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Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the...
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Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the Alimentary Tract

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

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 38041

Special Issue Editors

Mr. Francesco Cavallin

E-Mail Website
Guest Editor
Independent Statistician, Solagna, Italy
Interests: medical statistics; systematic review and meta-analysis; esophageal cancer; colorectal cancer; melanoma; surgical oncology
Dr. Marco Scarpa

E-Mail Website
Guest Editor
Azienda Ospedaliera di Padova, Padova, Italy
Interests: surgical oncology; esophageal cancer; colorectal cancer; systematic review and meta-analysis; cancer immunology; inflammatory bowel disease; colorectal surgery; upper GI surgery

Special Issue Information

Dear Colleagues,

Squamous cell carcinomas of the alimentary tract (head and neck; esophagus; anal canal) are aggressive malignancies with poor prognosis. A better understanding of the mechanisms of carcinogenesis can identify areas of preventive interventions. Head and neck squamous cell carcinoma and esophageal squamous cell carcinoma are associated with elevated mutational load but lacks specific genetic mutations, while anal cancer is very often associated with human papillomavirus. Several evidences suggest a crucial role of the immune system in eradicating such neoplasms. Moreover, checkpoint inhibitors were shown to improve survival in advanced squamous cell carcinomas.

In the future years, we expect an establishment of precision medicine modalities to extend survival and improve quality of life of patients with these neoplasms. Considering such prospective, policy makers and stakeholders can benefit from summarizing efforts aiming at highlighting the most effective approaches and promoting areas of further research.

In this Special Issue of Cancers, we invite systematic reviews to address such challenges for squamous cell carcinomas of the alimentary tract. Topics will include but are not limited to pathogenesis of these cancers; mechanisms of carcinogenesis; immunosurveillance; detection strategies; role of biomarkers; tumor spreading; identification of novel therapeutic targets. This Special Issue aims to highlight the current state in pathogenesis, detection and spread of squamous cell carcinomas of the alimentary tract, and to identify gaps of knowledge.

Mr. Francesco Cavallin
Dr. Marco Scarpa
Guest Editors

Manuscript Submission Information

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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.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • squamous cell carcinoma
  • esophagus
  • head/neck
  • anal canal
  • immunology
  • oncology
  • pathogenesis
  • immune surveillance
  • HPV
  • HIV
  • immune suppression

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Published Papers (6 papers)

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Review

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24 pages, 1486 KiB  
Review
ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers
by Albina Fejza, Lucrezia Camicia, Evelina Poletto, Greta Carobolante, Maurizio Mongiat and Eva Andreuzzi
Cancers 2021, 13(11), 2759; https://doi.org/10.3390/cancers13112759 - 2 Jun 2021
Cited by 7 | Viewed by 5714
Abstract
Squamous cell carcinomas (SCC) include a number of different types of tumors developing in the skin, in hollow organs, as well as the upper aerodigestive tract (UADT) including the head and neck region and the esophagus which will be dealt with in this [...] Read more.
Squamous cell carcinomas (SCC) include a number of different types of tumors developing in the skin, in hollow organs, as well as the upper aerodigestive tract (UADT) including the head and neck region and the esophagus which will be dealt with in this review. These tumors are often refractory to current therapeutic approaches with poor patient outcome. The most important prognostic determinant of SCC tumors is the presence of distant metastasis, significantly correlating with low patient survival rates. Rapidly emerging evidence indicate that the extracellular matrix (ECM) composition and remodeling profoundly affect SSC metastatic dissemination. In this review, we will summarize the current knowledge on the role of ECM and its remodeling enzymes in affecting the growth and dissemination of UADT SCC. Taken together, these published evidence suggest that a thorough analysis of the ECM composition in the UADT SCC microenvironment may help disclosing the mechanism of resistance to the treatments and help defining possible targets for clinical intervention. Full article
(This article belongs to the Special Issue Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the Alimentary Tract)
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31 pages, 1018 KiB  
Review
Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma
by Florencia Veigas, Yamil D. Mahmoud, Joaquin Merlo, Adriana Rinflerch, Gabriel Adrian Rabinovich and María Romina Girotti
Cancers 2021, 13(5), 1018; https://doi.org/10.3390/cancers13051018 - 1 Mar 2021
Cited by 28 | Viewed by 5021
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors usually diagnosed at an advanced stage and characterized by a poor prognosis. The main risk factors associated with its development include tobacco and alcohol consumption and Human Papillomavirus (HPV) infections. [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of tumors usually diagnosed at an advanced stage and characterized by a poor prognosis. The main risk factors associated with its development include tobacco and alcohol consumption and Human Papillomavirus (HPV) infections. The immune system has a significant role in the oncogenesis and evolution of this cancer type. Notably, the immunosuppressive tumor microenvironment triggers immune escape through several mechanisms. The improved understanding of the antitumor immune response in solid tumors and the role of the immune checkpoint molecules and other immune regulators have led to the development of novel therapeutic strategies that revolutionized the clinical management of HNSCC. However, the limited overall response rate to immunotherapy urges identifying predictive biomarkers of response and resistance to treatment. Here, we review the role of the immune system and immune checkpoint pathways in HNSCC, the most relevant clinical findings linked to immunotherapeutic strategies and predictive biomarkers of response and future treatment perspectives. Full article
(This article belongs to the Special Issue Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the Alimentary Tract)
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13 pages, 753 KiB  
Review
Risk Factors of Esophageal Squamous Cell Carcinoma beyond Alcohol and Smoking
by Munir Tarazi, Swathikan Chidambaram and Sheraz R. Markar
Cancers 2021, 13(5), 1009; https://doi.org/10.3390/cancers13051009 - 28 Feb 2021
Cited by 35 | Viewed by 4933
Abstract
Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of death worldwide. Incidence rates vary internationally, with the highest rates found in Southern and Eastern Africa, and central Asia. Initial observational studies identified multiple factors associated with an increased risk of [...] Read more.
Esophageal squamous cell carcinoma (ESCC) is the sixth most common cause of death worldwide. Incidence rates vary internationally, with the highest rates found in Southern and Eastern Africa, and central Asia. Initial observational studies identified multiple factors associated with an increased risk of ESCC, with subsequent work then focused on developing plausible biological mechanistic associations. The aim of this review is to summarize the role of risk factors in the development of ESCC and propose future directions for further research. A systematic search of the literature was conducted by screening EMBASE, MEDLINE/PubMed, and CENTRAL for relevant publications. In total, 73 studies were included that sought to identify risk factors associated with the development of esophageal squamous cell carcinoma. Risk factors were divided into seven subcategories: genetic, dietary and nutrition, gastric atrophy, infection and microbiome, metabolic, epidemiological and environmental and other risk factors. Risk factors from each subcategory were summarized and explored with mechanistic explanations for these associations. This review highlights several current risk factors of ESCC. These risk factors were explored, and explanations dissected. Most studies focused on investigating genetic and dietary and nutritional factors, whereas this review identified other potential risk factors that have yet to be fully explored. Furthermore, there is a lack of literature on the association of these risk factors with tumor factors and disease prognosis. Further research to validate these results and their effects on tumor biology is absolutely necessary. Full article
(This article belongs to the Special Issue Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the Alimentary Tract)
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19 pages, 2478 KiB  
Review
The Pathologic and Molecular Landscape of Esophageal Squamous Cell Carcinogenesis
by Gianluca Businello, Paola Parente, Luca Mastracci, Gianmaria Pennelli, Giulia Traverso, Massimo Milione, Elena Bellan, Mauro Michelotto, Andromachi Kotsafti, Federica Grillo and Matteo Fassan
Cancers 2020, 12(8), 2160; https://doi.org/10.3390/cancers12082160 - 4 Aug 2020
Cited by 27 | Viewed by 5673
Abstract
Esophageal squamous cell carcinoma represents the most common histotype of epithelial neoplasm occurring within esophageal mucosa worldwide. Despite the comprehensive molecular characterization of this entity, to date no significant targeted therapy has been introduced into clinical practice. In this review, we describe the [...] Read more.
Esophageal squamous cell carcinoma represents the most common histotype of epithelial neoplasm occurring within esophageal mucosa worldwide. Despite the comprehensive molecular characterization of this entity, to date no significant targeted therapy has been introduced into clinical practice. In this review, we describe the molecular landscape of esophageal squamous cell carcinoma based on the most recent literature. Moreover, we focus on other rare variants and on the relationship with head and neck squamous cell carcinomas. Full article
(This article belongs to the Special Issue Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the Alimentary Tract)
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18 pages, 959 KiB  
Review
Distribution of Lymph Node Metastases in Esophageal Carcinoma Patients Undergoing Upfront Surgery: A Systematic Review
by Eliza R. C. Hagens, Mark I. van Berge Henegouwen and Suzanne S. Gisbertz
Cancers 2020, 12(6), 1592; https://doi.org/10.3390/cancers12061592 - 16 Jun 2020
Cited by 45 | Viewed by 10946
Abstract
Metastatic lymphatic mapping in esophageal cancer is important to determine the optimal extent of the radiation field in case of neoadjuvant chemoradiotherapy and lymphadenectomy when esophagectomy is indicated. The objective of this review is to identify the distribution pattern of metastatic lymphatic spread [...] Read more.
Metastatic lymphatic mapping in esophageal cancer is important to determine the optimal extent of the radiation field in case of neoadjuvant chemoradiotherapy and lymphadenectomy when esophagectomy is indicated. The objective of this review is to identify the distribution pattern of metastatic lymphatic spread in relation to histology, tumor location, and T-stage in patients with esophageal cancer. Embase and Medline databases were searched by two independent researchers. Studies were included if published before July 2019 and if a transthoracic esophagectomy with a complete 2- or 3-field lymphadenectomy was performed without neoadjuvant therapy. The prevalence of lymph node metastases was described per histologic subtype and primary tumor location. Fourteen studies were included in this review with a total of 8952 patients. We found that both squamous cell carcinoma and adenocarcinoma metastasize to cervical, thoracic, and abdominal lymph node stations, regardless of the primary tumor location. In patients with an upper, middle, and lower thoracic squamous cell carcinoma, the lymph nodes along the right recurrent nerve are often affected (34%, 24% and 10%, respectively). Few studies describe the metastatic pattern of adenocarcinoma. The current literature is heterogeneous in the classification and reporting of lymph node metastases. This complicates evidence-based strategies in neoadjuvant and surgical treatment. Full article
(This article belongs to the Special Issue Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the Alimentary Tract)
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11 pages, 945 KiB  
Systematic Review
Fistula-Related Cancer in Crohn’s Disease: A Systematic Review
by Andromachi Kotsafti, Melania Scarpa, Imerio Angriman, Ignazio Castagliuolo and Antonino Caruso
Cancers 2021, 13(6), 1445; https://doi.org/10.3390/cancers13061445 - 22 Mar 2021
Cited by 23 | Viewed by 4716
Abstract
Perianal fistulizing Crohn’s disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn’s disease are also at risk of perianal fistula-related squamous cell carcinoma (SCC). Cancer arising at the site of a chronic perianal fistula is rare [...] Read more.
Perianal fistulizing Crohn’s disease is a very disabling condition with poor quality of life. Patients with perianal fistulizing Crohn’s disease are also at risk of perianal fistula-related squamous cell carcinoma (SCC). Cancer arising at the site of a chronic perianal fistula is rare in patients with Crohn’s disease and there is a paucity of data regarding its incidence, diagnosis and management. A systematic review of the literature was undertaken using Medline, Embase, Pubmed, Cochrane and Web of Science. Several small series have described sporadic cases with perianal cancer in Crohn’s disease. The incidence rate of SCC related to perianal fistula was very low (<1%). Prognosis was poor. Colorectal disease, chronic perianal disease and HPV infection were possible risk factors. Fistula-related carcinoma in CD (Chron’s disease) can be very difficult to diagnose. Examination may be limited by pain, strictures and induration of the perianal tissues. HPV is an important risk factor with a particular carcinogenesis mechanism. MRI can help clinicians in diagnosis. Examination under anesthesia is highly recommended when findings, a change in symptoms, or simply long-standing disease in the perineum are present. Future studies are needed to understand the role of HPV vaccination in preventing fistula-related cancer. Full article
(This article belongs to the Special Issue Pathogenesis, Detection and Spread of Squamous Cell Carcinoma in the Alimentary Tract)
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