Research

9 pages, 1243 KiB

Open AccessCommunication

Beneficial Effect of Metformin on the Five-Year Survival in about 40,000 Patients with Head and Neck Cancer

by Florian Gaertner, Saskia Preissner, Max Heiland, Robert Preissner and Jonas Wüster

Cancers 2024, 16(5), 982; https://doi.org/10.3390/cancers16050982 - 28 Feb 2024

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Introduction: Even in times of new therapy regimes, the overall survival of patients with head and neck cancer remains low. Since the previous studies showed the beneficial effect of metformin medication on the survival of patients with cancer, our objective was to investigate [...] Read more.

Introduction: Even in times of new therapy regimes, the overall survival of patients with head and neck cancer remains low. Since the previous studies showed the beneficial effect of metformin medication on the survival of patients with cancer, our objective was to investigate if—and in which way—metformin medication affects the overall survival of patients with head and neck cancer. Methods: Clinical data pertaining to patients diagnosed with head and neck cancer (International Classification of Diseases 10 codes C00-C14, C31, and C32) were retrospectively retrieved from the TriNetX network (TriNetX, Cambridge, MA, USA). The initial cohort extracted from the network was stratified into two groups: patients on metformin medication (cohort I), and individuals not on metformin medication (cohort II). The matching criteria included age, gender, BMI, type 2 diabetes, and risk factors, such as nicotine and alcohol abuse/dependence. Kaplan–Meier analysis, risk analysis, and the calculation of odds and hazard ratios were conducted. Additionally, the Hemoglobin A1c values were subject to analysis. Results: Following matching, each cohort comprised 20,416 patients. Cohort I exhibited a higher five-year survival rate at 75.3%, in contrast to cohort II, which registered a rate of 69.8%. The odds ratio was 0.79 (95% CI = 0.75–0.83), and the hazard ratio was 0.78 (95% CI = 0.75–0.82). Conclusion: Metformin medication may correlate with improved five-year survival rates in patients with head and neck cancer. Since potentially influencing factors such as comorbidities and the initial tumor stage were not available, the results of our retrospectively conducted study must be interpreted with caution. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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23 pages, 27961 KiB

Open AccessArticle

Optimization of a Three-Dimensional Culturing Method for Assessing the Impact of Cisplatin on Notch Signaling in Head and Neck Squamous Cell Carcinoma (HNSCC)

by Alinda Anameriç, Arkadiusz Czerwonka and Matthias Nees

Cancers 2023, 15(22), 5320; https://doi.org/10.3390/cancers15225320 - 07 Nov 2023

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Abstract

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer type, with cisplatin being a primary treatment approach. However, drug resistance and therapy failure pose a significant challenge, affecting nearly 50% of patients over time. This research had two aims: (1) to [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer type, with cisplatin being a primary treatment approach. However, drug resistance and therapy failure pose a significant challenge, affecting nearly 50% of patients over time. This research had two aims: (1) to optimize a 3D cell-culture method for assessing the interplay between tumor cells and cancer-associated fibroblasts (CAFs) in vitro; and (2) to study how cisplatin impacts the Notch pathway, particularly considering the role of CAFs. Using our optimized “3D sheet model” approach, we tested two HNSCC cell lines with different cisplatin sensitivities and moderate, non-mutated NOTCH1 and -3 expressions. Combining cisplatin with a γ-secretase inhibitor (crenigacestat) increased sensitivity and induced cell death in the less sensitive cell line, while cisplatin alone was more effective in the moderately sensitive line and sensitivity decreased with the Notch inhibitor. Cisplatin boosted the expression of core Notch signaling proteins in 3D monocultures of both lines, which was counteracted by crenigacestat. In contrast, the presence of patient-derived CAFs mitigated effects and protected both cell lines from cisplatin toxicity. Elevated NOTCH1 and NOTCH3 protein levels were consistently correlated with reduced cisplatin sensitivity and increased cell survival. Additionally, the Notch ligand JAG2 had additional, protective effects reducing cell death from cisplatin exposure. In summary, we observed an inverse relationship between NOTCH1 and NOTCH3 levels and cisplatin responsiveness, overall protective effects by CAFs, and a potential link between JAG2 expression with tumor cell survival. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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10 pages, 672 KiB

Open AccessArticle

Associations of Head and Neck Cancer with Hepatitis B Virus and Hepatitis C Virus Infection

by Shih-Han Hung, Tzong-Hann Yang, Yen-Fu Cheng, Chin-Shyan Chen and Herng-Ching Lin

Cancers 2023, 15(18), 4510; https://doi.org/10.3390/cancers15184510 - 11 Sep 2023

Cited by 1 | Viewed by 981

Abstract

This case-control study investigates the associations between head and neck cancer (HNC), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. We included 5603 patients who had received a diagnosis of HNC as cases and 16,809 propensity score matching controls. We employed [...] Read more.

This case-control study investigates the associations between head and neck cancer (HNC), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection. We included 5603 patients who had received a diagnosis of HNC as cases and 16,809 propensity score matching controls. We employed multivariate logistic regression models to evaluate the association of HNC with HBV and HCV infection after taking sociodemographic characteristics and diabetes, hypertension, hyperlipidemia, HPV infection, tobacco use disorder, and alcohol abuse/alcohol dependence syndrome into considerations. Results show that 7.9% of the total sample had been previously diagnosed with HBV infection, with 9.0% prevalence among cases and 7.6% among controls (p < 0.001). The chi-squared test suggests a significant difference in the prevalence of HCV infection between cases and controls (3.3% vs. 2.7%, p = 0.019). The covariate-adjusted odds ratio (OR) of HBV infection in patients with HNC relative to controls was 1.219 (95% CI = 1.093~1.359). Additionally, the adjusted OR of HCV infection in patients with HNC was 1.221 (95% CI = 1.023~1.457) compared to controls. Furthermore, patients with oropharyngeal cancer were more likely to have HCV infection than controls (adjusted OR = 2.142, 95% CI = 1.171~3.918). Our study provides evidence that suggests a potential association between HBV and HCV infections and the risk of HNC. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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18 pages, 860 KiB

Open AccessArticle

Is High-Risk Sexual Behavior a Risk Factor for Oropharyngeal Cancer?

by Gunnar Wichmann, Jasmin Rudolph, Sylvia Henger, Christoph Engel, Kerstin Wirkner, John Ross Wenning, Samira Zeynalova, Susanne Wiegand, Markus Loeffler, Theresa Wald and Andreas Dietz

Cancers 2023, 15(13), 3356; https://doi.org/10.3390/cancers15133356 - 26 Jun 2023

Cited by 2 | Viewed by 3440

Abstract

(1) Background: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). A highly influential case-control study by [...] Read more.

(1) Background: Several lines of evidence established a link between high-risk (HR) sexual behavior (SB), the persistence of human papillomavirus (HPV) DNA in saliva, and the presence of oncogenic HR-HPV subtypes in oropharyngeal squamous cell carcinoma (OPSCC). A highly influential case-control study by D’Souza et al. comparing OPSCC patients and ENT patients with benign diseases (hospital controls) established HR-SB as a putative etiological risk factor for OPSCC. Aiming to replicate their findings in a nested case-control study of OPSCC patients and propensity score (PS)-matched unaffected controls from a large population-based German cohort study, we here demonstrate discrepant findings regarding HR-SB in OPSCC. (2) Methods: According to the main risk factors for HNSCC (age, sex, tobacco smoking, and alcohol consumption) PS-matched healthy controls invited from the population-based cohort study LIFE and HNSCC (including OPSCC) patients underwent interviews, using AUDIT and Fagerström, as well as questionnaires asking for SB categories as published. Afterwards, by newly calculating PSs for the same four risk factors, we matched each OPSCC patient with two healthy controls and compared responses utilizing chi-squared tests and logistic regression. (3) Results: The HNSCC patients and controls showed significant differences in sex distribution, chronologic age, tobacco-smoking history (pack years), and alcohol dependence (based on AUDIT score). However, PS-matching decreased the differences between OPSCC patients and controls substantially. Despite confirming that OPSCC patients were more likely to self-report their first sexual intercourse before age 18, we found no association between OPSCC and HR-SB, neither for practicing oral-sex, having an increased number of oral- or vaginal-sex partners, nor for having casual sex or having any sexually transmitted disease. (4) Conclusions: Our data, by showing a low prevalence of HR-SB in OPSCC patients, confirm findings from other European studies that differ substantially from North American case-control studies. HR-SB alone may not add excess risk for developing OPSCC. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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16 pages, 4174 KiB

Open AccessArticle

A Novel Role for the Soluble Isoform of CTLA-4 in Normal, Dysplastic and Neoplastic Oral and Oropharyngeal Epithelia

by Prarthna Clare, Farah Al-Fatyan, Badri Risheh, Kristine Nellany, Frank James Ward and Rasha Abu-Eid

Cancers 2023, 15(6), 1696; https://doi.org/10.3390/cancers15061696 - 10 Mar 2023

Cited by 3 | Viewed by 1755

Abstract

Background: Head and neck cancer (HNC) has a high mortality rate, with late diagnosis remaining the most important factor affecting patient survival. Therefore, it is imperative to identify markers that aid in early detection and prediction of disease progression. HNCs evade the [...] Read more.

Background: Head and neck cancer (HNC) has a high mortality rate, with late diagnosis remaining the most important factor affecting patient survival. Therefore, it is imperative to identify markers that aid in early detection and prediction of disease progression. HNCs evade the immune system by different mechanisms, including immune checkpoints. Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) is an immune checkpoint receptor that downregulates anti-tumour immune responses, with evidence of involvement in HNC. The less studied, alternatively spliced, soluble isoform (sCTLA-4) also plays an immunosuppressive role that contributes to immune escape. We quantified sCTLA-4 in normal, potentially malignant, and malignant oral and oropharyngeal tissues to elucidate any role in tumourigenesis and identify its potential as a biomarker for diagnosis and patient stratification. Methods: Normal, low- and high-grade epithelial dysplasia, and squamous cell carcinoma oral and oropharyngeal biopsies were selectively stained for sCTLA-4 and quantified using the image analysis software QuPath. Results: Distinct sCTLA-4 staining patterns were observed, in which normal epithelial sCTLA-4 expression correlated with keratinocyte differentiation, while disrupted expression, both in intensity and localisation, was observed in dysplastic and neoplastic tissues. Conclusions: Our data indicate an additional, previously unknown role for sCTLA-4 in epithelial cell differentiation and proliferation. Furthermore, our findings suggest the potential of sCTLA-4 as a biomarker for predicting disease progression and patient stratification for targeted HNC therapies. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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13 pages, 1418 KiB

Open AccessArticle

Salivary Interleukin Levels in Oral Squamous Cell Carcinoma and Oral Epithelial Dysplasia: Findings from a Sri Lankan Study

by Nadisha S. Piyarathne, Manjula M. Weerasekera, Pasquel Fonsekalage Damith Fonseka, Appu Hennedi Thotahewage Sunil Karunatilleke, Rubasinha Liyanage Pemith Ranura Liyanage, Ruwan Duminda Jayasinghe, Kanishka De Silva, Surangi Yasawardene, Ekta Gupta, Jayasinghe Arachchilage Premasiri Jayasinghe and Rasha Abu-Eid

Cancers 2023, 15(5), 1510; https://doi.org/10.3390/cancers15051510 - 28 Feb 2023

Cited by 3 | Viewed by 1754

Abstract

The incidence of oral squamous cell carcinoma (OSCC), and its precursor, oral epithelial dysplasia (OED), is on the rise, especially in South Asia. OSCC is the leading cancer in males in Sri Lanka, with >80% diagnosed at advanced clinical stages. Early detection is [...] Read more.

The incidence of oral squamous cell carcinoma (OSCC), and its precursor, oral epithelial dysplasia (OED), is on the rise, especially in South Asia. OSCC is the leading cancer in males in Sri Lanka, with >80% diagnosed at advanced clinical stages. Early detection is paramount to improve patient outcome, and saliva testing is a promising non-invasive tool. The aim of this study was to assess salivary interleukins (lL1β, IL6, and IL8) in OSCC, OED and disease-free controls in a Sri Lankan study cohort. A case-control study with OSCC (n = 37), OED (n = 30) patients and disease-free controls (n = 30) was conducted. Salivary lL1β, IL6, and IL8 were quantified using enzyme-linked immuno-sorbent assay. Comparisons between different diagnostic groups and potential correlations to risk factors were assessed. Salivary levels for the three tested interleukins increased from disease-free controls through OED, and were highest in OSCC samples. Furthermore, the levels of IL1β, IL6, and IL8 increased progressively with OED grade. The discrimination between patients (OSCC and OED) and controls, as assessed by AUC of receiver operating characteristic curves, was 0.9 for IL8 (p = 0.0001) and 0.8 for IL6 (p = 0.0001), while IL1β differentiated OSCC from controls (AUC 0.7, p = 0.006). No significant associations were found between salivary interleukin levels and smoking, alcohol, and betel quid risk factors. Our findings suggest that salivary IL1β, IL6, and IL8 are associated with disease severity of OED, and are potential biomarkers for predicting disease progression in OED, and the screening of OSCC. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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15 pages, 1437 KiB

Open AccessArticle

Role of SAMITAL in the Prevention and Treatment of Chemo-Radiotherapy-Induced Oral Mucositis in Head and Neck Carcinoma: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Clinical Trial (ROSAM)

by Elena Fasanaro, Paola Del Bianco, Elena Groff, Antonella Riva, Giovanna Petrangolini, Fabio Busato, Paola Stritoni, Giovanni Scarzello, Lucio Loreggian and Gian Luca De Salvo

Cancers 2022, 14(24), 6192; https://doi.org/10.3390/cancers14246192 - 15 Dec 2022

Cited by 1 | Viewed by 1648

Abstract

Background: In patients affected by head and neck squamous cell carcinoma, the onset of severe oral mucositis is a decisive factor in completing concurrent chemo-radiotherapy, and few interventions have demonstrated a modest benefit. The primary aim of this clinical study was to evaluate [...] Read more.

Background: In patients affected by head and neck squamous cell carcinoma, the onset of severe oral mucositis is a decisive factor in completing concurrent chemo-radiotherapy, and few interventions have demonstrated a modest benefit. The primary aim of this clinical study was to evaluate the role of SAMITAL in reducing the incidence of severe mucositis induced by concurrent chemo-radiotherapy; the secondary aims were the tolerability and patient-reported quality of life measures. Methods: Patients were randomized to receive SAMITAL granules for oral suspension of 20 mL, four-time daily or matching placebo in a 1:1 fashion using a stratified-block randomization scheme by disease site and type of chemotherapy. The SAMITAL/placebo was dispensed at the baseline visit and at each weekly visit following radiotherapy initiation. Patients were subjected to weekly endoscopic evaluations to assess the presence of mucositis. In addition, patient-reported outcomes were measured. Results: Among the 116 patients treated with a median total dose of 66 Gy, 59 were randomized to SAMITAL and 57 to placebo. Overall, the incidence of severe mucositis was 51.7%, with 45.8% in the SAMITAL and 57.9% in the placebo arm (OR = 0.6; 95% CI: 0.3–1.3). After chemo-radiotherapy, patients randomized to SAMITAL reported significantly lower xerostomia, coughing and swallowing scores and a better quality of life. Conclusion: SAMITAL did not significantly reduce the incidence of severe mucositis in all studied populations. However, the lower rate of mucositis, together with a significantly better quality of life, suggested that a clinical benefit existed. This trial is registered with the EU Clinical Trials Register database, number 2012-002046-20, and with ClinicalTrials.gov, NCT01941992. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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Review

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14 pages, 329 KiB

Open AccessReview

Clinical Advances and Future Directions of Oncolytic Virotherapy for Head and Neck Cancer

by Zhan Wang, Peng Sun, Zhiyong Li and Shaowen Xiao

Cancers 2023, 15(21), 5291; https://doi.org/10.3390/cancers15215291 - 04 Nov 2023

Cited by 2 | Viewed by 3574

Abstract

Oncolytic viruses (OVs), without harming normal tissues, selectively infect and replicate within tumor cells, to release immune molecules and tumor antigens, achieving immune-mediated destruction of tumors and making them one of the most promising immunotherapies for cancer. Many clinical studies have demonstrated that [...] Read more.

Oncolytic viruses (OVs), without harming normal tissues, selectively infect and replicate within tumor cells, to release immune molecules and tumor antigens, achieving immune-mediated destruction of tumors and making them one of the most promising immunotherapies for cancer. Many clinical studies have demonstrated that OVs can provide clinical benefits for patients with different types of tumors, at various stages, including metastatic and previously untreatable cases. When OVs are used in combination with chemotherapy, radiotherapy, immunotherapy, and other treatments, they can synergistically enhance the therapeutic effects. The concept of oncolytic virotherapy (OVT) was proposed in the early 20th century. With advancements in genetic engineering, genetically modified viruses can further enhance the efficacy of cancer immunotherapy. In recent years, global research on OV treatment of malignant tumors has increased dramatically. This article comprehensively reviews the findings from relevant research and clinical trials, providing an overview of the development of OVT and its application in the clinical treatment of head and neck cancer. The aim is to offer insights for future clinical and fundamental research on OVT. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

14 pages, 946 KiB

Open AccessReview

The Inconsistent Assessment of Quality of Life in Patients Treated for Head and Neck Cancer with Anti-EGFR Inhibitors: A Systematic Scoping Review

by Sarah R. Sutton, April N. Taniguchi, Shaun A. Nguyen, William G. Albergotti, John M. Kaczmar, Alexandra E. Kejner and Jason G. Newman

Cancers 2023, 15(9), 2475; https://doi.org/10.3390/cancers15092475 - 26 Apr 2023

Viewed by 1157

Abstract

In patients receiving treatment for head and neck cancer (HNC), there is a correlation between quality of life (QoL) scores and treatment outcomes. Higher QoL scores have been associated with improved survival. Despite this, the assessment of QoL in clinical trials varies considerably. [...] Read more.

In patients receiving treatment for head and neck cancer (HNC), there is a correlation between quality of life (QoL) scores and treatment outcomes. Higher QoL scores have been associated with improved survival. Despite this, the assessment of QoL in clinical trials varies considerably. Three databases (Scopus, PubMed, and Cinahl) were queried for articles published in English between 2006 and 2022. Two reviewers (SRS and ANT) performed study screening, data extraction, and risk of bias assessment. The authors identified 21 articles that met the inclusion criteria. A total of 5961 patients were evaluated. QoL was reported as average scores for specific variables across five different surveys in 12 included articles. Supplemental QoL data were available in 10 included studies. Critical appraisal of studies indicated a high risk of bias due to the inclusion of trials. There is no standard method for reporting QoL data in clinical trials for HNC patients undergoing treatment with anti-EGFR inhibitors. Future clinical trials should standardize their method for assessing and reporting quality-of-life data to increase patient-centered care and refine treatment choices to optimize survival. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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14 pages, 533 KiB

Open AccessSystematic Review

Review of RM-1929 Near-Infrared Photoimmunotherapy Clinical Efficacy for Unresectable and/or Recurrent Head and Neck Squamous Cell Carcinoma

by Nanami L. Miyazaki, Aki Furusawa, Peter L. Choyke and Hisataka Kobayashi

Cancers 2023, 15(21), 5117; https://doi.org/10.3390/cancers15215117 - 24 Oct 2023

Cited by 4 | Viewed by 1223

Abstract

Head and neck squamous cell carcinoma (HNSCC) contribute to a significant global cancer burden. Developments in current therapeutic approaches have improved patient outcomes but have limited efficacy in patients with unresectable and/or recurrent HNSCC. RM-1929 near-infrared photoimmunotherapy (NIR-PIT) is an emerging treatment that [...] Read more.

Head and neck squamous cell carcinoma (HNSCC) contribute to a significant global cancer burden. Developments in current therapeutic approaches have improved patient outcomes but have limited efficacy in patients with unresectable and/or recurrent HNSCC. RM-1929 near-infrared photoimmunotherapy (NIR-PIT) is an emerging treatment that is currently being investigated in a Phase III clinical trial and has been conditionally approved for the treatment of unresectable and/or recurrent HNSCC in Japan. Here, we collect a series of case reports and clinical trial data to assess the efficacy of RM-1929 NIR-PIT. Disease control rates ranged from 66.7 to 100% across these studies, and overall response rates ranged from 43.3 to 100%, suggesting positive clinical outcomes. Low-grade postoperative localized pain and edema were the most frequently reported side effects, and preliminary reports on quality of life and pain levels suggest that RM-1929 NIR-PIT does not significantly decrease quality of life and is manageable with existing pain management strategies, including opioids. These preliminary data in real-world use of RM-1929 NIR-PIT show that it is a well-tolerated therapy that has clinically meaningful outcomes for patients with unresectable and/or recurrent HNSCC. Full article

(This article belongs to the Special Issue Advances in Head and Neck Cancer Research)

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