Clinicopathological correlation of the immune system, cell differentiation, angiogenesis, lipid metabolism and transcriptionally active HPV in a large series of head and neck squamous cell carcinomas

• Grant number: 22/12760-9
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2023
• End date: March 31, 2025
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Jorge Esquiche León
• Grantee: Jorge Esquiche León
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated researchers: Alexandre Todorovic Fabro ; Andreia Bufalino ; Estela Kaminagakura Tango ; Fernando Chahud

Abstract

Head and neck squamous cell carcinoma (HNSCC) represents 95% of cancers in this anatomical region. Several studies evaluating the interrelationship of the immune system and cancer have demonstrated the ability of cancer cells to evade the immune response and promote a pro-tumor microenvironment. In addition to new markers of angiogenesis, proliferation and cell differentiation, recent studies show that transcription factors could efficiently determine the profile of tumor-infiltrating lymphocytes (TILs), in the context of stimulatory or inhibitory immune mechanisms (PD-1/PD-L1 axis). Cancer cells often reprogram metabolic pathways for survival, proliferation and metastasis. Although dependence on glycolysis is well studied, the role of "tumor-associated adipocytes (TAAs)" and lipid metabolic reprogramming in supporting cancer growth and proliferation, especially metastases, is less understood. Considering the human papillomavirus (HPV), several studies suggest that transcriptionally active HPV (in the HPV-driven context) is necessary to strictly associate a causal relationship of HPV in HNSCC. Thus, the present project intends to analyze through immunohistochemistry, in situ hybridization and molecular genetics a large series of HNSCC (n=500). The results will help to elucidate the immune and molecular mechanisms involved in the pathogenesis of HNSCC, in addition to providing data on lipid metabolism in tumor growth and metastasis, correlating them with the prevalence of transcriptionally active HPV and survival rates, in order to support therapeutic planning and prognosis. (AU)

Scientific publications

(25)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SILVA, EVANIO VILELA; SILVEIRA, HEITOR ALBERGONI; CANDIDO MOREIRA, THALES PERES; AUGUSTO, JEFFERSON; RAGUSA SILVA, PAULA VERONA; BUFALINO, ANDREIA; LEON, JORGE ESQUICHE. Non-Ulcerated and Ulcerated Necrotizing Sialometaplasia: Report of an Additional Case and Literature Review. INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD & NECK SURGERY, v. 75, n. 3, p. 4-pg., 2023-02-27. (18/12734-2, 16/11419-0, 17/01438-0, 22/12760-9)

SILVEIRA, HEITOR ALBERGONI; SILVA-SOUSA, YARA TERESINHA CORREA; REYES, MAGDALENA RAQUEL TORRES; BERNARDINI, VANESSA DA ROCHA; FLORIAM, LUIS JOSE; LEON, JORGE ESQUICHE. Pedunculated, papillary giant cell fibroma in a pediatric patient: An immunohistochemical and in situ hybridization study. PEDIATRIC DENTAL JOURNAL, v. 33, n. 1, p. 6-pg., 2023-03-15. (16/11419-0, 18/12734-2, 22/12760-9)

AMARAL, ELOISA COSTA; JAVARONI, JULIA BILIATO; SILVEIRA, HEITOR ALBERGONI; TRIVELLATO, ALEXANDRE ELIAS; SVERZUT, CASSIO EDVARD; LEON, JORGE ESQUICHE. Pseudocarcinomatous Squamous Hyperplasia After Surgical Management Of Pediatric Ameloblastoma: An Immunohistochemical Study. JOURNAL OF MAXILLOFACIAL & ORAL SURGERY, v. 22, n. 3, p. 5-pg., 2023-04-08. (16/11419-0, 22/12760-9)

SILVA, EVANIO VILELA; DE ANDRADE, BRUNO AUGUSTO BENEVENUTO; SILVEIRA, HEITOR ALBERGONI; ROCHA, EDUARDO MELANI; CHAHUD, FERNANDO; BRUNALDI, MARIANGELA OTTOBONI; BUFALINO, ANDREIA; LEON, JORGE ESQUICHE. Characterization of ectopic germinal centers in Sjogren's syndrome (SS) and non-SS non-sicca patients. ORAL DISEASES, v. N/A, p. 5-pg., 2023-08-11. (16/14636-2, 15/22586-2, 16/11419-0, 22/12760-9)

JAVARONI, JULIA BILIATO; SILVEIRA, HEITOR ALBERGONI; REYES, MAGDALENA RAQUEL TORRES; MESQUITA, ANA TEREZINHA MARQUES; ROCHA, GABRIELA FONSECA; LEON, JORGE ESQUICHE. Lip Granular Cell Tumor (GCT) in a Pediatric Patient: Critical Literature Review on Pediatric Intraoral GCT and Acquired and Congenital Intraoral Non-Neural GCT. INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD & NECK SURGERY, v. N/A, p. 5-pg., 2023-06-17. (16/11419-0, 22/12760-9)

SILVA, PAULA VERONA RAGUSA; PALACON, MARIANA PARAVANI; SILVEIRA, HEITOR ALBERGONI; MARTINS, KARINA HELEN; BUFALINO, ANDREIA; LEON, JORGE ESQUICHE. Oral Carcinoma Arising Under Implant-Supported Prosthesis: Progression of Proliferative Verrucous Leukoplakia Initially Mimicking Lichen Planus. JOURNAL OF ORAL IMPLANTOLOGY, v. 50, n. 4, p. 4-pg., 2024-08-01. (16/11419-0, 22/12760-9)

MARQUES, MARCELO BORGES; BARBEIRO, CAMILA OLIVEIRA; MARTINS, KARINA HELEN; POSANTES, GABRIELA ESPERANZA MARADIAGA; SILVEIRA, DEBORA FERNANDES MENDES; BUFALINO, ANDREIA; LEON, JORGE ESQUICHE. Sialadenopapillary ductal tumor: Unifying sialadenoma papilliferum-like intraductal papillary tumor and tubulopapillary hidroadenoma-like tumor of the mandible-Report of an additional case. Oral Oncology, v. 169, p. 5-pg., 2025-10-01. (16/11419-0, 22/12760-9)

MESQUITA, ANA TEREZINHA MARQUES; ROCHA, GABRIELA FONSECA; MARTINS, KARINA HELEN; BARBEIRO, CAMILA DE OLIVEIRA; SILVEIRA, HEITOR ALBERGONI; LEON, JORGE ESQUICHE. Adenomatoid Odontogenic Tumor: Histomorphological Evidence of Its Origin from the Cystic Component and Literature Review. JOURNAL OF MAXILLOFACIAL & ORAL SURGERY, v. N/A, p. 4-pg., 2025-03-14. (16/11419-0, 22/12760-9)

MARTINS, KARINA HELEN; MIRANDA-FILHO, ALUISIO EUSTAQUIO DE FREITAS; MOREIRA, THALES PERES CANDIDO; SILVEIRA, HEITOR ALBERGONI; TORRES, CAROLINA PAES; LEON, JORGE ESQUICHE. Intraoral Ulceration in a Paediatric Patient Mimicking Bednar's Aphthae. INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD & NECK SURGERY, v. N/A, p. 3-pg., 2025-06-12. (22/12760-9, 16/11419-0)

ROCHA, GABRIELA FONSECA; SILVEIRA, HEITOR ALBERGONI; SILVA, HERBERTH CAMPOS; CHAHUD, FERNANDO; BRUNALDI, MARIANGELA OTTOBONI; MARQUES MESQUITA, ANA TEREZINHA; LEON, JORGE ESQUICHE. KRT20-/SATB2+/MCPyV+ Sinonasal Merkel Cell Carcinoma: A Detailed Immunohistochemical and In Situ Hybridization Study. INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY, v. N/A, p. 6-pg., 2025-01-17. (18/12734-2, 22/12760-9)

SILVEIRA, HEITOR ALBERGONI; RAGUSA SILVA, PAULA VERONA; PIMENTEL, BRUNA GONCALVES; NOGUEIRA, GUSTAVO MILHOMENS; CHAHUD, FERNANDO; BRUNALDI, MARIANGELA OTTOBONI; LEON, JORGE ESQUICHE. Lymphomatoid Papulosis "Type E" Affecting the Palate: A Detailed Case Report and Review of Literature. AMERICAN JOURNAL OF DERMATOPATHOLOGY, v. 45, n. 5, p. 4-pg., 2023-05-01. (18/12734-2, 16/11419-0, 22/12760-9)

REYES, MAGDALENA RAQUEL; LOPES DOMINGUETE, MATHEUS HENRIQUE; JAVARONI, JULIA BILIATO; DA SILVEIRA, HEITOR ALBERGONI; SILVA, EVANIO VILELA; LEON, JORGE ESQUICHE. Lingual Actinomycosis Clinically Simulating Nodular Median Rhomboid Glossitis: Literature Review and Report of Additional Case. INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD & NECK SURGERY, v. N/A, p. 4-pg., 2023-06-30. (16/11419-0, 22/12760-9)

SILVEIRA, HEITOR ALBERGONI; JAVARONI, JULIA BILIATO; FERREIRA DA SILVA, ANDERSON TANGERINO; TORRES REYES, MAGDALENA RAQUEL; HASHIMOTO, JENNIFER MAYUMI; CUADRA-ZELAYA, FLORENCE JUANA MARIA; LOPES DOMINGUETE, MATHEUS HENRIQUE; MARQUES MESQUITA, ANA TEREZINHA; BRUNALDI, MARIANGELA OTTOBONI; BUFALINO, ANDREIA; et al. Lipometaplasia in fibrous hyperplasia and inflammatory fibrous hyperplasia of the oral cavity. JOURNAL OF CUTANEOUS PATHOLOGY, v. N/A, p. 6-pg., 2023-07-02. (16/11419-0, 22/12760-9)

PALACON, MARIANA PARAVANI; MARQUES, MARCELO BORGES; SILVEIRA, DEBORA FERNANDES MENDES; MARTINS, KARINA HELEN; SILVEIRA, HEITOR ALBERGONI; PEREIRA-FILHO, VALFRIDO ANTONIO; BUFALINO, ANDREIA; CHAHUD, FERNANDO; LEON, JORGE ESQUICHE. Intraoral Lymphomatoid Papulosis Type D Showing Scarce/Absent CD30 Expression in A Pediatric Patient: Case Report and Literature Review. Head and Neck Pathology, v. 19, n. 1, p. 5-pg., 2025-02-05. (16/11419-0, 22/12760-9)

MARQUES, MARCELO BORGES; POSANTES, GABRIELA ESPERANZA MARADIAGA; GONCALVES, LUANA STEFANIE SILVINO; DA SILVA, ANDERSON TANGERINO FERREIRA; SILVEIRA, HEITOR ALBERGONI; CHAHUD, FERNANDO; LEON, JORGE ESQUICHE. Multifocal Necrotizing Sialometaplasia in the Tongue Surgical Specimen: An Immunohistochemical Study. Head and Neck Pathology, v. 19, n. 1, p. 4-pg., 2025-02-05. (16/11419-0, 22/12760-9)

FORERO, BRENDA CAROLINA PATTIGNO; REYES, MAGDALENA RAQUEL TORRES; POSANTES, GABRIELA ESPERANZA MARADIAGA; DE ALMEIDA, ISABELLA VICTORIA; MARTINS, KARINA HELEN; BUFALINO, ANDREIA; LEON, JORGE ESQUICHE. Intraoral Foreign Body-Type Giant Cell Reaction in a Sjögren's Syndrome Patient: An Immunohistochemical Analysis. JOURNAL OF MAXILLOFACIAL & ORAL SURGERY, v. N/A, p. 5-pg., 2024-11-13. (16/11419-0, 22/12760-9)

SILVA, EVANIO VILELA; DOMINGUETE, MATHEUS HENRIQUE LOPES; MARTINS, KARINA HELEN; REYES, MAGDALENA RAQUEL TORRES; SILVEIRA, HEITOR ALBERGONI; DA SILVA, ANDERSON TANGERINO FERREIRA; LEON, JORGE ESQUICHE. Intraoral epithelioid and spindle cell hemangioma associated with pseudoepitheliomatous hyperplasia: An immunohistochemical study. JOURNAL OF CUTANEOUS PATHOLOGY, v. 51, n. 2, p. 5-pg., 2023-11-02. (16/11419-0, 22/12760-9)

DA COSTA, ADRIANA APARECIDA SILVA; OLIVEIRA, SICILIA REZENDE; TAVARES, THALITA SOARES; MEIRELLES, DANIELA PEREIRA; DA SILVA, EVANIO VILELA; DA SILVA, ANDERSON TANGERINO FERREIRA; LEON, JORGE ESQUICHE; CARDOSO, SERGIO VITORINO; DE AGUIAR, MARIA CASSIA FERREIRA; DA SILVA, TARCILIA APARECIDA; et al. Contribution of HPV Status for Neutrophil Extracellular Traps Release in Oropharyngeal Cancer. JOURNAL OF ORAL PATHOLOGY & MEDICINE, v. N/A, p. 8-pg., 2024-11-24. (22/12760-9)

BARBEIRO, CAMILA OLIVEIRA; SILVEIRA, HEITOR ALBERGONI; BARBEIRO, ROBERTO HENRIQUE; MARTINS, KARINA HELEN; BUFALINO, ANDREIA; CHAHUD, FERNANDO; LEON, JORGE ESQUICHE. Intraoral CD30+T-Cell Lymphoproliferative Disorder with Lymphomatoid Papulosis Type C Features Mimics Lymphoma Histopathologically and Immunohistochemically. Head and Neck Pathology, v. 18, n. 1, p. 4-pg., 2024-06-28. (16/11419-0, 22/12760-9)

GONCALVES, LUANA STEFANIE SILVINO; MARTINS, KARINA HELEN; REYES, MAGDALENA RAQUEL TORRES; CATANANTI, ISABELLA SILVA; CHAHUD, FERNANDO; LEON, JORGE ESQUICHE. Light-chain-restricted Russell body oral mucositis: an immunohistochemical study and literature review. Leukemia & Lymphoma, v. 65, n. 8, p. 4-pg., 2024-04-15. (16/11419-0, 22/12760-9)

REYES, MAGDALENA RAQUEL TORRES; JAVARONI, JULIA BILIATO; NOGUEIRA, GUSTAVO MILHOMENS; ZELAYA, FLORENCE JUANA MARIA CUADRA; DE LEON, ANYELI SORAYA ALAS; SILVEIRA, HEITOR ALBERGONI; LEON, JORGE ESQUICHE. Resolution of blood eosinophilia and limited mouth opening after short-term follow-up in a pediatric Langerhans cell histiocytosis case. INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD & NECK SURGERY, v. 75, n. 3, p. 4-pg., 2023-05-02. (16/11419-0, 22/12760-9)

SILVEIRA, HEITOR ALBERGONI; SILVA, ANDREIA APARECIDA; DIAS, RAFAEL RODRIGUES; MARTINS, KARINA HELEN; DA SILVA, ANDERSON TANGERINO FERREIRA; CARDOSO, CAMILA LOPES; LEON, JORGE ESQUICHE. Maxillary Mesenchymal Chondrosarcoma Affecting A Pediatric Patient: Case Report Showing Long-Term Follow-Up and Detailed Literature Review. JOURNAL OF MAXILLOFACIAL & ORAL SURGERY, v. N/A, p. 5-pg., 2025-02-09. (18/12734-2, 16/11419-0, 22/12760-9)

SILVEIRA, HEITOR ALBERGONI; MARTINS, KARINA HELEN; ANBINDER, ANA LIA; SANTOS, THAIS AGUIAR; BARROS, ELTON FERNANDES; ALVES, POLLIANNA MUNIZ; NONAKA, CASSIANO FRANCISCO WEEGE; MESQUITA, ANA TEREZINHA MARQUES; DOMINGUETE, MATHEUS HENRIQUE LOPES; DIAS, RAFAEL RODRIGUES; et al. Histopathological variants of head and neck squamous cell carcinomas: A multicenter study in Latin America. ANNALS OF DIAGNOSTIC PATHOLOGY, v. 80, p. 17-pg., 2026-02-01. (16/11419-0, 18/12734-2, 22/12760-9)

DA COSTA, ADRIANA APARECIDA SILVA; GUIEIRO, RAFAEL SOARES; DE OLIVEIRA, INGRID GOMES; TAVARES, THALITA SOARES; MEIRELLES, DANIELA PEREIRA; DA SILVA, EVANIO VILELA; DA SILVA, ANDERSON TANGERINO FERREIRA; LEON, JORGE ESQUICHE; DE AGUIAR, MARIA CASSIA FERREIRA; CALDEIRA, PATRICIA CARLOS. HPV-related oropharyngeal carcinoma remains infrequent over 25 years in a Brazilian Oral Pathology Center: A cross-sectional study with literature review. MEDICINA ORAL PATOLOGIA ORAL Y CIRUGIA BUCAL, v. 29, n. 4, p. 11-pg., 2024-07-01. (22/12760-9)

REYES, MAGDALENA RAQUEL TORRES; MARTINS, KARINA HELEN; POSANTES, GABRIELA ESPERANZA MARADIAGA; ZELAYA, FLORENCE JUANA MARIA CUADRA; RENDEROS, SANDRA GUADALUPE GONGORA; LEON, JORGE ESQUICHE. Myofibroma with Atypical Features can Mimic Low-Grade Myofibroblastic Sarcoma: Two Paediatric Cases. INDIAN JOURNAL OF OTOLARYNGOLOGY AND HEAD & NECK SURGERY, v. N/A, p. 4-pg., 2024-06-25. (16/11419-0, 22/12760-9)