Lesões epiteliais benignas e malignas da orofaringe: aspectos demográficos, detecção do Papilomavírus Humano (HPV) e avaliação da resposta imune

Abstract

This study aimed to evaluate the frequency, clinicopathological characteristics, and HPV status of oropharyngeal squamous cell carcinoma (OP-SCC) and benign epithelial lesions related to HPV, diagnosed at the Oral Pathology Service, School of Dentistry, of Universidade Federal de Minas Gerais. Additionally, a literature review was performed to investigate HPV frequency in OP-SCC samples diagnosed in Brazilian Centers. The study also aimed to identify and compare the presence of neutrophils and neutrophil extracellular traps (NETs) in HPV-positive and HPV negative OPSCC cases, and to quantify neutrophils, B-lymphocytes, and T lymphocytes in these cases, as well as in oropharyngeal squamous papillomas. Cases diagnosed between 1997 and 2021 with histopathological diagnoses of squamous papilloma, condyloma accuminatum, verruca vulgaris, and OP-SCC, were included. Clinicopathological data were collected, and HPV status in OPSCCs was assessed using immunohistochemistry and in situ hybridization. Bivariate statistical analysis was performed. In the second step, OPSCC biopsy specimens were submitted to immunohistochemistry for CD66b to detect neutrophils and immunofluorescence to identify NETs through colocalization of myeloperoxidase (MPO) and citrullinated histone H3 (H3Cit). In the final step, immunohistochemistry was used to identify neutrophils (CD66b), B-lymphocytes (CD20), cytotoxic T lymphocytes (CD8), and helper T lymphocytes (CD4) in HPV-positive and HPV-negative OPSCC cases, as well as squamous papillomas. 211 OPSCC (63.0%) and 124 benign lesions (37.0%) were analyzed. The frequency of OPSCC increased over time, while HPV-positive carcinomas remained infrequent, and benign lesions had steady trends. OPSCC affected more males (81.0%), although the relative frequency in females rose over time. Smoking (60.2%) was common in OPSCC, and nineteen OP-SCC (13.0%) were positive for HPV. HPV-positive and HPV-negative tumors exhibited similar clinicopathological features (p>0.05). Benign lesions predominated in middle-aged (26.7%) women (57.3%), in the soft palate (81.5%). The literature review included 32 studies; in 60%, HPV frequency in OP-SCC was less than 25%. HPV-positive and HPV-negative OPSCCs showed similar neutrophil infiltration (p>0.05), but NET release was higher in HPV-positive tumors (p<0.05). NET expression did not affect overall survival (p>0.05). Benign lesions had a lower infiltration of CD66b+ and CD20+ cells than malignant lesions (p<0.05). CD8+ and CD4+ cells did not differ significantly among the groups (p>0.05). In HPV-positive OPSCC, CD4+ T cells outnumbered the other cell subtypes analyzed (p<0.05). In HPV-negative OPSCC, a significant difference was observed only between CD4+ and CD20+ cells (p<0.001). Benign lesions expressed higher levels of CD4+ and CD8+ cells than CD20+ and CD66b+ cells (p<0.05). Overall survival was not associated with CD66b, CD20, CD8, or CD4 indexes (p>0.05). OP-SCC prevalence has been increasing, and it was mostly associated with smoking and alcohol rather than with HPV infection in Brazil. Benign lesions had a stationary frequency. HPV may stimulate NET release in the OP-SCC microenvironment. Malignant lesions demonstrated higher infiltration of CD66b and CD20 than benign lesions. A pronounced T-cell response was observed in both malignant and benign epithelial lesions of the oropharynx.