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Special Issue "New Frontiers in Head and Neck Oncology"

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A special issue of Current Oncology (ISSN 1718-7729). This special issue belongs to the section "Head and Neck Oncology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 25250

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Special Issue Editors

Dr. George Shenouda
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Guest Editor

Department of Radiation Oncology, McGill University Health Centre, Montréal, QC, Canada
Interests: head and neck oncology; brain tumors

Prof. Dr. Denis Soulieres

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Centre de recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM) and Institut du cancer de Montréal, Montréal, Québec, Canada
Interests: HNSCC; immunotherapy; biomarkers; mRCC; targeted therapy; DPYD
Special Issues, Collections and Topics in MDPI journals

Dr. Houda Bahig

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Associate Professor, Radiation Oncology, Universite de Montreal, Quebec, Canada
Interests: HNSCC; translational research; pharmacogenomics

Special Issue Information

Dear Colleagues,

The field of head and neck oncology is evolving very rapidly. The importance of achieving an uncomplicated cure has become very clear to all healthcare professionals in this area. Moreover, the continuously increasing incidence of HPV-related oropharyngeal cancer in young and usually healthy patients has stimulated significant clinical research to de-intensify treatment in current clinical trials around the world. At the same time, there is an increase in life expectancy and patients presenting with curable disease in their seventies and eighties. New therapeutic approaches are needed to provide adequate therapy in the context of treatment-related side effects. This is another area of urgent research to achieve a better therapeutic ratio without increasing patients’ symptoms burden. In addition, the importance of patient-reported outcomes (PRO) and QOL are essential components of all attempts to better understand the impact of treatment on patients and how we can improve their experience.

Dr. George Shenouda
Prof. Dr. Denis Soulieres
Dr. Houda Bahig
Guest Editors

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Keywords

Head and neck cancer
Oropharyngeal HPV-related cancer
Treatment de-intensification
Patient-reported outcomes
Quality of Life

Published Papers (12 papers)

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11 pages, 3855 KiB

Open AccessArticle

CD8+ T Cells and PD-L1 Expression as Prognostic Indicators in a Low Prevalence of HPV-Associated Oropharyngeal Squamous Cell Carcinoma

Kawita Atipas

Natthawadee Laokulrath

Janjira Petsuksiri

Narin Ratanaprasert

and

Warut Pongsapich

Curr. Oncol. 2023, 30(2), 1450-1460; https://doi.org/10.3390/curroncol30020111 - 20 Jan 2023

Cited by 1 | Viewed by 1381

Abstract

Human papillomavirus (HPV) infection detected in oropharyngeal squamous cell carcinoma (OPSCC) is associated with a better survival outcome from previous literature. However, Thailand and several Asian countries have a low prevalence of HPV-associated OPSCC and, therefore, have a low positive rate of immunostaining with p16. Tumor microenvironments (TME), including tumor-infiltrating CD8+ lymphocytes (CD8+ TIL) and programmed death ligand 1 (PD-L1), are proposed as significant prognostic indicators in addition to p16. Objectives: Explore the expression p16, CD8+ TIL, and PD-L1 and its value as prognostic indicators for overall survival (OS) in patients with OPSCC. Materials and Methods: Data from patients with OPSCC diagnosed from 2012 to 2018 were recovered from medical records and national registry. All available glass slides and slides of immunohistochemistry (IHC) of p16, CD8, and PD-L1 were reviewed. The TME was classified into four types according to the expression pattern of PD-L1 and CD8+TIL. Overall survival (OS) was assessed using the Kaplan–Meier method and Cox regression model analysis. Results: In 160 OPSCC patients, p16 was positive in 27 (16.88%). The density of CD8+ TIL was higher in the p16+ and PD-L1+ groups (p = 0.005, 0.039); however, there was no association between p16 and the status of PD-L1. P16 and CD8+ TIL were significant prognostic factors for better OS (p = 0.007, 0.001), but not PD-L1 status (p = 0.317). Among the four types of TME, carcinoma showed mainly type IV TME (PD-L1−/TIL+), while OPSCCs with type I TME (PD-L1+/TIL+) had the best survival outcome. Conclusions: The positivity of p16 and the density of CD8+ TIL were associated with better OS in OPSCC, while the status of PD-L1 was not significantly related to OS. OPSCC with type I TME (PD-L1+/TIL+) showed the best prognosis of all types of TME. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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8 pages, 702 KiB

Open AccessArticle

Novel Approach to Improving Specialist Access in Underserved Populations with Suspicious Oral Lesions

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Curr. Oncol. 2023, 30(1), 1046-1053; https://doi.org/10.3390/curroncol30010080 - 11 Jan 2023

Cited by 2 | Viewed by 1876

Abstract

Late detection and specialist referral result in poor oral cancer outcomes globally. High-risk LRMU populations usually do not have access to oral medicine specialists, a specialty of dentistry, whose expertise includes the identification, treatment, and management of oral cancers. To overcome this access barrier, there is an urgent need for novel, low-cost tele-health approaches to expand specialist access to low-resource, remote and underserved individuals. The goal of this study was to compare the diagnostic accuracy of remote versus in-person specialist visits using a novel, low-cost telehealth platform consisting of a smartphone-based, remote intraoral camera and custom software application. A total of 189 subjects with suspicious oral lesions requiring biopsy (per the standard of care) were recruited and consented. Each subject was examined, and risk factors were recorded twice: once by an on-site specialist, and again by an offsite specialist. A novel, low-cost, smartphone-based intraoral camera paired with a custom software application were utilized to perform synchronous remote video/still imaging and risk factor assessment by the off-site specialist. Biopsies were performed at a later date following specialist recommendations. The study’s results indicated that on-site specialist diagnosis showed high sensitivity (94%) and moderate specificity (72%) when compared to histological diagnosis, which did not significantly differ from the accuracy of remote specialist telediagnosis (sensitivity: 95%; specificity: 84%). These preliminary findings suggest that remote specialist visits utilizing a novel, low-cost, smartphone-based telehealth tool may improve specialist access for low-resource, remote and underserved individuals with suspicious oral lesions. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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7 pages, 927 KiB

Open AccessFeature PaperArticle

Botulinum Neurotoxin A in the Treatment of Pharyngocutaneous Fistula after Salvage Surgery in Head and Neck Cancer Patients: Our Preliminary Results

Maria Raffaella Marchese

and

Curr. Oncol. 2022, 29(10), 7099-7105; https://doi.org/10.3390/curroncol29100557 - 28 Sep 2022

Cited by 1 | Viewed by 1296

Abstract

Objective: To analyze the effect of intraparotid injection of botulinum neurotoxin A (BoNT-A) on salivary production and the course of pharyngocutaneous fistula (PCF) in post-radiation therapy salvage surgery. Methods: A total of 13 patients who had undergone total laryngectomy or pharyngolaryngectomy were treated with BoNT-A to both parotid glands, within three days from PCF onset. The salivary flow was evaluated using a subjective rating scale as the percentage of normal function from 0% (no saliva) to 100% (normal saliva flow), before injection, every day for 2 weeks, and once a week for three months. PCFs were monitored daily. Results: Spontaneous closure of PCF occurred in 7/13 (53.84%) cases 13.6 days (range: 7–18) after treatment; 6/13 (46.16%) patients needed revision surgery. Salivary flow significantly decreased in all patients seven days after injection (from 67.2% to 36.4%; p < 0.05). Patients who had undergone either conservative or surgical treatment did not differ in salivary flow before injection, whereas the mean percentages of salivary flow calculated at each time point after injection were different (p < 0.05). Conclusions: BoNT-A contributed to the closure of the fistula in most of our cases. The subjective perception of salivary flow predicted the closure of PCF. The mean time to closure may contribute to establishing the timing of PCF surgical treatment. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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11 pages, 863 KiB

Open AccessArticle

Soft Tissue Sarcomas of the Head and Neck Region with Skull Base/Intracranial Invasion: Review of Surgical Outcomes and Multimodal Treatment Strategies: A Retrospective Case Series

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Curr. Oncol. 2022, 29(9), 6540-6550; https://doi.org/10.3390/curroncol29090514 - 14 Sep 2022

Viewed by 1437

Abstract

Soft tissue sarcomas (STS) invading the skull base are rare with little data to guide surgical management. Here we aimed to determine the factors affecting tumor control rates and survival in patients with T4 stage head and neck STS involving the skull base. A retrospective review of STS patients, surgically treated at our institution between 1994 and 2017 was conducted. Variables were collected and assessed against progression-free survival. Tumors were graded using the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) system. A total of 51 patients (mean age of 35) were included, of whom 17 (33.3%) patients were FNCLCC grade 1, 8 (15. 7%) were FNCLCC grade 2 and 26 (51%) were FNCLCC grade 3. The median PFS was 236.4 months while the 5- and 10-year PFS rates were 44% and 17%, respectively. Recurrence occurred in 17 (33.3%) patients. Local recurrence occurred in 10 (58.8%). Univariate analysis revealed R0 resection had a near-significant impact on tumor control in radiation-naïve patients. Otherwise, prior radiation (HR 6.221, CI 1.236–31.314) and cavernous sinus involvement (HR 14.464, CI 3.326–62.901) were negative predictors of PFS. The most common cause of treatment failure was local recurrence. In T4 stage head and neck STS with skull-base involvement, FNCLCC grade, radiation status, and anatomic spread should be considered in determining the overall treatment strategy. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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11 pages, 1783 KiB

Open AccessArticle

Changes in Apparent Diffusion Coefficient (ADC) in Serial Weekly MRI during Radiotherapy in Patients with Head and Neck Cancer: Results from the PREDICT-HN Study

Curr. Oncol. 2022, 29(9), 6303-6313; https://doi.org/10.3390/curroncol29090495 - 31 Aug 2022

Cited by 4 | Viewed by 1685

Abstract

Background: The PREDICT-HN study aimed to systematically assess the kinetics of imaging MR biomarkers during head and neck radiotherapy. Methods: Patients with intact squamous cell carcinoma of the head and neck were enrolled. Pre-, during, and post-treatment MRI were obtained. Serial GTV and ADC measurements were recorded. The correlation between each feature and the GTV was calculated using Spearman’s correlation coefficient. The linear mixed model was used to evaluate the change in GTV over time. Results: A total of 41 patients completed the study. The majority (76%) had oropharyngeal cancer. A total of 36 patients had intact primary tumours that can be assessed on MRI, and 31 patients had nodal disease with 46 nodes assessed. Median primary GTV (GTVp) size was 14.1cc. The rate of GTVp shrinkage was highest between pre-treatment and week 4. Patients with T3-T4 tumours had a 3.8-fold decrease in GTVp compared to T1-T2 tumours. The ADC values correlated with residual GTVp. The median nodal volume (GTVn) was 12.4cc. No clinical features were found to correlate with GTVn reduction. The overall change in ADC for GTVn from pre-treatment was significant for 35th–95th percentiles in weeks 1–4 (p < 0.001). Conclusion: A discrepancy in the trajectory of ADC between primary and nodal sites suggested that they exhibit different treatment responses and should be analysed separately in future studies. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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17 pages, 2200 KiB

Open AccessArticle

Nomograms Based on Serum N-glycome for Diagnosis of Papillary Thyroid Microcarcinoma and Prediction of Lymph Node Metastasis

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Curr. Oncol. 2022, 29(9), 6018-6034; https://doi.org/10.3390/curroncol29090474 - 23 Aug 2022

Cited by 1 | Viewed by 1633

Abstract

Non-invasive biomarkers for the diagnosis and prognosis of papillary thyroid microcarcinoma (PTMC) are still urgently needed. We aimed to characterize the N-glycome of PTMC, and establish nomograms for the diagnosis of PTMC and the prediction of lymph node metastasis (LNM). N-glycome of PTMC (LNM vs. non-LNM, capsular invasion (CI) vs. non-CI (NCI)) and matched healthy controls (HC) were quantitatively analyzed based on mass spectrometry. N-glycan traits associated with PTMC/LNM were used to create binomial logistic regression models and were visualized as nomograms. We found serum N-glycome differed between PTMC and HC in high-mannose, complexity, fucosylation, and bisection, of which, four N-glycan traits (TM, CA1, CA4, and A2Fa) were significantly associated with PTMC. The nomogram based on four traits achieved good performance for the identification of PTMC. Two N-glycan traits (CA4 and A2F0S0G) showed strong associations with LNM. The nomogram based on two traits showed relatively good performance in predicting LNM. We also found differences between CI and NCI in several N-glycan traits, which were not the same as that associated with LNM. This study reported serum N-glycosylation signatures of PTMC for the first time. Nomograms constructed from aberrant glycans could be useful tools for PTMC diagnosis and stratification. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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16 pages, 1857 KiB

Open AccessArticle

The Management and Outcomes of Patients with Extra-Pulmonary Neuroendocrine Neoplasms and Brain Metastases

Zainul-Abedin Kapacee

and

Curr. Oncol. 2022, 29(7), 5110-5125; https://doi.org/10.3390/curroncol29070405 - 20 Jul 2022

Cited by 1 | Viewed by 1736

Abstract

Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP–NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP–NENs who developed BMs. Methods: A retrospective single-centre analysis of consecutive patients with EP–NENs (August 2004–February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan–Meier). Results: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15–77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP–NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease (p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5–139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery (n = 3); radiotherapy (n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months [95% CI 15.2–31.3]; median time to death from BMs diagnosis was 3.0 months [95% CI 0.0–8.3]. Conclusion: BMs in patients with EP–NENs are rare and of increased risk in G3 vs. G1 + G2 EP–NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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18 pages, 1078 KiB

Open AccessArticle

Osseous Union after Mandible Reconstruction with Fibula Free Flap Using Manually Bent Plates vs. Patient-Specific Implants: A Retrospective Analysis of 89 Patients

Michael Knitschke

Sophia Sonnabend

Fritz Christian Roller

and

Curr. Oncol. 2022, 29(5), 3375-3392; https://doi.org/10.3390/curroncol29050274 - 06 May 2022

Cited by 13 | Viewed by 3860

Abstract

The aim of this monocentric, retrospective clinical study was to evaluate the status of osseous union in uni- and poly-segmental mandible reconstructions regarding conventional angle-stable manually bent osteosynthesis plates (Unilock 2.0 mm) versus titan laser-melted PSI patient-specific implant’s (PSI). The clinical impact of PSI’s high stiffness fixation methods on bone healing and regeneration is still not well addressed. The special interest was in evaluating the ossification of junctions between mandible and fibula and between osteotomized fibula free flap (FFF) segments. Panoramic radiograph (OPT), computed tomography (CT) scans, or cone-beam CTs (CBCT) of patients who underwent successful FFF for mandible reconstruction from January 2005 to December 2020 were analyzed. A total number of 89 cases (28 females (31.5%), 61 males (68.5%), mean age 58.2 ± 11.3 years, range: 22.8–82.7 years) fulfilled the chosen inclusion criteria for analysis (conventional: n = 44 vs. PSI: n = 45). The present study found an overall incomplete ossification (IOU) rate of 24.7% (conventional: 13.6% vs. PSI: 35.6%; p = 0.017) for mandible to fibula and intersegmental junctions. Between osteotomized FFF segments, an IOU rate of 16% was found in the PSI-group, while no IOU was recorded in the conventional group (p = 0.015). Significant differences were registered for IOU rates in poly-segmental (p = 0.041), and lateral (p = 0.016) mandibular reconstructions when PSI was used. Multivariate logistic regression analysis identified plate exposure and type of plate used as independent risk factors for IOU. Previous or adjuvant radiotherapy did not impact incomplete osseous union in the evaluated study sample. PSI is more rigid than bent mini-plates and shields functional mechanical stimuli, and is the main reason for increasing the rate of incomplete ossification. To enhance the functional stimulus for ossification it has to be discussed if patient-specific implants can be designed to be thinner, and should be divided into segmental plates. This directs chewing forces through the bone and improves physiological bone remodeling. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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13 pages, 635 KiB

Open AccessArticle

Upfront DPYD Genotyping and Toxicity Associated with Fluoropyrimidine-Based Concurrent Chemoradiotherapy for Oropharyngeal Carcinomas: A Work in Progress

Phuc Felix Nguyen-Tan

Charles Vadnais

Xiaoduan Weng

and

Denis Soulières

Curr. Oncol. 2022, 29(2), 497-509; https://doi.org/10.3390/curroncol29020045 - 26 Jan 2022

Cited by 4 | Viewed by 2196

Abstract

Background: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods: The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront DPYD*2A genotyping. We aimed to determine the effect of DPYD genotyping on grade ≥3 toxicities. Results: 181 patients were analyzed (87 patients before and 94 patients following DPYD*2A screening). Of the patients, 91% (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of six additional patients with alternative DPYD variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before DPYD*2A screening versus 62% following upfront genotyping (p = 0.18). When retrospectively analyzing additional non-DPYD*2A variants, the relative risks for mucositis (RR 2.36 [1.39–2.13], p = 0.0063), dysphagia (RR 2.89 [1.20–5.11], p = 0.019), and aspiration pneumonia (RR 13 [2.42–61.5)], p = 0.00065) were all significantly increased. Conclusion: The DPYD*2A, c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can identify patients in whom 5-FU-related toxicity should be avoided. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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12 pages, 1624 KiB

Open AccessArticle

Discrimination of Cancer Stem Cell Markers ALDH1A1, BCL11B, BMI-1, and CD44 in Different Tissues of HNSCC Patients

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Curr. Oncol. 2021, 28(4), 2763-2774; https://doi.org/10.3390/curroncol28040241 - 19 Jul 2021

Cited by 9 | Viewed by 2370

Abstract

Cancer stem cells (CSCs) are accountable for the progress of head and neck squamous cell carcinoma (HNSCC). This exploratory study evaluated the expression of molecular CSC markers in different tissues of HNSCC patients. Tissue specimens of primary tumor, lymph node metastases and macroscopically healthy mucosa of 12 consecutive HNSCC patients, that were treated with surgery and adjuvant radio(chemo)therapy upon indication, were collected. Samples were assessed for the expression of p16 as a surrogate for HPV-related disease and different molecular stem cell markers (ALDH1A1, BCL11B, BMI-1, and CD44). In the cohort, seven patients had HPV-related HNSCC; six thereof were oropharyngeal squamous cell carcinoma. While expression of BMI-1 and BCL11B was significantly lower in healthy mucosa than both tumor and lymph node metastasis, there were no differences between tumor and lymph node metastasis. In the HPV-positive sub-cohort, these differences remained significant for BMI-1. However, no significant differences in these three tissues were found for ALDH1A1 and CD44. In conclusion, this exploratory study shows that CSC markers BMI-1 and BCL11B discriminate between healthy and cancerous tissue, whereas ALDH1A1 and CD44 were expressed to a comparable extent in healthy mucosa and cancerous tissues. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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Review

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14 pages, 4743 KiB

Open AccessReview

Magnetic Resonance-Guided Radiation Therapy for Head and Neck Cancers

Danny Lavigne

Sweet Ping Ng

Brian O’Sullivan

Phuc Felix Nguyen-Tan

Edith Filion

Laurent Létourneau-Guillon

Clifton D. Fuller

and

Houda Bahig

Curr. Oncol. 2022, 29(11), 8302-8315; https://doi.org/10.3390/curroncol29110655 - 31 Oct 2022

Cited by 3 | Viewed by 2116

Abstract

Despite the significant evolution of radiation therapy (RT) techniques in recent years, many patients with head and neck cancer still experience significant toxicities during and after treatments. The increased soft tissue contrast and functional sequences of magnetic resonance imaging (MRI) are particularly attractive in head and neck cancer and have led to the increasing development of magnetic resonance-guided RT (MRgRT). This approach refers to the inclusion of the additional information acquired from a diagnostic or planning MRI in radiation treatment planning, and now extends to online high-quality daily imaging generated by the recently developed MR-Linac. MRgRT holds numerous potentials, including enhanced baseline and planning evaluations, anatomical and functional treatment adaptation, potential for hypofractionation, and multiparametric assessment of response. This article offers a structured review of the current literature on these established and upcoming roles of MRI for patients with head and neck cancer undergoing RT. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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18 pages, 1890 KiB

Open AccessReview

Nasopharyngeal Carcinoma Progression: Accumulating Genomic Instability and Persistent Epstein–Barr Virus Infection

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Curr. Oncol. 2022, 29(9), 6035-6052; https://doi.org/10.3390/curroncol29090475 - 23 Aug 2022

Cited by 3 | Viewed by 2251

Abstract

Genomic instability facilitates the evolution of cells, tissues, organs, and species. The progression of human malignancies can be regarded as the accumulation of genomic instability, which confers a high evolutionary potential for tumor cells to adapt to continuous changes in the tumor microenvironment. Nasopharyngeal carcinoma (NPC) is a head-and-neck squamous-cell carcinoma closely associated with Epstein–Barr virus (EBV) infection. NPC progression is driven by a combination of accumulated genomic instability and persistent EBV infection. Here, we present a review of the key characteristics of genomic instability in NPC and the profound implications of EBV infection. We further discuss the significance of profiling genomic instability for the assessment of disease progression and treatment efficacy, as well as the opportunities and challenges of targeted therapies for NPC based on its unique genomic instability. Full article

(This article belongs to the Special Issue New Frontiers in Head and Neck Oncology)

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