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ISSN 打印: 0893-9675
ISSN 在线: 2162-6448


DOI: 10.1615/CritRevOncog.2020033071
pages 403-413

Role of Epstein-Barr Virus and Human Papillomavirus Coinfection in Oral and Anogenital Carcinogenesis: Potential Tumorigenic Pathways

Marcos Antonio Pereira de Lima
School of Medicine, Federal University of Cariri, UFCA, Barbalha, Ceará, Brazil
Ilara Parente Pinheiro Teodoro
School of Medicine, Federal University of Cariri, UFCA, Barbalha, Ceará, Brazil
Cláudio Gleidiston Lima da Silva
School of Medicine, Federal University of Cariri, UFCA, Barbalha, Ceará, Brazil
Marcos Venício Alves Lima
Ceará Cancer Institute, ICC, Fortaleza, Ceará, Brazil


Epstein-Barr virus (EBV) and human papillomavirus (HPV) have been implicated in 38% of all virus-related cancers. Over the past three decades, both have been detected in anogenital and head-and-neck squamous cell carcinomas (HNSCC), with evidence of involvement in tumor genesis and progression. Very little has been published on HPV/EBV coinfection. In this chapter, we review the literature on the role of these viruses in oral carcinoma and draw parallels with other HNSCCs and anogenital carcinomas, with emphasis on their interplay and potential signaling pathways. EBV infection seems to create an environment that favors HPV latency, supporting the claim that EBV is a cofactor in HPV-related carcinomas. In turn, under certain circumstances, HPV appears to be able to induce EBV to switch to the latent or replicative state. The main viral oncogenes expressed in these malignancies are EBNA1, EBNA2, LMP1, EBERs, and the high-risk HPV oncogenes E6 and E7. The most well-documented human proteins involved are p53, pRb, p16INK4a, p19ARF, Myc, E-cadherin, β-catenin, EGFR, MLH1, and COX-2. These proteins are directly associated not only with viral products but also with one another in the development of malignancy. Knowledge of the molecular machinery behind carcinomas coinfected with HPV and EBV may help understand how these viruses trigger carcinogenesis and subsidize the development of new biomarkers of tumor aggressiveness and prognosis, alternative surrogate virus markers, and possible therapeutic targets.


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