The Role of Sex Hormone Receptors in the Squamous Cell Carcinoma of the Uterine Ectocervix: A Review and Future Directions.

Cervical cancer (CxCa) remains a major global gynecological malignancy causally linked to high-risk human papillomavirus (HPV) infection. However, HPV alone is insufficient for carcinogenesis; sex hormones and their receptors serve as essential cofactors. This review aims to synthesize current knowledge on the role of cervical histoarchitecture and hormonal microenvironments in ectocervical squamous cell carcinoma (SCC), and to explore how receptor-mediated signals contribute to malignant transformation and metastatic spread. The review examines the expression patterns of estrogen receptor α (ERα) and progesterone receptor (PR) in the uterine cervix, which is a hormone-responsive tissue. It discusses how these receptors fluctuate throughout the menstrual cycle and evaluates evidence from HPV-transgenic mouse models and human tissue analyses. The findings converge on a compelling model: stromal ERα drives pro-carcinogenic paracrine signaling, epithelial PR suppresses neoplastic transformation, and stromal PRB confers antimetastatic protection. These insights highlight the complex interplay between hormonal signals and SCC development in the ectocervix. Future therapeutic exploitation of these mechanistic insights-including selective estrogen receptor modulators, selective progesterone receptor modulators, and PR status-guided chemoprevention-holds considerable promise. This review provides a coherent framework for translating laboratory findings into clinical diagnostics and targeted interventions.