Table 1.

Carcinogenesis mechanism and prevention/treatment strategies for infection-associated cancers.

Pathogen	Type of Cancer	Carcinogenesis Mechanism	Prevention/Treatment
Helicobacter pylori	Gastric	Disruption of the cellular mechanism via tyrosine phosphorylation of SHP-2 and kinases mediated by CagA secretion Induction of epithelial vacuolization, T-cell activation, and proliferation by VacA	Endoscopic surveillance Antibiotics (amoxicillin, clarithromycin, metronidazole, tetracycline, tinidazole)
Epstein-Barr Virus (EBV)	Gastric	Viral integration into the host genome mediated by B cell Cell proliferation and migration promotion by Viral EBER-1 and -2 transcript ROS accumulation and subsequent DNA modification via viral EBNA1 induction CpG island methylation, tumor suppressor genes, and tumor-associated antigens inactivation via viral LMP2A Cancer proliferation, apoptosis inhibition, and IFN signaling suppression via EBV miRNAs	Immunotherapy (checkpoint inhibitors) Antivirals (acyclovir, ganciclocvir, valgancyclovir, omaciclovir, valomaciclovir, maribavir, cidofovir, thymidine derivatives)
Hepatitis B Virus (HBV)	Liver	Chromosomal instability, mutagenesis, and cis-activation of tumor-associated genes due to viral-host genome integration miRNA expression alteration, histone methyltransferases activity, and cell expressions pattern dysregulation by HBx protein	Vaccination Antiviral therapy (lamivudine, adefovir, entecavir, telbivudine, tenofovir, emtricitabine, standard, and PEG-IFN)
Hepatitis C Virus (HCV)	Liver	Interference in metabolic reprogramming of hepatocytes Activation of PI3K/AKT pathway by NS5A phosphoprotein Blockage of tumor suppressor gene activity by HCV proteins Activation of ROS by NOX-1 and -4 Activation of inflammatory pathways and cytokines	Reducing the risk of exposure (single-use needles for intravenous drug injection, protection during sexual intercourse) Antiviral therapy (simeprevir, sofosbuvir, ledipasvir-sofosbuvir, ombitasvir-paritaprevir-ritonavir-dasabuvir, sofosbuvir-velpatasavir, sofosbuvir-velpatasvir-voxilaprevir, glecaprevir-pibrentasvir, ribavarin)
Aspergillus spp.	Liver	Formation of DNA adducts via activation of microsomal enzymes by aflatoxins Clonal expansion of hepatocytes	Food safety and storage management (high temperature, gamma rays) Detoxification agent (bacteria: Pleurotus eryngii; plant extract: Adhatoda vasica Nees) Chemical treatment (novasil clay mineral, chlorophyll)
Opisthorchis viverrini	Bile Duct	Mechanical and chronic injury of biliary epithelial cells due to parasite attachment Inflammation due to parasite product secretion Abnormal growth of biliary cells caused by Ov-GRN-1 protein Anti-apoptotic mechanism induction via thioredoxin and thioredoxin peroxidase production Incomplete wound healing due to DNA damage and chromosomal instability Mutagenesis in canonical carcinogenesis pathways	Proper food preparation (avoid consumption of raw fish) Antiparasitic (praziquantel, albendazole)
Clonorchis sinensis	Bile Duct	Host biliary cell metaplasia due to chronic mechanical irritation by parasite attachment Oxidative stress, host transcriptome, proteome, and miRNA expression changes due to ESPs Host DNA damage by genotoxins Cell apoptosis deactivation and abnormal cholangiocytes proliferation due to lipid peroxidation	Proper food preparation (avoid consumption of raw fish) Antiparasitic (praziquantel, albendazole)
Fusobacterium nucleatum	Colorectal	Cytokine production activation via FadA–E-cadherin adhesion Macrophage infiltration and CDKN2A methylation Cell proliferation activation via β-catenin and Wnt pathway upregulation Cancer cell invasion via MMP-1, -9, and -13 production Host immune system evasion via attachment of Fap2 to immune cells	Antibiotics (piperacillin, amoxicillin-clavulanate, clindamycin, imipenem, metronidazole) Chemotherapy (COX-2 inhibitor, specific EP2 antagonist) Immunotherapy (anti-Fap2 antibody, CTLA-4, PD-1, miR-21 blockade, adoptive cell transfer)
Schitosoma haematobium	Bladder	Granulomatous host Th2 immune response induction via chronic egg deposition Urothelial cell proliferation and bladder angiogenesis by H03-H-IPSE protein Mutation, DNA damage, and sister chromatid exchanges via parasite metabolites Excessive cell proliferation due to FGFGR3 overexpression	Snail control Water treatment (chlorine) Antiparasitic (praziquantel, albendazole)
Human Papillomavirus (HPV)	Cervical	Tumor suppressor genes interference by E6 and E7 Cell cycle check point control inhibition Anti-apoptosis induction, DNA repair mechanism disruption, abnormal proliferation, cell cycle dysregulation KIF23, ITGAV, CDKN2A, CENPE, BUB1B, MAD2L1, CHEK1, cyclin, and cell cycle proteins upregulation at a late stage	Vaccination Protection during sexual intercourse Regular screening (Pap smears) Surgical procedure (cryotherapy, electrocautery, surgical removal, laser surgery)
Kaposi’s Sarcoma Herpesvirus (KSHV)	Kaposi’s Sarcoma	Proliferation of cancer cells by vFLIP Apoptosis prevention, vascular proliferation, and inflammation via vFLIP, vIL-6, and/or viral miRNAs	Reducing the risk of exposure (avoid unprotected sexual intercourse) HAART treatment (for HIV patients) Antiviral therapy (valgancilovir, foscarnet, zidovudine) Radiotherapy Immunotherapy Chemotherapy (liposomal anthracyclines) Inhibitor agent (mTOR inhibitor, proteasome inhibitor, paclitaxel, MMP inhibitor, anti-angiogenic agents)
Epstein-Barr Virus (EBV)	Lymphoma	Burkitt’s Lymphoma Apoptosis inhibition via p53 mutations Genetic instability due to ROS and NOX2 production via EBNA1 Lymphocyte immortalization regulation via EBNA2 B to lymphoblastic cell line generation due to chronic infection	Avoid body fluid transfer from infected patients Small molecule inhibitor (EBNA1 inhibitor, HDAC inhibitors, butyrate and GCV, bortezomib, CDKs inhibitors, PI3K inhibitors, BCL-2 inhibitors, mTOR inhibitors, ixazomib) Immunotherapy (immune checkpoint inhibitors) Cell therapy (monoclonal antibodies, T-cell therapy)
		Hodgkin’s Lymphoma Formation of multinucleated HRS cells from B lymphocytes Cell signal disruptions due to defective HRS cells Increased HRS cell survival due to LMP-1 and -2 expression Lymph node structure disruption and cytokine activity increment due to CIITA mutagenesis