Euclides Avila

Vasculogenic mimicry in human cancers associated with chronic high-risk human papillomavirus infection

Vasculogenic mimicry (VM) allows tumor cells to form vessel-like channels, promoting growth, metastasis, and therapy resistance. Persistent infection with high-risk human papillomavirus (HPV), mainly types 16 and 18, is a key factor in various cancers, including anogenital and head and neck cancers. VM has been documented in cervical cancer and oral squamous cell carcinoma (OSCC), but its role in other HPV-associated cancers remains unexplored. This review summarizes literature published between October 2024 and April 2025 in PubMed and Google Scholar, focusing on VM in HPV-related cancers. General mechanisms highlighted include epithelial-mesenchymal transition, hypoxia, and activation of STAT3 and PI3K/AKT pathways. Molecular regulators include TXNDC5, CHI3L1, erythropoietin, and microRNAs miR-124 and miR-29b in cervical cancer; and collagen XVI, LGR5, ALDH1, Beclin 1, VE-cadherin, CD44, HIF-1α, and SOX7 in OSCC. From a translational perspective, elucidating the molecular regulators of VM could reveal therapeutic opportunities through strategies targeting specific signaling pathways in tumor cells.

The Interaction of Human Papillomavirus Infection and Prostaglandin E2 Signaling in Carcinogenesis: A Focus on Cervical Cancer Therapeutics

Chronic infection by high-risk human papillomaviruses (HPV) and chronic inflammation are factors associated with the onset and progression of several neoplasias, including cervical cancer. Oncogenic proteins E5, E6, and E7 from HPV are the main drivers of cervical carcinogenesis. In the present article, we review the general mechanisms of HPV-driven cervical carcinogenesis, as well as the involvement of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and downstream effectors in this pathology. We also review the evidence on the crosstalk between chronic HPV infection and PGE2 signaling, leading to immune response weakening and cervical cancer development. Finally, the last section updates the current therapeutic and preventive options targeting PGE2-derived inflammation and HPV infection in cervical cancer. These treatments include nonsteroidal anti-inflammatory drugs, prophylactic and therapeutical vaccines, immunomodulators, antivirals, and nanotechnology. Inflammatory signaling pathways are closely related to the carcinogenic nature of the virus, highlighting inflammation as a co-factor for HPV-dependent carcinogenesis. Therefore, blocking inflammatory signaling pathways, modulating immune response against HPV, and targeting the virus represent excellent options for anti-tumoral therapies in cervical cancer.

The Preventive Role of the Vitamin D Endocrine System in Cervical Cancer

Vitamin D along with its active metabolite calcitriol and its metabolic and signaling system, known as the vitamin D endocrine system, have been widely recognized as a pivotal regulator of calcium homeostasis in addition to non-calcemic antitumoral effects in a variety of human cancers, including cervical cancer. Several studies have found an inverse relationship between the incidence of cervical neoplasia and vitamin D levels. This narrative review updates the current evidence supporting the notion that the vitamin D endocrine system has a preventive role on cervical cancer, mainly in the early phases of the disease, acting at the level of suppressing cell proliferation, promoting apoptosis, modulating inflammatory responses, and probably favoring the clearance of human papillomavirus-dependent cervical lesions. Although an optimal vitamin D status helps in the prevention and regression of low-grade squamous intraepithelial lesions of the cervix, it appears that vitamin D alone or combined with chemotherapeutic agents has little effectivity once advanced cervical cancer is established. These observations suggest that an optimal vitamin D status might exert beneficial actions in the early phases of cervical cancer by preventing its onset and progression.