VIRUS INDUCED CANCER

Guided by,
Anjali D Ganjiwale
Asst. professor
Dept of Life science
Bangalore university
Presented by,
Chaitra M K
Dept of Life science
Bangalore university
AGENDA
Introduction
History
Types
Controlling measures
Review of literature
 Introduction
 Viruses generally have specific host cells which they infect. Some virus types are associated with specific
cancers and can convert normal cells into cancer cells. Examples of viruses associated with cancer are:
papillomavirus-cervical cancer, hepatitis virus-liver cancer, Epstein-Barr virus-Burkitt's lymphoma.
 Viruses are very small 'organisms' that can infect the cells of other animals or plants. Humans are
susceptible to a large number of different viruses. Viruses are not the same as bacteria although both can
cause human disease. Some examples of viruses include the agent that causes the flu (influenza virus)
and the causative agent of AIDS, the human immunodeficiency virus (HIV). The viruses may contain
their own genes that disrupt the regulation of the cell. This process may be beneficial to the virus if it
allows for rapid production of progeny but can be seriously detrimental to the host.
 Some viruses actually carry altered versions of genes that they have picked up from previous host cells.
These altered genes no longer function properly, and when they are inserted into a new host cell, they
cause disregulation and can lead to cancerous growth.
 Through their mutagenic activity or their effects on cell behavior, viruses play a significant role in the
development of particular cancers in many different animals, including humans.
 Viruses have also been a major target of scientific investigation with respect to cancer. Some of the
earliest work on the identification of oncogenes and tumor suppressors utilized viruses.
 Viruses can be divided into two rough categories, those that have DNA as their genetic material and those
that have RNA as their genetic material. Both kinds of virus have been found to be associated with
cancers of different types.
History
The concept of cancer was first described around 3000BC, But the role infectious disease
plays in different cancers has been appreciated for only a century. Scientists now
recognize that are both environmental and biological factors that development of
cancer.
 Environmental factors: Exposure to DNA- damaging chemicals such as cigarette smoke,
formaldehyde and asbestos play roles in cancer development
 Genetic factors: risk for inherited diseases, such as breast colon endometrial and
ovarian cancers can be passed down in families
 Infectious disease :microbial infections can lead to cancer such as lymphoma,
carcinoma and leukemia tumor virology has also helped us develop prophylactic
vaccine (such as those for hepatitis B virus and human papilloma virus).
 The first infectious source of cancer was discovered in 1911, when a virus was first
associated with cancer in chickens. Frances peyton Rous, a virologist at Rockefeller
institute for Medical Research, transferred bacteria-free and cell- free extracts from a
chicken with a lump in the breast to a healthy chicken.
 In 1935 Richard schope reported a papilloma virus that cause tumors in rabbits.
How does a normal cell become cancerous
 The growth and division of normal cell is regulated by at least two types of genes,
namely, proto oncogenes and tumor suppressor genes. The former promote growth
but they function under the control of the latter which are growth-restrainting.
Changes in either or both types of these genes results in an uncontrolled growth
and, therefore ,to cancer.
 Scientist believe that there are many cause of cancer. Possibly as many as 30-60% of
cancer may be related of diet. Many chemicals are carcinogenic and may cause
cancer by inducing gene mutations or interfering with normal cell differentiation.
 Gene mutation may also results in by physical stimuli such as ultraviolet radiation
or x-ray. However, some viruses are thought to be directly related to cancer as they
bring about the genetic change that results in initiation of tumor formation.
 The human T-cell lymphotropic viruses appear to transform cell into tumor cell by
producing a regulatory protein that sometimes activates gene related to cell division
as well as virus posses one or more very effective promoters or enhancers.
 Types
Hepatitis B Virus (HBV) - Liver Cancer
Prevalence: HBV is prevalent on every continent, but is especially high in sub-Saharan
Africa and Southeast Asia. It is estimated that over 400 million people worldwide are
infected.
Transmission: HBV is transmitted via contact with contaminated blood, sweat, or
tears. It can also be spread through sexual contact and from mother to child.
Infection: HBV Infection occurs mainly in the liver, but viral antigens can be detected
in the blood throughout the body. Chronic Infection is indicated by the presence of
viral antigens in the blood for longer than 6 months. Chronic Infection can lead to
cirrhosis of the liver and development of HCC.
Carcinogenic Potential: Hepatitis viruses (B and C) are responsible for 70-85% of
primary liver cancers. Viral integration into the host genome is regularly found in
chronic liver infection and cancer. This suggests it plays an important role in
carcinogenesis. HBV encodes a protein (HBX) that may promote cell proliferation and
interfere with DNA repair. HBV mediated carcinogenesis is likely due to a number of
factors; the oncogenic properties of HBX, chronic liver damage, chronic inflammation,
and the continuous tissue regeneration needed to maintain the liver during an
infection.
Human T-cell Lymphotropic Virus 1 (HTLV) -
Adult T-cell Leukemia
Prevalence: Approximately 10 to 20 million people are infected worldwide.
HTLV-1 is endemic in southwest Japan, in and around the Caribbean islands,
in parts of Central Africa and South America.
Transmission: HTLV1 can be transmitted via sexual or blood-blood contact.
It can also be passed through breast milk and from mother to fetus.
Infection:
Carcinogenic Potential: About 3-5% of people with HTLV1 will develop adult
T-cell leukemia, with most cases occurring in middle aged people. At least
one of HTLV1's regulatory proteins, (Tax), is thought to be involved with
ATLL development. Tax may contribute to carcinogenesis by inducing
cellular proliferation, activating cell survival proteins, and also may
contribute to chromosomal instability.
Several other retroviruses are also associated with cancer and the use of
retroviral vectors in cancer treatment has to take into consideration the
possibility that the treatments could cause major problems.
Human Papillomavirus (HPV)
 The human papillomavirus is transmitted via skin-skin contact. Sexual intercourse is not
necessary for transmission, but is the most common route. The virus can infect the
genital, anal, and oral regions of the body. Infection occurs when viruses enter into small
breaks in the skin or mucous membranes. The probability of acquiring HPV from a single
sexual encounter is not known, but is probably high.
 The human papillomavirus is the primary risk factor for cervical cancer. It is responsible
for at least 90% of cases. High risk HPV type 16 is the most common high-risk type and is
found in over 50% of cervical cancers. The second most common high-risk type is 18 and
it is responsible for 10-12% of cervical cancers. Although HPV responsible for virtually all
cases of cervical cancer, 80% of women clear an infection within 1-2 years.
 HPV invades the skin or mucosa by entering tiny breaks in the surface (even those not
visible to the naked eye). Once inside, HPV infects host epithelial cells, tricking them
into producing new viruses. In the process of normal cell replacement, the infected cells
are shed, releasing viral particles. High risk strains of HPV can integrate viral DNA into
the host genome, although this is not a normal part of the HPV life cycle. Viral
integration may give infected host cells a selective advantage, leading to a longer infection
time. The longer the infection lasts, the more time there is for cancer to develop.
 Human Herpesvirus 8 (HHV8)
 Associated Cancer: HHV8 primarily causes Kaposi's Sarcoma (KS), a
type of cancer that affects the skin and soft organs. HHV8 is also
associated with several blood disorders.
Prevalence: HHV8 is uncommon in most of the world, only 1-5% of
people in North America and Northern Europe are infected.
Mediterranean populations have a higher infection rate (5-20%) and
Sub-Saharan Africa has the highest rate (>60%). In the U.S., gay men
also have a higher infection rate (~40%).
Transmission: HHV8 is most commonly spread through sexual
contact and via saliva. Transmission also may occur via organ
transplantation or blood transfusion.
Infection: HHV8 infects B cells, epithelial cells, endothelial cells and
possibly monocytes. HHV8 infection is high in populations with
high incidence of KS and low in populations with low incidence of
KS.
Carcinogenic Potential: HHV8 DNA is found in all cases of KS, but
infection is not enough to cause cancer. The exact method by which
HH8V induces cancer is still under investigation. KS probably starts
as an inflammatory process to which circulating cells (including
HHV8 infected cells) are recruited, leading to further inflammation,
tissue damage, and viral infection. HHV8 then establishes a
persistent infection which may send signals
promoting angiogenesis and inflammation. This cycle may
ultimately lead to tumor development. Untreated AIDS confers a
20,000 fold higher risk of developing KS, but other than
immunosuppression the role of AIDS is generally unknown.
Skin Cancer (Merkel Cell Carcinoma)
 Merkel cells are located in the outer layer of
skin (epidermis) and their exact function is
not known. They appear to have sensory roles
(i.e. detecting textures) and may have other
functions.
 Merkel cell polyomavirus (MCV or MCPyV)
has been linked to a form of skin cancer that
affects Merkel cells - Merkel cell carcinoma.
Whether the virus causes the cancer is not
entirely clear. Researchers are also looking to
see if MCV is associated with other types of
skin cancer (squamous cell carcinoma - SCC
and basal cell carcinoma - BCC).
 The images below, in clockwise order - a
Merkel cell tumor, Merkel cell cancer as
viewed under a microscope, virus-like
particles from MCV, .
 Controlling measures
 1. Don't use tobacco
 Using any type of tobacco puts you on a collision course with cancer. Smoking has been linked to
various types of cancer — including cancer of the lung, mouth, throat, larynx, pancreas, bladder,
cervix and kidney. Chewing tobacco has been linked to cancer of the oral cavity and pancreas. Even if
you don't use tobacco, exposure to secondhand smoke might increase your risk of lung cancer.
 2. Eat a healthy diet
 Although making healthy selections at the grocery store and at mealtime can't guarantee cancer
prevention, it might reduce your risk. Consider these guidelines:
 Eat plenty of fruits and vegetables. Base your diet on fruits, vegetables and other foods from plant
sources — such as whole grains and beans.
 Maintain a healthy weight. Eat lighter and leaner by choosing fewer high-calorie foods, including
refined sugars and fat from animal sources.
 If you choose to drink alcohol, do so only in moderation The risk of various types of cancer —
including cancer of the breast, colon, lung, kidney and liver — increases with the amount of alcohol
you drink and the length of time you've been drinking regularly.
 Limit processed meats. A report from the International Agency for Research on Cancer, the cancer
agency of the World Health Organization, concluded that eating large amounts of processed meat
can slightly increase the risk of certain types of cancer.
 In addition, women who eat a Mediterranean diet supplemented with extra-virgin olive oil and mixed
nuts might have a reduced risk of breast cancer. The Mediterranean diet focuses mostly on plant-
based foods, such as fruits and vegetables, whole grains, legumes, and nuts. People who follow the
Mediterranean diet choose healthy fats, such as olive oil, over butter and fish instead of red meat.
 3. Maintain a healthy weight and be physically active
 Maintaining a healthy weight might lower the risk of various types of cancer, including cancer of the
breast, prostate, lung, colon and kidney.
 Physical activity counts, too. In addition to helping you control your weight, physical activity on its
own might lower the risk of breast cancer and colon cancer.
 Adults who participate in any amount of physical activity gain some health benefits. But for
substantial health benefits, strive to get at least 150 minutes a week of moderate aerobic activity or 75
minutes a week of vigorous aerobic activity. You can also do a combination of moderate and vigorous
activity. As a general goal, include at least 30 minutes of physical activity in your daily routine — and
if you can do more, even better.
 4. Protect yourself from the sun
 Skin cancer is one of the most common kinds of cancer — and one of the most preventable. Try these
tips:
 Avoid midday sun. Stay out of the sun between 10 a.m. and 4 p.m., when the sun's rays are strongest.
 Stay in the shade. When you're outdoors, stay in the shade as much as possible. Sunglasses and a
broad-brimmed hat help, too.
 Cover exposed areas. Wear tightly woven, loose fitting clothing that covers as much of your skin as
possible. Opt for bright or dark colors, which reflect more ultraviolet radiation than do pastels or
bleached cotton.
 Don't skimp on sunscreen. Use a broad-spectrum sunscreen with an SPF of at least 30, even on
cloudy days. Apply sunscreen generously, and reapply every two hours — or more often if you're
swimming or perspiring.
 Avoid tanning beds and sunlamps. These are just as damaging as natural sunlight.
 5. Get vaccinated
 Cancer prevention includes protection from certain viral infections. Talk to your doctor about
vaccination against:
 Hepatitis B. Hepatitis B can increase the risk of developing liver cancer. The hepatitis B vaccine is
recommended for certain adults at high risk — such as adults who are sexually active but not in a
mutually monogamous relationship, people with sexually transmitted infections, people who use
intravenous drugs, men who have sex with men, and health care or public safety workers who might
be exposed to infected blood or body fluids.
 Human papillomavirus (HPV). HPV is a sexually transmitted virus that can lead to cervical and
other genital cancers as well as squamous cell cancers of the head and neck. The HPV vaccine is
recommended for girls and boys ages 11 and 12. The U.S. Food and Drug Administration recently
approved the use of vaccine Gardasil 9 for males and females ages 9 to 45.
 6. Avoid risky behaviors
 Another effective cancer prevention tactic is to avoid risky behaviors that can lead to infections that,
in turn, might increase the risk of cancer. For example:
 Practice safe sex. Limit your number of sexual partners and use a condom when you have sex. The
more sexual partners you have in your lifetime, the more likely you are to contract a sexually
transmitted infection — such as HIV or HPV. People who have HIV or AIDS have a higher risk of
cancer of the anus, liver and lung. HPV is most often associated with cervical cancer, but it might also
increase the risk of cancer of the anus, penis, throat, vulva and vagina.
 Don't share needles. Sharing needles with people who use intravenous drugs can lead to HIV, as
well as hepatitis B and hepatitis C — which can increase the risk of liver cancer. If you're concerned
about drug misuse or addiction, seek professional help.
7. Get regular medical care
Regular self-exams and screenings for various types of
cancers — such as cancer of the skin, colon, cervix and
breast — can increase your chances of discovering
cancer early, when treatment is most likely to be
successful.
 Review of literature
 HCV Infection occurs mainly in the liver and produces a more severe inflammation than HBV.
Over 80% of those infected with HCV will develop cirrhosis of the liver or HCC. occardo and LL
Villa. Viral Origins of Human Cancer. Current Medicinal Chemistry. 2007; 24: 2526-39.
 HTLV-1 is an RNA virus (a retrovirus) that can infect T-cells, B-lymphocytes, monocytes, and
fibroblasts . Masao Matsuoka and Kuan-Teh Jeang. Human T-Cell Leukemia Virus Type I at Age
25: A Progress Report. Cancer Research. 2005; 65(11):4467-70.
 HBV Infection occurs mainly in the liver, but viral antigens can be detected in the blood
throughout the body. Chronic Infection is indicated by the presence of viral antigens in the
blood for longer than 6 months. Chronic Infection can lead to cirrhosis of the liver and
development of HCC . Lupberger J, Hildt E. Hepatitis B virus-induced oncogenesis. World J
Gastroenterol. 2007 Jan 7;13(1):74-81.
 Merkel cell polyomavirus (MCV or MCPyV) has been linked to a form of skin cancer that affects
Merkel cells. Ganzenmueller T, Yakushko Y, Kluba J, Henke-Gendo C, Gutzmer R, Schulz TF. Next-
generation sequencing fails to identify human virus sequences in cutaneous squamous cell carcinoma Int J
Cancer. 2012 Apr 5. doi: 10.1002/ijc.27581.
 Infection with the human papillomavirus is asymptomatic (doesn't have symptoms). In most cases HPV
doesn't cause any problems and is cleared by the immune system. zur Hausen H. Papillomaviruses and
cancer: from basic studies to clinical application. Nature Reviews. Cancer. 2002; 2(5):342-50
 Viruses have also been a major target of scientific investigation with respect to cancer. Some of the earliest work on the
identification of oncogenes and tumor suppressors utilized viruses.1Cooper G. Oncogenes. Jones and Bartlett
Publishers, 1995. 151-152, 175-176