The immune microenvironment of HPV-associated cancers: from viral oncogenesis to immunotherapy response

Human papillomavirus (HPV) is a DNA virus with oncogenic potential. Persistent infections with high-risk HPV genotypes can drive malignant transformation in multiple tissues, resulting in distinct HPV-associated cancers. This review provides an analysis of the tumor microenvironment (TME) in head and neck squamous cell carcinoma (HNSCC) and squamous cell carcinoma of uterine cervix (CESC). First, we briefly introduce the key aspects of HPV biology and the mechanisms of carcinogenesis. We focus on the composition and functional states of immune cells within tumor tissues, highlighting how specific immune cells influence disease progression and clinical outcomes. By linking immunological features to patient prognosis, we outline the similarities and differences between the TME of HNSCC and CESC. Additionally, this review summarizes the current standards of care and emerging therapeutic strategies for patients with HPV-associated tumors. Altogether, by providing recent advances in the understanding of the TME of HPV-associated tumors, this review highlights the potential of targeting immune components within the tumor microenvironment for therapeutic benefit.