J Natl Cancer Inst. Presence and activity of HPV in primary lung cancer. J Cancer Res Clin Oncol. Viral Hepatitis. Updated September 10, Wong Ch, Goh K.
Chronic hepatitis B infection and liver cancer. Biomed Imaging Interv J. Viral hepatitis, Hepatitis C questions and answers for health professionals.
Updated July 2, Viral Hepatitis: Testing recommendations for hepatitis C virus infection. Updated October 15, Epstein-Barr virus-associated lymphomas. Posttransplant Epstein-Barr virus related lymphoproliferative disorder with a primary cutaneous presentation. Dermatol Online J. American Cancer Society. Updated July 25, Saha A, Robertson ES.
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National Cancer Institute. Infectious Agents. Updated March 4, Early-life exposures to infectious agents and later cancer development. Cancer Med. Your Privacy Rights. To change or withdraw your consent choices for VerywellHealth. At any time, you can update your settings through the "EU Privacy" link at the bottom of any page.
These choices will be signaled globally to our partners and will not affect browsing data. We and our partners process data to: Actively scan device characteristics for identification. I Accept Show Purposes. Table of Contents View All. Boys and girls age should get the HPV vaccine. It is spread through infected semen, vaginal fluids, blood and breast milk. The infection is rarely found in the United States.
The effects of these viruses on cancer development is highly complicated. This can cause the host cells to become cancerous. If you think you may have or be at risk for an oncovirus, talk to your doctor about reducing your cancer risk. My Chart. Donate Today. For Physicians. Cancer Moonshots. August 7 viruses that cause cancer. Previous Article. Next Article.
August : 7 viruses that cause cancer. How do viruses cause cancer? What can people do to avoid getting these cancer-causing viruses? You can take steps to reduce your risk of getting oncoviruses. Get vaccinated. The hepatitis B vaccine can help reduce your liver cancer risk. Get screened. In addition, follow our cancer screening guidelines.
The viral genome is expressed in these tumors and encodes transforming proteins and anti-apoptotic factors. The virus is also able to enhance the proliferation of microvascular endothelial cells [ 34 ]. As with EBV, the predominant infected cell is the B lymphocyte, although here the lytic cycle is embraced rather than repressed. This may play a crucial role in the pathogenesis of Kaposis sarcoma by elaboration of viral and host cytokines promoting cell proliferation, angiogenesis, and enhancement of viral spread.
Targeted antiviral agents such as ganciclovir directed against viral DNA replication have had a dramatic affect on decreasing the incidence of Kaposi sarcoma in AIDS patients through both therapy and prophylaxis [ 35 ].
Furthermore, a G protein coupled receptor vGPCR has been identified as a viral oncogene in HHV-8 infected cells that can exploit cell signaling pathways to induce transformation and angiogenesis [ 36 ].
But the therapy regimen most responsible for the decreasing incidence of Kaposi sarcoma may well be the success of highly active antiretroviral therapy HAART regimens targeting HIV [ 38 ], since it was the emergence of HIV that led to the increasing incidence of Kaposi sarcoma. HPV are small non-enveloped DNA tumor viruses that commonly cause benign papillomas or warts in humans.
Persistent infection with high-risk subtypes of human papillomavirus HPV is associated with the development of cervical cancer [ 39 ]. HPV infects epithelial cells, and, after integration in host DNA, the production of oncoproteins, mainly E6 and E7, disrupts natural tumor suppressor pathways and is required for proliferation of cervical carcinoma cells [ 40 ].
HPV also is believed to play a role in other human cancers, such as head and neck tumors, skin cancers in immunosuppressed patients, and other anogenital cancers. Cervical cancer is the second leading cause of cancer mortality in women worldwide, causing , deaths annually [ 41 ]. Of approximately , cases reported each year, more than 80 percent occur in the developing world, where effective but costly Pap smear screening programs are not in place [ 41 ].
Early precancerous changes and early cancers detected by Pap smears are effectively treated and cured with surgical therapy or ablation. In the absence of effective screening, the disease is detected late. Traditional therapeutic options for cervical cancer that have advanced beyond definitive surgical treatment are chemotherapy and radiation therapy, which are associated with many toxicities and do not offer a lasting cure.
The immune system plays an important role in the prevention of persistent HPV infection and progression of precancerous lesions. Human papillomavirus is a poor natural immunogen; as a double stranded DNA virus, there is no RNA intermediate, nor does infection cause cytolysis, allowing initiation of innate immune responses [ 42 ].
HPV mainly encodes non-secreted nucleoproteins, which are poorly cross-presented and compared to other viruses its non-structural proteins are expressed at low levels. However, genital infection with HPV is usually transient.
Additionally, inadequate T cell responses may lead to failure to clear HPV-infected cells. AIDS patients, renal transplant patients receiving immunosuppressive therapy, and individuals with T cell deficiencies have increased rates of HPV persistence, anogenital lesions, and cervical cancer [ 43 - 46 ]. In , an effective prophylactic vaccine against HPV 16 and 18 based on virus-like particles VLP of recombinant L1, the major capsid protein [ 47 , 48 ], was approved for use by the FDA based on clinical trials that demonstrated nearly percent protection from persistent infection through the generation of high levels of neutralizing antibodies.
Since these types are the causative agent of approximately 70 percent of cervical cancers, development of such an effective vaccine holds much promise for the prevention of cervical cancer [ 47 ]. Because of these limitations, therapeutic vaccination is being explored to treat women already infected and accelerate the impact of prophylactic vaccination in decreasing cervical cancer incidence. Traditional therapy for early cervical cancer and precancerous lesions involves surgical excision or ablation.
Therapeutic vaccination seeks to generate a population of cytoxic T cells that will recognize and kill tumor cells. Since patients with T cell deficiencies are known to be more susceptible to HPV infection and disease progression, boosting T cell responses to HPV may be crucial to a therapeutic immune strategy.
In the case of cervical cancer, E6 and E7 oncoproteins are expressed in all malignancies and are not found in uninfected normal cells. Therefore, they represent ideal targets for a therapeutic immune response. A number of strategies to generate immune responses against these antigens are under investigation.
Viral and bacterial vectors have been used in mouse models to generate immune responses. Vaccinia virus delivery of HPV 16 and 18 modified E6 and E7 proteins has demonstrated safety and specific immune responses in early clinical trials [ 49 ].
DNA vaccination strategies also are under active investigation, and several are in various stages of clinical trials. Vaccination with plasmid DNA encapsulated in biodegradable micorparticles has shown histological and immunological responses when used to treat patients with high grade cervical dysplasia [ 50 - 52 ].
It possesses a diploid genome similar to other retroviruses: two long terminal repeats flanking gag, pol, and env genes as well as a number of accessory genes. HTLV-1 has a worldwide distribution, with an estimated 12 to 25 million people infected.
However, disease is only observed in less than 5 percent of infected individuals. It is transmitted through blood transfusions, sexual contact, and during parturition. HTLV-1 displays a special tropism for CD4 cells, which clonally proliferate in adult T cell leukemia, though how this is effected is not known. HTLV-1 infection has a very long latency period of 20 to 30 years, but once tumor formation begins, progression is rapid.
Standard chemotherapy often can bring about an initial response with a partial or complete remission; however, relapse is common, and median survival is eight months.
The HTLV-1 Tax gene has been postulated to play an important role in tumorgenesis [ 54 ] through the activation of viral transcription and the hijacking of cellular growth and cell division machinery, but the mechanisms leading to adult T cell leukemia are not well understood. It has been suspected that HTLV-1 infection may not be sufficient to transform, and recent evidence suggests that the decreased diversity, frequency, and function of HTLV-1 specific CD8 T cells in the host may play an important part in the development of adult T-cell leukemia [ 55 ].
Therefore, targeted therapies using peptide, recombinant protein, DNA, and viral vectors with the goal of generating neutralizing antibody against HTLV-1 and multivalent cytotoxic T cell response against Tax are under investigation [ 56 ].
The viruses reviewed here illustrate the diverse biological pathways to malignancy and the challenges of treating the resulting diseases. Yet the presence of the viral gene products in cancer and precancerous cells present attractive targets that may be exploited in novel therapies that distinguish these cells from normal cells. Antivirals such as lamuvidine used in heptatitis B and ganciclovir for Kaposi sarcoma specifically target the viral replication machinery.
Targeting cancer cells specifically would have advantages over traditional modalities such as chemotherapy and radiation, which can include significant toxicities. Cervical cancer, because it retains HPV viral oncoproteins E6 and E7 and requires their continued expression for proliferation, provides an ideal model for cytotoxic immune therapies against these known antigens.
Given the prevalence of these cancers in the developing world and the limitations of health care infrastructure, strategies for vaccine design to prevent primary infection and targeted therapies for the treatment of disease must be carefully considered in this context. Use of needles, refrigeration, multiple doses, and cost are all significant barriers to the delivery of an effective vaccine [ 41 ].
Cost, need for trained personnel and sophisticated equipment and facilities may impede global use of the most advanced targeted therapies. These challenges suggest that exploration of prophylactic strategies and development of specific, targeted therapies are both necessary to decrease this portion of the global cancer burden.
National Center for Biotechnology Information , U. Yale J Biol Med. John B Liao. Author information Copyright and License information Disclaimer. To whom all correspondence should be addressed: John B. Box , New Haven, CT Tel: ; Fax: ; E-mail: ude.
John B. This is an open access article distributed under the terms of the Creative Commons CC BY-NC license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited. You may not use the material for commercial purposes. This article has been cited by other articles in PMC. Human tumor viruses Although it is convenient to consider human tumor viruses as a discrete group of viruses, these six viruses, in fact, have very different genomes, life cycles, and represent a number of virus families.
Summary The viruses reviewed here illustrate the diverse biological pathways to malignancy and the challenges of treating the resulting diseases. Acknowledgments I would like to thank Daniel DiMaio for his critical reading of this manuscript.
References zur Hausen H. Viruses in human cancers. Hepatitis C: global prevalence. Wkly Epidemiol Rec.
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