Altered immune responses in HR-HPV infected women

Abstract

Persistent infection with high-risk human papillomavirus (HR-HPV) is the primary cause of cervical cancer (CC). However, most HPV infections are transient and are cleared by effective host immune responses. Therefore, understanding the mechanisms that allow viral persistence and immune escape is critical to explaining why only a subset of women develops cervical lesions and invasive cancer. Although cervical cancer is largely preventable through vaccination and screening, it remains a major cause of cancer-related morbidity and mortality among women worldwide, with a disproportionate burden in low- and middle-income countries. This significant disparity underscores the ongoing inequities in access to HPV vaccination, screening, and timely treatment, which hinder the World Health Organization aim to eliminate cervical cancer as a public health concern by 2030. This narrative review examines how viral, host, and microenvironmental factors interact to promote HR-HPV persistence and cervical cancer development, with particular attention to evidence from Mexican women. HR-HPV can evade immune surveillance by interfering with innate immune recognition, interferon signaling, antigen presentation, and cytotoxic lymphocyte activity. These alterations are compounded by cervicovaginal dysbiosis, immunosuppressive cytokines, regulatory-cell expansion, host genetic variation, and altered microRNA expression. Together, these interconnected processes impair viral clearance and create conditions that favor the progression of cervical lesions to invasive cancer. A comprehensive understanding of these mechanisms may facilitate the identification of biomarkers of HPV persistence and disease progression, while supporting the development of more effective immunotherapeutic strategies and precision prevention approaches, particularly for populations disproportionately affected by cervical cancer.