Immunohistochemical assessment of proliferation, angiogenesis, and viral markers in recurrent laryngeal papillomatosis

Abstract

Recurrent laryngeal papillomatosis (RLP) is a benign but clinically aggressive condition, characterized by frequent recurrences and significant morbidity. Although infection with the human papillomavirus (HPV) represents the main etiological factor, the biological mechanisms underlying the persistence and recurrence of lesions remain incompletely understood. This study aimed to perform a comprehensive histopathological and immunohistochemical evaluation of recurrent laryngeal papillomatosis, focusing on epithelial proliferat ion, angiogenesis, the inflammatory microenvironment, and HPV expression. A retrospective tissue-based study was conducted on a cohort of 32 surgically excised laryngeal papilloma specimens obtained from adult patients. Conventional histopathological examination was performed using hematoxylin–eosin staining. Immunohistochemical analysis included HPV markers, Ki-67, VEGF-A, CD31, and CD68. Proliferative activity, angiogenesis, and inflammatory infiltrates were assessed using semi-quantitat ive and quantitative methods. Statistical analysis was performed using standard comparative tests, with a p-value < 0.05 considered statistically significant. Histopathological evaluation revealed a typical papillary architecture, with fibrovascular stromal cores, epithelial acanthosis, koilocytic changes, and chronic inflammatory infiltrates. HPV immunopositivity was detected in 21.9% of cases, predominantly in the suprabasal epithelial layers, displaying a mosaic pattern. All lesions showed positivity for Ki-67, with heterogeneous proliferative indices. CD68-positive macrophages were variably distributed within the subepithelial stroma. CD31 immunostaining demonstrated a dense and mature microvascular network in all cases. VEGF-A expression was present in the majority of lesions and showed a moderate positive correlation with microvascular density, indicating active angiogenesis. Recurrent laryngeal papillomatosis is characterized by a complex interaction between epithelial proliferation, angiogenesis, chronic inflammation, and HPV-associated changes. VEGF-A-mediated angiogenesis appears to play a significant role in sustaining lesion growth. Comprehensive immunohistochemical profiling provides valuable insights into the biological behavior of RLP and may contribute to improved risk stratification and the development of targeted therapeutic strategies.