Every year at least 1.3 million of newly diagnosed cancers, accounting for 12% of all diagnosis worldwide, are a direct consequence of different oncogenic viral infections. These chronic viral infections and viral-associated malignancies are present in all geographic locations but are more prevalent in developing countries. However, their prevalence in developed countries is increasing due to multiple factors including iatrogenic immunosuppression, HIV infection, changes in sexual practices and immigration patterns.

Even though oncogenic viruses are genetically diverse ‐ with both RNA and DNA viruses being able to establish malignancies ‐ they all share a common characteristic - their ability to establish lifelong chronic infections. Seven different viruses have confirmed oncogenic abilities: 1) Hepatitis B and 2) Hepatitis C viruses (HBV / HCV), 3) Human T‐Lymphotropic Virus (HTLV‐1), 4) Human Papillomaviruses (HPV), 5) Karposi’s Sarcoma‐Associated Herpesvirus (KSHV), 6) Merkel Cell Polyomavirus (MCPyV) and 7) Epstein‐Barr Virus (EBV). In addition, CMV has been associated with certain carcinomas while HIV, despite not being oncogenic per se , allows for a tumor permissive environment through immunosuppression.

Despite the critical role of T cells in controlling viral replication, persistent infection reflects the failure of the immune system to control the infection. This enables oncogenic viruses to evade immune recognition and to induce transformation and proliferation of infected cells. Immune‐based therapies focused on restoring the exhausted immune system to clear infected or transformed cells are currently being developed as powerful tools for both chronic viral infections and cancer. Checkpoint inhibitor blockade, adoptive cell transfer and antibody-drug conjugates are among the most successful immunotherapies targeting the adaptive immune system. Other strategies aim to increase the innate immune response by modulating TLR receptors, blocking specific cytokines or enhancing NK cell activity. In the particular case of oncogenic viral infections, immunotherapies are of particular interest, since they can be developed and utilized in both preventative and curative settings.

By acting early, preventing, and/or treating oncogenic viral infections, cancer incidence would decrease by 19% in developing countries and by 3.8% in developed countries. Preventive vaccines are an important immunotherapeutic strategy to protect from viral-associated malignancies. However, even when preventive vaccines are available (such as the HPV vaccine), complete eradication is unlikely due to the lack of availability, or due to non-compliance with vaccination. Immunotherapeutic strategies can be then directed towards curing the viral infection before malignancy is established. However, if prevention of initial infection or early curative treatment fails, immune‐based therapies can be still directed to treat the cancer driven by these oncogenic viruses. In this case, and in addition to all the immune-oncology strategies currently under consideration, the presence of the instigating viral infection could have therapeutic implications. It has been well documented that virus-specific lymphocytes, anti-HPV lymphocytes in head and neck cancer lesions or anti-EBV lymphocytes in nasopharyngeal carcinoma, are detected among tumor infiltrating lymphocytes (TILs), suggesting that restoring anti-viral immunity could also be a helpful strategy against viral-associated malignancies.

The aim of this Research Topic is to provide a comprehensive overview of the latest research focused on immunotherapy for oncogenic viral infections as prophylaxis, infectious diseases and/or cancer treatment. We seek Original Research articles, Reviews, Mini‐Reviews, Methods, Protocols and Perspective articles that address, but are not limited to, the following topics:

1. Immunotherapy to prevent oncogenic viral infection.
2. Immunotherapy for oncogenic viral infections: innate immune system.
3. Immunotherapy for oncogenic viral infections: adaptive immune system.
4. Immunotherapy for virus‐associated malignancies: innate immune system.
5. Immunotherapy for virus‐associated malignancies: adaptive immune system.

We particularly welcome submissions on the following viral pathogens: CMV, EBV, HBV, HCV, HIV, HPV, HTLV-1, KSHV and MCPyV.

Dr. Sara Ferrando Martinez and Dr. Scott Robbins are currently employed at Medimmune LLC, a member of the AstraZeneca Group, Gaithersburg, MD, USA.

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