intervals (P = 0.001). Also, the cumulative dose of ropivacaine and the total use of fentanyl postoperatively in Group R was much higher (70 ± 10.4 vs 56 ± 8.9 μg, P = 0.02). The C‐reactive protein levels were significantly lower in Group R + D (13.8 ± 1.5 vs 23.1 ± 1.2 mg/L, P = 0.001 and 16.5 ± 1.3 vs 28.5 ± 1.7 mg/L, P = 0.001, at 24 and 48 hrs, respectively). Conclusion: We conclude that dexamethasone can be used as a suitable adjuvant to intermittent local anesthetic infiltration after percutaneous nephrolithotomy with a nephrostomy tube for the prolongation of analgesia. [ABSTRACT FROM AUTHOR]

Background: In recent clinical practice, an increasing number of elderly patients suffering from head and neck squamous cell carcinoma (HNSCC) of unknown pathophysiology is observed. The majority of HNSCC patients can roughly be divided into three subcategories. First, a small group of young patients who present with variants of genomic aberrations and inheritable diseases like Fanconi anaemia. Second, an increasing population of HPV-related HNSCCs that are regarded as genomic stable tumours with a more favourable prognosis. Though HPV-related tumours used to be more common among younger males, a notable rise in the elderly population is observed. The third subcategory, that of HPV-negative tumours, has been shown to be more heterogeneous with involvement of a variety of oncogenic pathways related to lifestyle factors like smoking and alcohol consumption, often seen in middle-aged males. Some of these pathways could be related to age, such as TP53 alterations, EGFR activation, apoptotic pathway alterations and field cancerization. Conclusions: In this narrative review, we provide an overview of established and newly discovered age-specific pathophysiological mechanisms underlying HNSCC. We propose a fourth subcategory of patients with a suspected different pathophysiology: elderly (HPV-negative) HNSCC patients without a history of tobacco and alcohol consumption. In this subcategory, carcinogenesis seems to be a multi-step process based on genomic instability, immunosenescence, cell cycle disruption and telomere shortening. To conclude, we discuss suggestions for future research to fill the knowledge gap about age-dependent HNSCC carcinogenesis. [ABSTRACT FROM AUTHOR]

Background and Aims: Erector spinae plane (ESP) block is a simple and safe interfascial plane block reported to provide good analgesia after thoracolumbar surgeries. We compared its efficacy with conventional peritubal local anesthetic infiltration following percutaneous nephrolithotomy (PCNL). Material and Methods: A total of 60 adult patients posted for elective PCNL were randomly allocated into two groups. Postoperatively, Group I received ultrasound (US) guided peritubular infiltration block with 20 ml of 0.25% levobupivacaine and Group II received US guided ESP block with 20 ml of 0.25% levobupivacaine. The two groups were compared for the time to first rescue analgesic (Injection tramadol), number of rescue analgesic demands, total analgesic consumption in first 24 hours, VAS (rest and dynamic) scores and the adverse effects. The data were analyzed by unpaired t-test and Mann Whitney U test. Results: The time to first rescue analgesic demand was significantly longer in Group II (6.93 ± 2.15 h vs. 16.21 ± 7.53 h). The VAS scores (rest and dynamic) at eight and twelve hours of measurement were significantly lower in Group II (P < 0.05). The number of analgesic demands were less in group II (2.97 ± 0.49 vs. 1.00 ± 1.05). The total analgesic consumption in first 24 hours was less in Group II (148.33 ± 24.51 mg vs. 51.92 ± 45.78 mg). Conclusion: ESP block is a very effective and safe technique to provide prolonged duration of postoperative analgesia following PCNL. Peritubal local anesthetic infiltration is also a reliable technique for postoperative analgesia. [ABSTRACT FROM AUTHOR]

Despite advances in multimodal treatment for oral cavity squamous cell carcinoma, recurrence rates remain high, providing an opportunity for new therapeutic modalities that may improve oncologic outcomes. Much recent attention has been paid to the molecular interactions between the tumor cells with the adjacent peritumoral microenvironment, in which immunosuppressive molecular changes create a landscape that promotes tumor progression. The rationale for the introduction of immunotherapy is to reverse the balance of these immune interactions in a way that utilizes the host immune system to attack tumor cells. In the preoperative setting, immunotherapy has the advantage of priming the unresected tumor and the associated native immune infiltration, supercharging the adaptive anti-tumor immune response. It also provides the basis for scientific discovery where the molecular profile of responders can be interrogated to elucidate prognostic markers to aid in future patient selection. Preoperative immunotherapy is not without limitations. The risk of surgical delay due to immune adverse events must be carefully discussed by members of a multidisciplinary treatment team and patient selection will be critical. One day, the discovery of predictive biomarkers may allow for algorithms where pre-surgical immunotherapy decreases the size of surgical defect and impacts the intensity of adjuvant therapy leading to improved patient survival and decreased morbidity. With further study, immunotherapy could become a key component of future treatment algorithm. [ABSTRACT FROM AUTHOR]

Background: Lower prevalence HPV infection has been previously reported in Thai population when compared with Western countries. p16 expression indicates HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), but not non-OPSCC. We therefore evaluated the characteristic and association of p16 and HPV in Thai patients with HNSCC.Methods: We used immunohistochemistry and qPCR, respectively, to detect p16 and HPV DNA in archrival formalin-fixed paraffin-embedded HNSCC tissues. Patient characteristics and survival were analyzed.Results: p16 expression was detected in tumors of 72 of 662 (10.9%) patients with HNSCC and was significantly associated with higher-grade histology, advanced nodal stage, and oropharynx. p16 was expressed in 28 and 6.5% of patients with OPSCC or non-OPSCC, respectively, and HPV DNA was detected in 15.6 and 1% of patients, respectively. Using p16 as a surrogate for HPV status, sensitivities were 80 and 25% in OPSCC and non-OPSCC, respectively. Positive and negative predictive rates of OPSCC were 38 and 95%. Discordance rates between HPV and p16 were 23 and 7% in OPSCC and non-OPSCC, respectively. Overall survival (OS) were significantly longer in both p16-positive OPSCC (p = 0.049), and non-OPSCC (p = 0.003).Conclusions: Low prevalence of p16 and HPV associated OPSCC and non-OPSCC were confirmed in Thai patients. High discordance and low positive predictive rates of p16 were observed in HPV-associated OPSCC. p16 was a significant prognostic factor for OS for patients with OPSCC or non-OPSCC. Therefore, HPV testing should be performed to assess the association of HPV with HNSCC regardless of p16 expression. [ABSTRACT FROM AUTHOR]

Purpose: Immune scores have been used as a prognostic factor for various types of cancer. However, the association between immune scores and the prognosis of laryngeal squamous cell cancer (LSCC) has not yet been investigated. This study aimed to explore the prognostic significance of immune scores and construct a clinical nomogram to predict the survival of patients with LSCC. Methods: The clinicopathological characteristics and immune scores of 102 patients with LSCC were obtained from TCGA database and a nomogram was developed. C-index and calibration curves were applied to assess the performance of the model. Results: Patients with higher immune scores had significantly better overall survival (OS). The prognostic nomogram presented a good performance in survival prediction. Conclusions: High immune scores are correlated with improved OS in patients with LSCC. In addition, the nomogram developed for this study may assist clinicians in the prognostic evaluation of patients with LSCC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of nephrostomy tube type on postoperative pain and blood loss following percutaneous nephrolithotomy (PCNL). Methods: This is a prospective non-randomized study performed at Aga Khan University Hospital from July 2017 to June 2018. In this study we prospectively studied adult patients (16 to 65 years) who underwent unilateral PCNL. Patients who had nephrostomy with balloon (12Fr Foley's catheter) were compared with patients who had nephrostomy without balloon (12Fr Nelaton™ catheter). STONE Nephrolithometry score was used to assess the stone complexity. Mean pain score at six and 24 hours and mean hemoglobin drop at 24 hours was compared between two groups using independent sample t-test, p-value of <0.05 was considered significant. Results: Over one year, 198 PCNL were performed out of which 119 were included for analysis. Sixty-six had nephrostomy tube with balloon and 53 had nephrostomy tube without balloon. Mean STONE score (9.66±1.4 vs. 9.64±1.24) and operative time (72.84±28.34 vs. 86.05±32.1 minutes) was comparable. Mean postoperative pain score at 6 hours and 24 hours postoperative was significantly lower in balloon group as compared to without balloon group. Mean Hemoglobin drop was similar in both groups (p=0.60). Conclusion: The use of nephrostomy tube with balloon after PCNL as this is associated with less pain and comparable hemoglobin drop as compare to nephrostomy tube without balloon. [ABSTRACT FROM AUTHOR]

Background: Accumulation of immunosuppressive protein programmed death-ligand 1 (PD-L1) has been documented in several cancers and contributes to the evasion of the host immune system. However, cancer cell-intrinsic signaling-dependent control of PD-L1 expression remains to be elucidated. Herein, we aimed to identify the let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC). Methods: The expression of let-7 family and PD-L1 was quantified in HNSCC tissues and adjacent normal tissues. PD-L1 degradation was evaluated in HNSCC cells in response to elevated expressions of let-7a or let-7b. The regulation of let-7 family on PD-L1 degradation through a mechanism involving T-cell factor-4 (TCF-4) control of β-catenin/STT3 pathway was evaluated. Immune recognition of HNSCC in vivo was examined in subcutaneous tumor-bearing C3H mice in the presence of let-7a/b and/or CTLA-4 antibody. Results: The let-7 family were significantly down-regulated in the context of HNSCC, sharing a negative correlation with PD-L1 expression. Glycosylated PD-L1 was detected in HNSCC cells, which was reduced by let-7a/b over-expression. TCF-4, the target of let-7a/b, activated the β-catenin/STT3 pathway and promoted PD-L1 degradation. In vivo analysis demonstrated that let-7a/b over-expression potentiated anticancer immunotherapy by CTLA-4 blockade. Conclusions: Taken together, our findings highlight targeting let-7 family as a potential strategy to enhance immune checkpoint therapy for HNSCC. [ABSTRACT FROM AUTHOR]

Background: Biomarkers in head and neck squamous cell carcinoma (HNSCC) emerge rapidly in recent years, especially for new targeted therapies and immunotherapies. Methods: Recent, relevant peer‐reviewed evidence were critically reviewed and summarized. Results: This review article briefly introduces essential biomarker concepts, including purposes and classifications (predictive, prognostic, and diagnostic markers), and the phases of biomarker development. We summarize current biomarkers in order of clinical utility; p16 and human papillomavirus status remain the most important and validated biomarkers in HNSCC. The rationale for biomarker study design continues to evolve with technological advances, especially whole‐exome or whole‐genomic sequencing. Noninvasive body fluid and liquid biopsy biomarkers appear to hold strong potential for development as tools for early cancer detection, cancer diagnosis, monitoring of disease recurrence, and outcome prediction. In light of discrepancies among different technologies, standardized approaches are needed. Conclusion: Biomarkers from cancer tissue or blood in HNSCC could direct new anticancer therapies. [ABSTRACT FROM AUTHOR]

To evaluate the effect of quadratus lumborum block (QLB) for postoperative analgesia after percutaneous nephrolithotomy (PCNL), we searched Pubmed, Embase, Cochrane library, the Chinese Biomedical Literature Database, and randomized controlled trials (RCTs) assessing analgesic efficacy of QLB for PCNL are included in this meta-analysis. The related trials met the inclusion criteria were analyzed using RevMan 5.4 software, the weighted mean difference (WMD), with their corresponding 95% CI, was calculated to compare continuous variables. Nine RCTs are included in the meta-analysis showed that QLB group had significantly lower opioids consumption (WMD - 29.59 95% CI - 43.64 to - 15.55; P < 0.00001), lessen visual analog scale (VAS) after surgery 2 h (WMD - 1.35, 95% CI - 1.93 to - 0.76; P < 0.00001), 6 h (WMD - 1.47, 95% CI - 2.04 to - 0.91; P < 0.00001) 12 h (WMD - 1.75, 95% CI - 3.17 to - 0.32; P = 0.02) and 24 h (WMD - 1.4, 95% CI - 1.86 to - 0.94; P < 0.00001), shorter hospital stay(WMD - 0.7, 95% CI -1.26 to - 0.14, P < 0.00001) and reduce intestinal exhaust recovery time (WMD - 7.41, 95% CI - 9.36 to - 5.46, P < 0.00001) than in the control group. QLB offers some potential advantages in terms of opioids consumption, VAS, hospital stay and intestinal exhaust recovery time. However, good quality and large studies with long-term follow-up are warranted for further research., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Backgrounds: Human papilloma virus (HPV) infection is an important factor in development and prognosis of head and neck squamous cell carcinoma (HNSCC). It is also known that HPV infection could affect anti-cancer immunity. Methods: We examined the association between cancer immunity-related molecules and HPV infection, using immunohistochemical (IHC) staining for p16, PD-L1, and FOXP3 and real-time polymerase chain reaction for HPV. Results: The IHC staining for PD-L1 was positive in 30 out of 122 cases (24.6%) and p16 showed positivity in 68 out of 122 cases (55.7%). HPV was detected in 48 out of 122 cases (39.3%). P16 expression was significantly associated with PD-L1 expression (P=0.004), HPV infection (P=0.032), and the number of FOXP3-positive tumor infiltrating lymphocytes (P=0.009). PD-L1-positive or p16-positive HNSCC showed a worse prognosis than PD-L1-negative or p16-negative HNSCC. Conclusion: P16 expression may predict PD-L1 expression, and p16 expression may also be associated with the immune evasion of HNSCC. [ABSTRACT FROM AUTHOR]

Introduction: The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC. Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC. Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines. [ABSTRACT FROM AUTHOR]

Inflammation is deeply involved in the development of most types of cancer. Many studies focus on the interaction between immune-inflammatory mechanisms and tumorigenesis in the head and neck squamous cell carcinoma (HNSCC). In this chapter, we emphasize the complexity of processes underlying this interaction and discuss the mechanisms of carcinogenesis in HNSCC with a special focus on metabolic changes, inflammation, and the immune landscape. Unveiling complex connections between immuno-inflammatory processes and tumor initiation, promotion, and progression will open new directions in the reliable identification of predictive factors and therapeutic targets in HNSCC., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objectives: To assess the safety and efficacy of local anesthetic infiltration around nephrostomy tract on postoperative pain control after percutaneous nephrolithotomy. Methods: This systematic review was performed based on randomized clinic trials about local anesthetic infiltration around nephrostomy tract on postoperative pain control. The weighted mean difference (WMD), with their corresponding 95% CI, was calculated to compare continuous variables. Results: Our results showed that the consumption of analgesic was less in the experimental group than in the control group (WMD -25.32, 95% CI -48.09 to -2.55, p = 0.003). There was no significant difference between the mean Visual Analog Scale (VAS) in the experimental group than the control group after 6 h while significantly lower after 24 h. The time of first analgesic demand was significantly longer in the experimental group (WMD 2.19, 95% CI 0.98- 3.41). There was no significant difference between 2 groups in terms of operation time, hemoglobin (Hb) alteration, and hospital stay. Conclusion: Local anesthetic infiltration around nephrostomy tract had similar efficacy in the control group in terms of operation time, Hb alteration, and hospital stay, but offers some potential advantages in terms of analgesia requirement, the time of first analgesic demand, and VAS-24 h. However, good quality and large studies with long-term follow-up are warranted for further research. [ABSTRACT FROM AUTHOR]

Objective: To use alternative quantitation approaches to clarify the clinical implication of programmed cell death ligand 1 (PD-L1) in squamous cell carcinoma of the oral tongue (SCCOT)., Materials and Methods: Ventana SP263 immunohistochemistry assay and a multiplicative QuickScore method were applied to quantify PD-L1 in tumor and surrounding immune cells from 101 patients with SCCOT. Tumor-infiltrating immune cells were estimated from bulk tissue transcriptional profiles of 25 patients. Circulating PD-L1 levels were measured in serum from 30 patients using an electrochemiluminescence assay platform., Results: We found higher tumor cell PD-L1 levels in females than males (p = .019). For patients with low PD-L1 in tumor cells, better survival was seen in males than females (overall survival p = .021, disease-free survival p = .020). Tumor-infiltrating natural killer T cells, immature dendritic cells, and M1 macrophages were positively associated with tumor cell PD-L1 (p < .05)., Conclusions: Our data confirmed the significance of gender on tumor cell PD-L1 expression and demonstrated combined effects of gender and PD-L1 levels on clinical outcome in patients with SCCOT. The data also indicated the involvement of specific immune cell types in PD-L1-regulated immune evasion., (© 2020 The Authors. Oral Diseases published by John Wiley & Sons Ltd.)

An author index for the 2015 issue of the "BJU International" journal is presented.

Simple Summary: Head and neck cancer (HNC) is the sixth most common cancer, causing almost half a million deaths worldwide every year. The two subtypes of HNC are distinctly associated with smoking/drinking and/or human papillomavirus (HPV) infection. While the incidence of non-viral HNC is decreasing, HPV-positive HNC incidence has dramatically increased in the last few decades. Accumulating evidence from numerous studies shows molecular and clinical differences in mutations, gene expression regulation, treatment responses, and patient survival rates between HPV-positive and HPV-negative HNC. Here, we discuss the current status of HNC research and clinical approaches and suggest unanswered questions and future directions. Head and neck squamous cell carcinoma (HNSCC) is a unique malignancy associated with two distinct risk factors: exposure to typical carcinogens and infection of human papillomavirus (HPV). HPV encodes the potent oncoproteins E6 and E7, which bypass many important oncogenic processes and result in cancer development. In contrast, HPV-negative HNSCC is developed through multiple mutations in diverse oncogenic driver genes. While the risk factors associated with HPV-positive and HPV-negative HNSCCs are discrete, HNSCC patients still show highly complex molecular signatures, immune infiltrations, and treatment responses even within the same anatomical subtypes. Here, we summarize the current understanding of biological mechanisms, treatment approaches, and clinical outcomes in comparison between HPV-positive and -negative HNSCCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Among the over 200 human papillomavirus (HPV) genotypes identified, approximately 15 of them can cause human cancers. In this review, we provided an updated overview of the distribution of cancer-causing HPV genotypes by countries in East, Southeast and South Asia. Besides the standard screening and treatment methods employed in these regions, we unravel HPV detection methods and therapeutics utilised in certain countries that differ from other part of the world. The discrepancies may be partly due to health infrastructure, socio-economy and cultural diversities. Additionally, we highlighted the area lack of study, particularly on the oncogenicity of HPV genotype variants of high prevalence in these regions. Human papillomavirus (HPV) infection remains one of the most prominent cancer-causing DNA viruses, contributing to approximately 5% of human cancers. While association between HPV and cervical cancers has been well-established, evidence on the attribution of head and neck cancers (HNC) to HPV have been increasing in recent years. Among the cancer-causing HPV genotypes, HPV16 and 18 remain the major contributors to cancers across the globe. Nonetheless, the distribution of HPV genotypes in ethnically, geographically, and socio-economically diverse East, Southeast, and South Asia may differ from other parts of the world. In this review, we garner and provide updated insight into various aspects of HPV reported in recent years (2015–2021) in these regions. We included: (i) the HPV genotypes detected in normal cancers of the uterine cervix and head and neck, as well as the distribution of the HPV genotypes by geography and age groups; (ii) the laboratory diagnostic methods and treatment regimens used within these regions; and (iii) the oncogenic properties of HPV prototypes and their variants contributing to carcinogenesis. More importantly, we also unveil the similarities and discrepancies between these aspects, the areas lacking study, and the challenges faced in HPV studies. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease arising from the mucosa of the upper aerodigestive tract. Despite multimodality treatments approximately half of all patients with locally advanced disease relapse and the prognosis of patients with recurrent or metastatic HNSCC is dismal. The introduction of checkpoint inhibitors improved the treatment options for these patients and pembrolizumab alone or in combination with a platinum and fluorouracil is now the standard of care for first-line therapy. However, approximately only one third of unselected patients respond to this combination and the response rate to checkpoint inhibitors alone is even lower. This shows that there is an urgent need to improve prognostication and prediction of treatment benefits in patients with HNSCC. In this review, we summarize the most relevant risk factors in the field and discuss their roles and limitations. The human papilloma virus (HPV) status for patients with oropharyngeal cancer and the combined positive score are the only biomarkers consistently used in clinical routine. Other factors, such as the tumor mutational burden and the immune microenvironment have been highly studied and are promising but need validation in prospective trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer is a common malignancy with high morbidity and mortality. Tumor-infiltrating immune cells play key roles in its pathogenesis, influencing tumor behavior and evolution. The aim of our study was to assess the prognostic character of tumor-infiltrating CD4+, CD8+ and CD56+ cells in oral squamous cell carcinoma. We found major differences in CD4+ and CD8+ lymphocyte density at the front of invasion compared to the intratumor compartment. In addition, intense infiltration with CD8+ lymphocytes in both compartments carried a positive prognostic character. Moreover, we found that a higher intratumor infiltration with CD56+ cells significantly correlated with locoregional disease control and improved survival. Our study confirms the key role of innate and adaptive immune systems in oral squamous cell carcinoma. The predictive characteristics of CD8+ and CD56+ cells can be implemented as independent prognostic tools and can provide important elements in developing individualized therapy in the fight against oral cancer. (1) Background: The immune microenvironment plays an important role in carcinogenesis and has prognostic potential in many types of cancer. In this study we assess the prognostic character of tumor-infiltrating immune cells CD4+, CD8+ and CD56+ in resectable oral squamous cell carcinoma (OSCC); (2) Methods: We have evaluated the densities of CD4+, CD8+ and CD56+ in two distinct compartments, intratumor and invasion front, in 90 patients with OSCC; (3) Results: Significant differences were found between the tumor compartments for the CD4+ and CD8+ lymphocytes. An improved outcome (OS) was seen in patients with high densities of intratumor CD8+ lymphocytes (p = 0.0086), CD8+ lymphocytes at the front of invasion (p = 0.0011) and for intratumor CD56+ cells (p = 0.0016). Multivariate analysis confirmed the independent prognostic role of CD8+ at the front of invasion (OR = 3.75, CI95% 1.17–12.35, p = 0.026) and for intratumor CD56+ cells (OR = 3.669, CI95% 1.09–15.37, p = 0.035); (4) Conclusions: Tumor-infiltrating CD8+ lymphocytes at the front of invasion and CD56+ in the intratumor compartment display predictive traits in OSCC. A reach immune infiltration with these types of cells is associated with an improved patient outcome. [ABSTRACT FROM AUTHOR]

The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36–0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34–0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4–0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34–0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16–0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10–0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Squamous cell cancer of the head and neck is a common malignancy with poor prognosis. Despite the success of PD-L1 expression, the landscape of diagnostic, prognostic, and predictive biomarkers has delivered limited contributions to the clinic in the last decade. The dissection of the immunological landscape through investigation of the immune infiltrate, blood-based biomarkers, and genetic profiling has shown substantial scientific potential but all are yet to be validated. Further exploration is warranted though implementation of biomarkers. This should ideally be performed through prospective studies using standardized methods with harmonization of technical requirements. This review serves as a comprehensive overview for state-of-the-art knowledge and biomarkers in squamous cell cancer of the head and neck (SCCHN) that may prove their worth in future clinical practice. The era of immune checkpoint inhibitors has altered the therapeutic landscape in squamous cell cancer of the head and neck (SCCHN). Our knowledge about the tumor microenvironment has fueled the research in SCCHN, leading to several well-known and less-known prognostic and predictive biomarkers. The clinical staging, p16/HPV status, and PD-L1 expression are currently the main tools for assessing the patients' diagnosis and prognosis. However, several novel biomarkers have been thoroughly investigated, some reaching actual significant clinical contributions. The untangling of the immune infiltrate with the subtyping of tissue-associated tumor infiltrating lymphocytes, tumor-associated macrophages, and circulating blood-based biomarkers are an interesting avenue to be further explored and prospectively assessed. Although PD-L1 expression remains the most important response predictor for immune checkpoint inhibitors, several flaws impede proper assessment such as technical issues, different scoring protocol, and intra-, inter-, and temporal heterogeneity. In addition, the construction of an immune-related gene panel has been proposed as a prognostic and predictive stratification but lacks consensus. Recently, the role of microbioma have also been explored regarding its systemic and antitumor immunity. This review gives a comprehensive overview of the aforementioned topics in SCCHN. To this end, the integration of these clinically advantageous biomarkers via construction of an immunogram or nomogram could be an invaluable tool for SCCHN in future prospects. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor infiltrating lymphocytes (TILs) have been demonstrated as prognostic biomarkers in multiple cancer types. Among the various TIL phenotypic sub-populations, T-cells are most abundant. Several studies have investigated the prognostic value of CD4+ and CD8+ T-cell TILs in head and neck squamous cell carcinoma (HNSCC). In this study we performed a systematic review and meta-analysis of available evidence for CD4+ and CD8+ TIL biomarkers in HNSCC. The primary aim was to investigate the correlation of TIL sub-population levels and overall survival in HNSCC anatomical sub-sites. We demonstrate for the first time that tumor location has a significant impact upon the prognostic utility of CD4+ and CD8+ TILs in HNSCC. Such data is of critical importance when incorporating TIL biomarkers into current prognostic models and clinical practice. Objective: It has been suggested that the presence of tumor-infiltrating lymphocytes (TILs) in the tumor microenvironment is associated with a better prognosis in different types of cancer. In this systematic review and meta-analysis, we investigated the prognostic role of CD4+ and CD8+ TILs in head and neck squamous cell carcinoma (HNSCC). Methods: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched up to September 2020. This study was conducted following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Risk ratios from individual studies were displayed in forest plots and the pooled hazard ratios (HR) of death and corresponding confidence intervals (CI) were calculated according to random-effects models. Risk of bias of the included studies was assessed through the Newcastle–Ottawa scale. Results: 28 studies met the inclusion criteria. Studies conducted on HNSCC subsites combined reported a significant reduction in the risk of death for both high CD4+ (HR: 0.77; 95% CI: 0.65–0.93) and high CD8+ TILs (HR: 0.64; 95% CI: 0.47–0.88). High CD4+ TILs were associated with significantly better overall survival among oropharyngeal HNSCC (HR: 0.52; 95% CI: 0.31–0.89), as well as high CD8+ TILS in Human papillomavirus −ve and +ve cancers (HR: 0.39; 95% CI: 0.16–0.93 and HR: 0.40; 95% CI 0.21–0.76 respectively). CD8+ TILs were also associated with improved survival in hypopharyngeal cancers (HR = 0.43 CI: 0.30–0.63). No significant association emerged for patients with cancer of the oral cavity or larynx. Conclusions: The findings from this meta-analysis demonstrate the prognostic significance of CD8+ and CD4+ TILs in HNSCC and variation in tumor subsite warrants further focused investigation. We highlight how TILs may serve as predictive biomarkers to risk stratify patients into treatment groups, with applications in immune-checkpoint inhibitors notable areas for further research. [ABSTRACT FROM AUTHOR]

Recurrent locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with dismal prognosis because of its highly invasive behavior and resistance to conventional intensive chemotherapy. The combination of targeted therapy and conventional chemotherapy has significantly improved clinical outcomes. In recent years, the development of immunotherapies, such as immune checkpoint inhibitors (ICIs), has further increased treatment responses and prolonged survival. However, the limited response rate, risk of immunotherapy-related adverse effects and high cost of immunotherapy make the identification of predictive markers to optimize treatment efficacy a critical issue. Biomarkers are biological molecules that have been widely utilized to predict treatment response to certain treatments and clinical outcomes or to detect disease. An ideal biomarker should exhibit good predictive ability, which can guide healthcare professionals to achieve optimal treatment goals and bring clinical benefit to patients. In this review, we summarized the results of recent and important studies focused on HNSCC ICI immunotherapy and discussed potential biomarkers including their strengths and limitations, aiming to gain more insight into HNSCC immunotherapy in real world clinical practice. [ABSTRACT FROM AUTHOR]

Cancers of the oral cavity cause significant cancer-related death worldwide. While survival rates have improved in recent years, new methods of treatment are being investigated to limit disease progression and to improve outcomes, particularly in oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). The emerging treatment modality of immunotherapy targets immune checkpoint molecules including PD-1 and its ligand PD-L1, CTLA-4, LAG-3, and TIM-3 to enhance the host immune response against tumours, and to limit the growth and progression of cancer cells. In this systematic review, we searched five databases for keywords pertaining to oral cancers and OPMDs, along with immune checkpoint inhibitors, in order to summarize the current status of their use and efficacy in these diseases. A total of 644 different articles were identified between 2004 and 2019, with 76 deemed suitable for inclusion in the study, providing a total of 8826 samples. Combined results show expression of PD-1 and PD-L1 in the majority of OPMD and OSCC samples, with expression correlating with increased progression and decreased survival rates. Immunotherapy agents pembrolizumab and nivolumab target PD-1 and have been shown to prolong survival rates and improve disease outcomes, especially in combination with chemotherapy or radiotherapy. Despite the equivocal nature of current evidence, there is support for the prognostic and predictive value of immune checkpoint molecules, especially PD-L1, and many studies provide support for the effective use of immune checkpoint inhibitors in the management of OSCC. Limited data is available for OPMD, therefore this should be the focus of future research. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinomas (HNSCC) are one of the most prevalent cancers worldwide. Active human papillomavirus (HPV) infection has been identified as an important additional risk factor and seems to be associated with a better prognosis in non-drinker and non-smoker young patients with oropharyngeal SCC. The better response of the immune system against the HPV-induced HNSCC is suspected as a potential explanation for the better prognosis of young patients. To further assess this hypothesis, our review aims to shed light the current knowledge about the impact of HPV infection on the immune response in the context of HNSCC, focusing on the innate immune system, particularly highlighting the role of macrophages, Langerhans and myeloid cells, and on the adaptative immune system, pointing out the involvement of T regulatory, T CD8 and T CD4 lymphocytes. In addition, we also review the preventive (HPV vaccines) and therapeutic (checkpoint inhibitors) strategies against HPV-related HNSCC, stressing the use of anti-CTLA4, PD-L1, PD-L2 antibodies alone and in combination with other agents able to modulate immune responses. [ABSTRACT FROM AUTHOR]