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Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches

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A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Clinical Research of Cancer".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 42540

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Special Issue Editors

Prof. Dr. Robert Mandic

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Guest Editor

Department of Otolaryngology, Head and Neck Surgery, University Hospital Giessen and Marburg, Campus Marburg, Baldingerstrasse, D-35033 Marburg, Germany
Interests: head and neck cancer; HNSCC; therapy resistance; p53; EGFR; tumor virus; HPV; CRPV; rabbit VX2 carcinoma

Prof. Dr. Boris A. Stuck

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Guest Editor

Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Marburg, Philipps-Universität Marburg, 35033 Marburg, Germany
Interests: Head and Neck Squamous Cell Carcinoma; Clinical Guidelines; Clinical Trials of Cancer

Special Issue Information

Dear Colleagues,

Decisions aiming for the best treatment of head and neck cancer (HNC) patients have to be made during everyday clinical practice. These therapeutic decisions are typically tailored to the specific situation of the single HNC patient. Therapy choice is highly dependent on the patient’s tumor stage but also has to consider other factors such as the patient’s age and morbidity. To offer a patient the best possible therapy option, interdisciplinary decision making is required, involving disciplines such as otorhinolaryngology and head and neck surgery, oral and maxillofacial surgery, radiation oncology, pathology, and internal medicine. Over the past years, new disciplines, such as molecular pathology, as the basis for precision medicine, are becoming more and more prevalent owing to the fact that gaining information about tumor genomes can have a major impact on therapeutic choices particularly in patients which have no other treatment options. To address this complex situation, this Special Issue focuses on aspects that influence the choice of therapy for HNC patients. For this, it is of utmost importance to bring together opinions and expertise from clinically and basic-research focused disciplines.

We therefore would like to invite and encourage you to contribute an article (original or review) to your area of expertise in the field of HNC and discuss how you think this could impact HNC therapeutic decision making.

With kind regards,

Prof. Dr. Robert Mandic
Prof. Dr. Boris A. Stuck
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

HNSCC
head and neck cancer
therapy decision
therapeutic tumor models
precision medicine

Published Papers (13 papers)

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15 pages, 1767 KiB

Open AccessArticle

Bayesian Networks to Support Decision-Making for Immune-Checkpoint Blockade in Recurrent/Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC)

by Marius Huehn, Jan Gaebel, Alexander Oeser, Andreas Dietz, Thomas Neumuth, Gunnar Wichmann and Matthaeus Stoehr

Cancers 2021, 13(23), 5890; https://doi.org/10.3390/cancers13235890 - 23 Nov 2021

Cited by 3 | Viewed by 1667

Abstract

New diagnostic methods and novel therapeutic agents spawn additional and heterogeneous information, leading to an increasingly complex decision-making process for optimal treatment of cancer. A great amount of information is collected in organ-specific multidisciplinary tumor boards (MDTBs). By considering the patient’s tumor properties, molecular pathological test results, and comorbidities, the MDTB has to consent an evidence-based treatment decision. Immunotherapies are increasingly important in today’s cancer treatment, resulting in detailed information that influences the decision-making process. Clinical decision support systems can facilitate a better understanding via processing of multiple datasets of oncological cases and molecular genetic information, potentially fostering transparency and comprehensibility of available information, eventually leading to an optimum treatment decision for the individual patient. We constructed a digital patient model based on Bayesian networks to combine the relevant patient-specific and molecular data with depended probabilities derived from pertinent studies and clinical guidelines to calculate treatment decisions in head and neck squamous cell carcinoma (HNSCC). In a validation analysis, the model can provide guidance within the growing subject of immunotherapy in HNSCC and, based on its ability to calculate reliable probabilities, facilitates estimation of suitable therapy options. We compared actual treatment decisions of 25 patients with the calculated recommendations of our model and found significant concordance (Cohen’s κ = 0.505, p = 0.009) and 84% accuracy. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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12 pages, 897 KiB

Open AccessArticle

Upfront Surgery vs. Primary Chemoradiation in an Unselected, Bicentric Patient Cohort with Oropharyngeal Squamous Cell Carcinoma—A Matched-Pair Analysis

by Philipp H. Zimmermann, Marijn Stuut, Nora Wuerdemann, Kathrin Möllenhoff, Malte Suchan, Hans Eckel, Philipp Wolber, Shachi J. Sharma, Fabian Kämmerer, Christine Langer, Claus Wittekindt, Steffen Wagner, Bernd Kremer, Ernst Jan M. Speel and Jens P. Klussmann

Cancers 2021, 13(21), 5265; https://doi.org/10.3390/cancers13215265 - 20 Oct 2021

Cited by 3 | Viewed by 1462

Abstract

The two pillars of therapy for oropharyngeal squamous cell carcinoma (OPSCC) are upfront surgery and primary chemoradiotherapy. Substantial regional preferences exist with regard to the selection of treatment. Despite new therapeutic approaches, patient survival remains poor, with an approximate overall survival (OS) rate of 50% at five years. This study was conducted to investigate a potential survival benefit depending on the treatment modality in OPSCC patients. We retrospectively collected data of 853 patients with histologically confirmed OPSCC from the Giessen and Maastricht cancer databases. To identify risk factors affecting survival, a Cox-proportional hazard model was applied to 442 patients with complete data sets. Based on this cohort a matched-pair analysis with 158 patients was performed to compare OS rates of patients treated either with upfront surgery or primary chemoradiation. For the collective cohort, patients treated with upfront surgery had significantly improved OS rates compared to patients treated with primary chemoradiation. In the matched-pair analysis adjusted for patients’ T-, N- and HPV-status as well as risk profile, we observed that both treatment approaches offered equivalent OS rates. Our study emphasizes that treatment recommendations should be made whenever possible on the basis of side-effect profiles caused by the therapeutic approach used. To draw further conclusions, results of the ongoing “best of” (NCT2984410) study are eagerly awaited, investigating the functional outcome after treatment of OPSCC patients. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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22 pages, 6372 KiB

Open AccessArticle

Prognostic Gene Signature for Squamous Cell Carcinoma with a Higher Risk for Treatment Failure and Accelerated MEK-ERK Pathway Activity

by Bohai Feng, Kai Wang, Esther Herpel, Michaela Plath, Wilko Weichert, Kolja Freier, Karim Zaoui and Jochen Hess

Cancers 2021, 13(20), 5182; https://doi.org/10.3390/cancers13205182 - 15 Oct 2021

Cited by 5 | Viewed by 2194

Abstract

Squamous cell carcinoma (SCC) is the most prevalent histological type of human cancer, including head and neck squamous cell carcinoma (HNSCC). However, reliable prognostic gene signatures for SCC and underlying genetic and/or epigenetic principles are still unclear. We identified 37 prognostic candidate genes by best cutoff computation based on survival in a pan-SCC cohort (n = 1334) of The Cancer Genome Atlas (TCGA), whose expression stratified not only the pan-SCC cohort but also independent HNSCC validation cohorts into three distinct prognostic subgroups. The most relevant prognostic genes were prioritized by a Least Absolute Shrinkage and Selection Operator Cox regression model and were used to identify subgroups with high or low risks for unfavorable survival. An integrative analysis of multi-omics data identified FN1, SEMA3A, CDH2, FBN1, COL5A1, and ADAM12 as key nodes in a regulatory network related to the prognostic phenotype. An in-silico drug screen predicted two MEK inhibitors (Trametinib and Selumetinib) as effective compounds for high-risk SCC based on the Cancer Cell Line Encyclopedia, which is supported by a higher p-MEK1/2 immunohistochemical staining of high-risk HNSCC. In conclusion, our data identified a molecular classifier for high-risk HNSCC as well as other SCC patients, who might benefit from treatment with MEK inhibitors. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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15 pages, 3408 KiB

Open AccessArticle

Human Adipose-Derived Stem/Stromal Cells Promote Proliferation and Migration in Head and Neck Cancer Cells

by Kariem Sharaf, Tanja K. Eggersmann, Stefan P. Haider, Sabina Schwenk-Zieger, Jiefu Zhou, Olivier Gires, Axel Lechner, Martin Canis and Frank Haubner

Cancers 2021, 13(11), 2751; https://doi.org/10.3390/cancers13112751 - 1 Jun 2021

Cited by 10 | Viewed by 2720

Abstract

Human adipose-derived stem/stromal cells (ASCs) are increasingly used as auto-transplants in regenerative medicine to restore tissue defects or induce wound healing, especially in cancer patients. The impact of ASCs on squamous cell carcinoma of the upper aerodigestive tract (UAT) including head and neck and esophageal squamous cell carcinoma (HNSCC and ESCC) is not yet fully understood. ASCs were cultured from subcutaneous, abdominal lipoaspirates of five patients, who received auto-transplants to the head and neck. Supernatants were tested for paracrine effects in functional in vitro assays of proliferation of HNSCC tumor cell line FaDu and ESCC cell line Kyse30, and their cell migration/invasion capacities in Boyden chambers, in addition to endothelial tube formation assay using human umbilical vein endothelial cells (HUVECs). All ASC-derived supernatants enhanced proliferation of FaDu cells, invasive migration, and tube formation by HUVECs, compared to controls. Of five patients’ lipoaspirates, ASC-derived supernatants of four patients increased proliferation and invasive migration in Kyse30 cells. The data suggests that ASCs can promote tumor cell proliferation, invasiveness, and neo-angiogenesis in these tumor cell lines of the UAT and HUVEC in a paracrine manner. Although clinical studies on the subject of oncological safety are still needed, these findings emphasize the importance of complete tumor removal before ASCs are used in the head and neck. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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16 pages, 1403 KiB

Open AccessArticle

Impact of Tumor Site and Adjuvant Radiotherapy on Survival of Patients with Adenoid Cystic Carcinoma: A SEER Database Analysis

by Jason Tasoulas, Kimon Divaris, Stamatios Theocharis, Douglas Farquhar, Colette Shen, Trevor Hackman and Antonio L. Amelio

Cancers 2021, 13(4), 589; https://doi.org/10.3390/cancers13040589 - 3 Feb 2021

Cited by 13 | Viewed by 2812

Abstract

Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor, displaying aggressive behavior with frequent recurrence and metastasis. Little information exists regarding the impact of clinicopathological parameters and adjuvant radiotherapy (aRT) on ACC disease specific (DSS) and overall survival (OS). We extracted demographic, treatment, and survival information of 1439 patients with major or minor intraoral salivary gland ACC from the Surveillance, Epidemiology, and End Results (SEER) database. The associations between tumor characteristics and aRT with OS and DSS were estimated using hazard ratios (HR) and 95% confidence intervals (CI). Submandibular gland ACCs had the worst prognosis (adjusted DSS HR = 1.48; 95% CI = 0.99–2.20, compared to parotid), and this difference was more pronounced among patients with advanced-stage tumors (adjusted DSS HR = 1.93; 95% CI = 1.13–3.30). aRT was associated with increased overall survival only among stage III submandibular ACC patients (HR = 0.64; 95% CI = 0.42–0.98) and had no benefit in any other group. In conclusion, submandibular gland ACC carries a worse prognosis than other gland subsites and may benefit from aRT. The different outcomes between submandibular gland and other major or minor gland ACCs warrant further mechanistic investigation. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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Review

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16 pages, 1027 KiB

Open AccessReview

Malignant Vascular Tumors of the Head and Neck—Which Type of Therapy Works Best?

by Susanne Wiegand, Andreas Dietz and Gunnar Wichmann

Cancers 2021, 13(24), 6201; https://doi.org/10.3390/cancers13246201 - 9 Dec 2021

Cited by 6 | Viewed by 3106

Abstract

Malignant vascular tumors of the head and neck are rare neoplasms with variable clinical presentation, wide age distribution, and variable clinical courses. The heterogeneous presentation of angiosarcomas and epithelioid hemangioendothelioma often leads to misdiagnosis and unsuitable treatment. While risk factors for angiosarcomas are previous radiation, chronic lymphedema, and exposure to arsenic, thorium oxide, or vinyl chloride, there are only limited and retrospective data available on prognostic factors in EHE. In both angiosarcomas and EHE, surgery is the mainstay of treatment. There is limited evidence regarding the role of radiotherapy in EHE, although EHE is considered relatively radiosensitive. In angiosarcomas, adjuvant radiotherapy is recommended according to retrospective case series. A standard medical therapy for metastasized malignant vascular tumors is lacking. Chemotherapy, which is effective in angiosarcoma, is mostly ineffective in EHE. Targeted therapy, antiangiogenetic drugs and immunotherapy have been studied as new treatment options. The goal of this review is to summarize the current data regarding malignant vascular tumors along with their diagnosis and management. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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13 pages, 2126 KiB

Open AccessReview

New Scenarios in Pharmacological Treatments of Head and Neck Squamous Cell Carcinomas

by Cristina Porcheri and Thimios A. Mitsiadis

Cancers 2021, 13(21), 5515; https://doi.org/10.3390/cancers13215515 - 3 Nov 2021

Cited by 11 | Viewed by 3172

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent types of cancer with a lethal outcome in half of the diagnosed cases. Mostly, HNSCC develops in the oral cavity, and its development is associated with tobacco and areca nut/betel quid usage, alcohol consumption, and HPV infection. Oral squamous cell carcinoma, as other head and neck cancers, presents a high degree of intratumor heterogeneity, which makes their treatment difficult, and directly correlates with drug resistance. Since the classical treatments for HNSCC oftentimes do not resolve the clinical picture, there is great need for novel therapeutic approaches, models for drug testing, and new drug delivery systems. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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32 pages, 482 KiB

Open AccessReview

Current and Emerging Molecular Therapies for Head and Neck Squamous Cell Carcinoma

by Farzaneh Kordbacheh and Camile S. Farah

Cancers 2021, 13(21), 5471; https://doi.org/10.3390/cancers13215471 - 30 Oct 2021

Cited by 20 | Viewed by 2965

Abstract

Head and neck cancer affects nearly 750,000 patients, with more than 300,000 deaths annually. Advances in first line surgical treatment have improved survival rates marginally particularly in developed countries, however survival rates for aggressive locally advanced head and neck cancer are still poor. Recurrent and metastatic disease remains a significant problem for patients and the health system. As our knowledge of the genomic landscape of the head and neck cancers continues to expand, there are promising developments occurring in molecular therapies available for advanced or recalcitrant disease. The concept of precision medicine is underpinned by our ability to accurately sequence tumour samples to best understand individual patient genomic variations and to tailor targeted therapy for them based on such molecular profiling. Not only is their purported response to therapy a factor of their genomic variation, but so is their inclusion in biomarker-driven personalised medicine therapeutic trials. With the ever-expanding number of molecular druggable targets explored through advances in next generation sequencing, the number of clinical trials assessing these targets has significantly increased over recent years. Although some trials are focussed on first-line therapeutic approaches, a greater majority are focussed on locally advanced, recurrent or metastatic disease. Similarly, although single agent monotherapy has been found effective in some cases, it is the combination of drugs targeting different signalling pathways that seem to be more beneficial to patients. This paper outlines current and emerging molecular therapies for head and neck cancer, and updates readers on outcomes of the most pertinent clinical trials in this area while also summarising ongoing efforts to bring more molecular therapies into clinical practice. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

22 pages, 2937 KiB

Open AccessFeature PaperReview

Epithelial-to-Mesenchymal Transition-Derived Heterogeneity in Head and Neck Squamous Cell Carcinomas

by Philipp Baumeister, Jiefu Zhou, Martin Canis and Olivier Gires

Cancers 2021, 13(21), 5355; https://doi.org/10.3390/cancers13215355 - 26 Oct 2021

Cited by 17 | Viewed by 3605

Abstract

Head and neck squamous cell carcinomas (HNSCC) are common tumors with a poor overall prognosis. Poor survival is resulting from limited response to multi-modal therapy, high incidence of metastasis, and local recurrence. Treatment includes surgery, radio(chemo)therapy, and targeted therapy specific for EGFR and immune checkpoint inhibition. The understanding of the molecular basis for the poor outcome of HNSCC was improved using multi-OMICs approaches, which revealed a strong degree of inter- and intratumor heterogeneity (ITH) at the level of DNA mutations, transcriptome, and (phospho)proteome. Single-cell RNA-sequencing (scRNA-seq) identified RNA-expression signatures related to cell cycle, cell stress, hypoxia, epithelial differentiation, and a partial epithelial-to-mesenchymal transition (pEMT). The latter signature was correlated to nodal involvement and adverse clinical features. Mechanistically, shifts towards a mesenchymal phenotype equips tumor cells with migratory and invasive capacities and with an enhanced resistance to standard therapy. Hence, gradual variations of EMT as observed in HNSCC represent a potent driver of tumor progression that could open new paths to improve the stratification of patients and to innovate approaches to break therapy resistance. These aspects of molecular heterogeneity will be discussed in the present review. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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26 pages, 1880 KiB

Open AccessReview

Targeted Treatment of Head and Neck (Pre)Cancer: Preclinical Target Identification and Development of Novel Therapeutic Applications

by Anne M. van Harten and Ruud H. Brakenhoff

Cancers 2021, 13(11), 2774; https://doi.org/10.3390/cancers13112774 - 3 Jun 2021

Cited by 11 | Viewed by 6262

Abstract

Head and neck squamous cell carcinomas (HNSCC) develop in the mucosal lining of the upper-aerodigestive tract. In carcinogen-induced HNSCC, tumors emerge from premalignant mucosal changes characterized by tumor-associated genetic alterations, also coined as ‘fields’ that are occasionally visible as leukoplakia or erythroplakia lesions but are mostly invisible. Consequently, HNSCC is generally diagnosed de novo at more advanced stages in about 70% of new diagnosis. Despite intense multimodality treatment protocols, the overall 5-years survival rate is 50–60% for patients with advanced stage of disease and seems to have reached a plateau. Of notable concern is the lack of further improvement in prognosis despite advances in treatment. This can be attributed to the late clinical presentation, failure of advanced HNSCC to respond to treatment, the deficit of effective targeted therapies to eradicate tumors and precancerous changes, and the lack of suitable markers for screening and personalized therapy. The molecular landscape of head and neck cancer has been elucidated in great detail, but the absence of oncogenic mutations hampers the identification of druggable targets for therapy to improve outcome of HNSCC. Currently, functional genomic approaches are being explored to identify potential therapeutic targets. Identification and validation of essential genes for both HNSCC and oral premalignancies, accompanied with biomarkers for therapy response, are being investigated. Attentive diagnosis and targeted therapy of the preceding oral premalignant (preHNSCC) changes may prevent the development of tumors. As classic oncogene addiction through activating mutations is not a realistic concept for treatment of HNSCC, synthetic lethality and collateral lethality need to be exploited, next to immune therapies. In recent studies it was shown that cell cycle regulation and DNA damage response pathways become significantly altered in HNSCC causing replication stress, which is an avenue that deserves further exploitation as an HNSCC vulnerability for treatment. The focus of this review is to summarize the current literature on the preclinical identification of potential druggable targets for therapy of (pre)HNSCC, emerging from the variety of gene knockdown and knockout strategies, and the testing of targeted inhibitors. We will conclude with a future perspective on targeted therapy of HNSCC and premalignant changes. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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17 pages, 302 KiB

Open AccessReview

De-Escalation Strategies of (Chemo)Radiation for Head-and-Neck Squamous Cell Cancers—HPV and Beyond

by Alexander Rühle, Anca-Ligia Grosu and Nils H. Nicolay

Cancers 2021, 13(9), 2204; https://doi.org/10.3390/cancers13092204 - 4 May 2021

Cited by 23 | Viewed by 2879

Abstract

Oncological outcomes for head-and-neck squamous cell carcinoma (HNSCC) patients are still unsatisfactory, especially for advanced tumor stages. Besides the moderate survival rates, the prevalence of severe treatment-induced normal tissue toxicities is high after multimodal cancer treatments, both causing significant morbidity and decreasing quality of life of surviving patients. Therefore, risk-adapted and individualized treatment approaches are urgently needed for HNSCC patients to optimize the therapeutic gain. It has been a well-known fact that especially HPV-positive oropharyngeal squamous cell carcinoma (OSCC) patients exhibit an excellent prognosis and may therefore be subject to overtreatment, resulting in long-term treatment-related toxicities. Regarding the superior prognosis of HPV-positive OSCC patients, treatment de-escalation strategies are currently investigated in several clinical trials, and HPV-positive OSCC may potentially serve as a model for treatment de-escalation also for other types of HNSCC. We performed a literature search for both published and ongoing clinical trials and critically discussed the presented concepts and results. Radiotherapy dose or volume reduction, omission or modification of concomitant chemotherapy, and usage of induction chemotherapy are common treatment de-escalation strategies that are pursued in clinical trials for biologically selected subgroups of HNSCC patients. While promising data have been reported from various Phase II trials, evidence from Phase III de-escalation trials is either lacking or has failed to demonstrate comparable outcomes for de-escalated treatments. Therefore, further data and a refinement of biological HNSCC stratification are required before deescalated radiation treatments can be recommended outside of clinical trials. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

17 pages, 2648 KiB

Open AccessReview

Total Laryngectomy—Still Cutting-Edge?

by Thomas K. Hoffmann

Cancers 2021, 13(6), 1405; https://doi.org/10.3390/cancers13061405 - 19 Mar 2021

Cited by 14 | Viewed by 4460

Abstract

Surgical removal of the larynx (total laryngectomy) offers a curative approach to patients with advanced laryngeal and hypopharyngeal (squamous cell) cancer without distant metastases. Particularly in T4a carcinoma, laryngectomy seems prognostically superior to primary radio(chemo)therapy. Further relevant indications for laryngectomy include massive laryngeal dysfunction associated with aspiration and recurrence after radio(chemo)therapy, resulting in salvage surgery. The surgical procedure including neck dissection is highly standardised and safe. The resulting aphonia can be compensated by functional rehabilitation (e.g., voice prosthesis) associated with a significant quality of life improvement. This article presents an overview of indications, preoperative diagnostics, surgical procedures, including new developments (robotics), possible complications, the choice of adjuvant treatment, alternative therapeutic approaches, rehabilitation and prognosis. In summary, total laryngectomy still represents a relevant surgical procedure in modern head and neck oncology. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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Other

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15 pages, 1290 KiB

Open AccessSystematic Review

Prognostic Significance of CD4+ and CD8+ Tumor-Infiltrating Lymphocytes in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis

by Daniele Borsetto, Michele Tomasoni, Karl Payne, Jerry Polesel, Alberto Deganello, Paolo Bossi, James R. Tysome, Liam Masterson, Giancarlo Tirelli, Margherita Tofanelli and Paolo Boscolo-Rizzo

Cancers 2021, 13(4), 781; https://doi.org/10.3390/cancers13040781 - 13 Feb 2021

Cited by 63 | Viewed by 3114

Abstract

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. Full article

(This article belongs to the Special Issue Head and Neck Cancer – the Rationale behind Different Therapeutic Approaches)

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