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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.

Human papillomavirus (HPV) is a factor in oropharyngeal cancer, but data regarding other head and neck locations are scarce in France. The main objective of the study was to determine the prevalence of HPV in head and neck cancers at all locations. As a secondary objective, we aimed to investigate the HPV genotypes. We retrospectively included in a tertiary center between 2014 and 2020 mucosal squamous cell carcinomas of the head and neck in adult. First outcome was the prevalence of HPV cancer. Secondary outcomes were overall survival (OS) at 2 and 5 years and disease-free survival (DFS). A total of 508 patients were enrolled, resulting in 537 cases of mucous squamous cell carcinoma of the head and neck (n = 29 synchronous carcinomas). Clinical, pathological, and survival data were collected, and a double PCR for HPV with genotyping was performed on most of the samples. The HPV prevalence in the cohort was 28.2%, with HPV 16 being the predominant genotype (87%). However, HPV-positive status did not significantly improve OS at 2 and 5 years or DFS (P = 0.1, P = 0.64, and P = 0.07, respectively). It was also observed that HPV-positive patients had significantly fewer second tumor localizations (P < 0.01). The prevalence of HPV continues to rise, and the complexities surrounding HPV status and its association with clinical outcomes in head and neck squamous cell carcinoma highlight the impact of vaccination., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

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.)

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., (© 2022 The Japanese Urological Association.)

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., (© 2022. Springer Nature Switzerland AG.)

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.

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.)

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.)

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., (© 2019 Wiley Periodicals, Inc.)