Expression of hypoxia-inducible factor 1-alpha in diverse histological types of uterine cervical carcinoma and correlation with the aggressiveness of tumor type: An immunohistochemical study

Background: Cervical cancer is the fourth leading cause of cancer-related deaths in women worldwide, with high prevalence in South Africa. High-risk human papillomavirus (HPV), along with genetic and epigenetic alterations, drives cervical carcinogenesis. Hypoxia-inducible factor 1-alpha (HIF-1alpha) is frequently expressed in cervical carcinoma and other solid tumors. Under normoxia, HIF-1alpha is degraded via the Von Hippel-Lindau pathway, while hypoxia stabilizes it, inducing angiogenic factors. HIF-1alpha immunohistochemistry has been proposed as a prognostic and therapeutic marker; however, previous studies are limited by small cohorts, single-center designs, and variable histology. This study assessed HIF-1alpha expression across cervical carcinoma subtypes and its association with tumor aggressiveness. Methods: We conducted a retrospective study of cervical carcinoma cases diagnosed at the University of Pretoria (2017-2022). Archived formalin-fixed paraffin-embedded tissues were retrieved, yielding 63 cases. HIF-1alpha immunohistochemistry was performed, and three pathologists independently scored staining using a modified quick Allred system, classifying cases as positive if the combined score exceeded zero. Results: HIF-1alpha expression was positive in 19/63 cases (30%) and negative in 44/63 (70%). Basaloid squamous cell carcinoma accounted for 26% of positive cases, CIN III-like and papillary squamous-urothelial carcinomas each 21%, adenoid basal, papillary squamous, and clear cell carcinomas 10% each, and adenosquamous carcinoma 5%. No adenoid cystic, small cell, or villoglandular carcinomas were positive. Positivity within subtypes was highest in papillary squamous-urothelial (57%) and clear cell (50%) carcinomas, followed by basaloid squamous cell (38%), adenoid basal (33%), CIN III-like and papillary squamous cell (28.5%), and adenosquamous (25%). Conclusion: HIF-1alpha is expressed in a subset of cervical carcinomas, predominantly in histological variants associated with aggressive behavior, suggesting a potential link with poorer prognosis. Limited sample size and single-center design warrant caution. Larger multicenter studies with clinical follow-up are needed to clarify whether HIF-1alpha can guide prognostic assessment or targeted therapy in cervical carcinoma.