Relationships between lymphomas linked to hepatitis C virus infection and their microenvironment

Table 1 Biological agents assessed by the International Agency for Research on Cancer Monographs Working Group[9]

Group-1 agent	Cancers on which sufficient evidence in humans is based	Other sites with limited evidence in humans	Established mechanistic events
Epstein–Barr virus	Nasopharyngeal carcinoma, Burkitt lymphoma, Immune-suppression-related non-Hodgkin lymphoma, Extranodal NK/T-cell lymphoma (nasal type), Hodgkin lymphoma	Gastric carcinoma1 Lympho-epithelioma-like carcinoma1	Cell proliferation, inhibition of apoptosis, genomic instability, cell migration
Hepatitis B virus	Hepatocellular carcinoma	Cholangiocarcinoma1, Non-Hodgkin lymphoma1	Inflammation, liver cirrhosis, chronic hepatitis2
Hepatitis C virus	Hepatocellular carcinoma, Non-Hodgkin lymphoma1	Cholangiocarcinoma1	Inflammation, liver cirrhosis, liver fibrosis
Kaposi sarcoma herpes virus	Kaposi sarcoma1, Primary effusion lymphoma1	Multicentric Castleman’s disease1	Cell proliferation, inhibition of apoptosis, genomic instability, cell migration
Human immunodeficiency virus, type 1	Kaposi sarcoma, Non-Hodgkin lymphoma, Hodgkin lymphoma1, Cancer of the cervix1, anus1, conjunctiva1	Cancer of the vulva1, vagina1, penis1, Non-melanoma skin cancer1, Hepatocellular carcinoma1	Immunosuppression (indirect action)
Human papillomavirus type 16 (For the other types see Table 2)	Carcinoma of the cervix, vulva, vagina, penis, anus, oral cavity, oropharynx and tonsil	Cancer of the larynx	Immortalization, genomic instability, inhibition of DNA damage response, anti-apoptotic activity
Helicobacter pylori	Non-cardia gastric carcinoma, Low-grade B-cell mucosa-associated lymphoid tissue gastric lymphoma1		Inflammation, oxidative stress, altered cellular turnover, changes in gene expression, methylation, mutation

¹Newly identified link between virus and cancer. In red are highlighted the lymphoid proliferations;

²HBV has both a direct and indirect role in promoting hepatocellular carcinoma. Modified and adapted from Bouvard et al[8].

Table 2 Hepatitis C virus-associated indolent and aggressive lymphoid proliferations

Subtype	Variant	Specific lymphoma sites
Monoclonal B-cell lymphocytosis
Tissue based monoclonal B cell and plasma cell proliferations of uncertain type
Lymphoplasmocytic lymphoma/WM
Chronic lymphocytic disorders (non CLL)
MZL	Splenic MZL
	Nodal MZL
	MALT	Gastric
		Extranodal non gastric
		Salivary gland
		Skin
		Orbit
		Liver
Diffuse large B-cell lymphoma

WM: Waldenström’s macroglobulinemia; CLL: Chronic lymphocytic leukemia; MZL: Marginal zone lymphoma; MALT: Mucosa-associated lymphoid tissue.