Infection with certain viruses is associated with different human cancers  Unsplash
Biotechnology

Viruses and Cancer

Several viruses increase your risk of cancer.

Swati Sharma

Human tumor viruses are a group of six viruses -Epstein-Barr virus, human papillomavirus, hepatitis B virus, human herpes virus-8, human T lymphotropic virus type, and hepatitis C virus that attribute to an estimated 15 percent of all cancers occurring in human beings globally. The members of this group though similar in their ability to cause human cancers are very different in the genetic material they have, and their life cycle stages and also belong to different virus families.

The Hepatitis B virus is a DNA virus from the family hepadnaviridae and the Hepatitis C virus is an enveloped RNA virus belonging to the flavivirus family. Both viruses can be transmitted via blood and can result in acute and chronic hepatitis, cirrhosis, and liver failure. Liver infections resulting from hepatitis B/C virus can lead to liver cancer. The diagnosis usually is made late and patient survival is usually between 6 to 20 months after diagnosis. Depending on the extent of damage caused by cancer, treatments include surgical removal of the tumor, transplantation, embolization, chemotherapy, and radiotherapy.

Vaccine against hepatitis B,introduced in the 1980s, provides prevention against infection, however, due to factors, like the requirement of multiple doses, non-responders to vaccines, mutations in viral genes, and incomplete coverage in developing countries due to lack of proper healthcare systems there are still many challenges to be faced. Further investigations are being made to develop an effective oral vaccine. Interferon therapy and antiviral drugs are given to infected patients to prevent the development of hepatitis and other complications leading to hepatocellular carcinoma. Unfortunately for hepatitis virus C, not much success has been achieved in vaccine development because of the high mutation rate of its genome. Similarly, treatment and transplantation in case of hepatitis C viral infection are not as successful as hepatitis B virus.

“During many viral infections, the genetic material of the virus is integrated into the genome of host cells, this can result in certain alterations in the genetic makeup of these cells, turning them cancerous…further specific viruses infect only certain cells thus resulting in specific types of cancers only.“
Dr. Anita Saini (Asst Professor Microbiology, Maharaja Agarsen University).

Epstein-Barr virus ( EBV) and human herpes virus 8 ( HHVV) are both herpes viruses that have double-stranded  DNA as genetic material. EBV infection primarily occurs through the oropharyngeal cavity. It can infect B lymphocytes and epithelial cells. On infection, it exists in a latent state in cells where it can activate into the lytic cycle. Although most EBV infections are subclinical, it is linked with cancers like B and T cell lymphoma, stomach cancer, and nasopharyngeal carcinomas. Burkitt’s lymphoma is the most common childhood malignancy in central Africa while nasopharyngeal carcinoma has a high incidence in southern China. Multi-agent chemotherapy, radiation therapy, and surgery are standard procedures followed in case of EBV-associated cancers. Additionally, immune therapy through EBV -specific cytotoxic T cells has also been found to be successful but with limitations. Efforts are being made to develop subunit vaccines and recombinant vaccines that can boost the immune response against primary EBV infection as well as tumors associated with it.

Human Herpes Virus-8 ( also called Kaposi sarcoma-associated Herpes virus) predominantly infects B lymphocytes and can be transferred through saliva, blood transfusion,  sexual contact, and organ transplantation. It can result in Kaposi sarcoma (a vascular malignancy) and B-cell lymphoproliferative diseases. Antiviral agents like ganciclovir are used to prevent the proliferation of this virus.

Factors like requirement of multiple doses, individuals that do not respond to vaccine and mutating viral genomes hinder vaccine development against viral infections that are associated with malignancies

Human Papillomavirus (HPV) is a small non-enveloped DNA virus that infects epithelial cells. Its infection in humans commonly causes benign papilloma or warts, however, persistent infection can result in cervical cancer and head and neck tumors, and skin cancers in immunosuppressed patients. Cervical cancer accounts for the second highest cancer mortality in women, the majority of which occur in developing countries. The therapies include chemotherapy and radiotherapy which provide only temporary cures and are associated with many toxicities. Immune response against HPV infection plays an important role in preventing the formation of cancer, however poor immune responses may lead to increased rates of infection resulting in cervical cancer. Pap tests can be used to screen pre-cancerous virus-infected cells which can be destroyed or removed to prevent cancer from developing. The HPV vaccine is recommended for children ages 9 to 12 to protect against HPV infection.

Human T lymphotropic virus type -I ( HTLV-I) is a retrovirus with a single-stranded RNA genome. It can be transmitted by blood transfusion, sexual contact, and during parturition. HTLV -1 infection results in adult T- cell leukemia in 5% of infected individuals.

It may remain latent for a long duration of 20-30 years before the onset of cancer, after which it progresses rapidly. Although chemotherapy is successful in the initial stages, there are chances of relapse. Host-specific factors ( CD8 T cytotoxic cells) play an important role in transforming HTLV -I infected cells. Studies are being done to develop targeted therapies that can result in the generation of neutralizing antibodies or better cytotoxic T-cell response against HTLV-I infection.

Vaccines to prevent preceding infections and targeted therapies against viral proteins or immune response against virus infected cells are strategies that can help in preventing viral infection related cancers

Apart from this list, Human Immunodeficiency Virus ( HIV), and Merkel cell polyomavirus (MCV) are also associated with certain human cancers. Viral infection alone does not lead to cancer. It is the presence of various environmental and host factors such as the presence of carcinogens, genetic predisposition, mutations, and poor or suppressed immunity that can gradually lead from viral infection to tumorigenesis.  Not all individuals infected by these viruses progress to a cancerous state, it is only in a minority of cases that these infections complemented by promoting factors result in cancer development.

Studies focused on understanding these viruses, their life cycle stages, evolution, and infection of host cells, have resulted in interventions to prevent precancerous infections that may cause carcinogenesis

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