Abstract

Viruses are pathogenic agents responsible for approximately 10% of all human cancers and significantly contribute to the global cancer burden. Until now, eight viruses have been associated with the development of a broad range of malignancies, including solid and haematological tumours. Besides triggering and promoting oncogenesis, viral infections often go hand-in-hand with haemostatic changes, representing a potential risk factor for venous thromboembolism (VTE). Conversely, VTE is a cardiovascular condition that is particularly common among oncological patients, with a detrimental impact on patient prognosis. Despite an association between viral infections and coagulopathies, it is unclear whether viral-driven tumours have a different incidence and prognosis pattern of thromboembolism compared to non-viral-induced tumours. Thus, this review aims to analyse the existing evidence concerning the association of viruses and viral tumours with the occurrence of VTE. Except for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection, which are associated with a high risk of VTE, little evidence exists concerning the thrombogenic potential associated with oncoviruses. As for tumours that can be induced by oncoviruses, four levels of VTE risk are observed, with hepatocellular carcinoma (HCC) and gastric carcinoma (GC) associated with the highest risk and nasopharyngeal carcinoma (NPC) associated with the lowest risk. Unfortunately, the incidence of cancer-related VTE according to tumour aetiology is unknown. Given the negative impact of VTE in oncological patients, research is required to better understand the mechanisms underlying blood hypercoagulability in viral-driven tumours to improve VTE management and prognosis assessment in patients diagnosed with these tumours.

Conclusion

Viruses are well-known pathogenic agents responsible for the direct and indirect development of approximately 10% of human cancers. Several viruses linked to oncogenesis in humans have been identified, including HBV, HCV, EBV, HPV, KSHV, HTLV-1, HIV and MCPyV, which are associated with a vast diversity of malignant diseases. Beyond tumorigenesis, viruses are major inducers of blood coagulability. Indeed, haemostasis is frequently disturbed by the pro-inflammatory environment imposed by viral infections, which supports the idea that a viral infection can trigger thromboembolic events.

Conversely, over the years, the association between cancer and thrombosis has been a matter of discussion among researchers. This cardiovascular disease is commonly diagnosed in patients with malignancy and constitutes their second cause of death after cancer. Indeed, there is a bidirectional and complex interplay between both conditions, with tumour cells interacting with haemostatic components and, in parallel, promoting cancer progression and aggressiveness, which worsens the patients’ clinical outcomes.

Although seemingly evident, the literature has not discussed venous thrombosis in viral-induced tumours. Since cancer patients may harbour the oncovirus for their whole life (e.g., chronic infections), and given the remarkably complex interplay of viral infections with both cancer development and haemostasis, it would be of interest to identify a potential pattern of VTE incidence across viral-driven tumours, as well as the putative underlying mechanisms. Except for HCV and HIV, which are associated with an increased VTE risk with several underlying mechanisms proposed, most viruses (HBV, EBV, HPV, HTLV-1 and KSHV) have only a putative associated VTE risk, and few to no mechanisms currently described. On the other hand, for MCPyV, no association was found. Conversely, among the various tumours that can be induced by oncoviruses, GC and HCC were associated with the highest VTE risk, HL, NHL and CC were included in the intermediate VTE risk, while NPC was included in the lowest VTE risk category. Furthermore, to the best of our knowledge, data regarding KS, ATL and MCC association with venous thrombosis was not available in the literature, therefore, considered unknown. Unfortunately, whether the incidence of thrombosis in cancer patients is influenced by tumour aetiology is unexplored, at least to the best of our knowledge, and it is unclear to what extent the presence of viral infections in oncological patients can induce thrombogenesis, being further studies required to fulfil the current gaps in our knowledge.

Overall, the present review summarized the data concerning VTE risk and the associated mechanisms across several viral-induced tumours. This is relevant given the need to better predict VTE development, allowing for better thromboprophylaxis and ultimately improving the prognosis of patients diagnosed with these tumours. Furthermore, the data exposed can be useful to identify potential therapeutic targets that could improve VTE treatment efficacy and decrease the associated side effects, the major one being haemorrhage, which is more common among oncological patients. Beyond the influence of tumour aetiology on thrombosis development, another point to be explored is whether thromboembolic events may facilitate viral infection, reinfection, and viral carcinogenesis.