Viruses and cancer

Cancer and Viruses
ASPEC /May 3 2021 / Robert
Miller MD

CANCER AND
VIRUSES
- How many cancers are due to virus
infections?
- Which viruses and cancers are
linked?
- Does this mean it’s contagious?
- Can you use vaccines to prevent
these cancers?

Between 30-50% of all cancer cases are preventable. Prevention offers the most
cost-effective long-term strategy for the control of cancer.
Cancer causing infections, such as hepatitis and human papilloma virus (HPV), are
responsible for up to 25% of cancer cases in low- and middle-income countries
Vaccines are available for hepatitis B virus and some types of HPV, and can reduce
the risk of liver and cervical cancers, respectively.

Certain infectious agents, including viruses, bacteria, and parasites, can cause
cancer or increase the risk that cancer will form.
Some viruses can disrupt signaling that normally keeps cell growth and proliferation in
check
Some infections weaken the immune system, making the body less able to fight off
other cancer-causing infections.
Some viruses, bacteria, and parasites also cause chronic inflammation which may
lead to cancer

Most of the viruses that are linked to an increased risk of cancer can be
passed from one person to another through blood and/or other body
fluids.
You can lower your risk of infection by getting vaccinated, not having
unprotected sex, and not sharing needles.

•Epstein-Barr Virus (EBV)
•Hepatitis B Virus and Hepatitis C Virus (HBV and HCV)
•Human Immunodeficiency Virus (HIV)
•Human Papillomaviruses (HPVs)
•Human T-Cell Leukemia/Lymphoma Virus Type 1 (HTLV-1)
•Kaposi Sarcoma-Associated Herpesvirus (KSHV)
•Merkel Cell Polyomavirus (MCPyV)
•Helicobacter pylori (H. pylori)
•Opisthorchis viverrini
•Schistosoma hematobium

Cancer Viruses: Classes
There are two classes of cancer viruses: DNA and RNA viruses.
DNA Viruses
The Epstein-Barr virus has been linked to Burkitt's lymphoma.
The hepatitis B virus has been linked to liver cancer in people with chronic
infections.
Human papilloma viruses have been linked to cervical cancer.
Human herpes virus-8 has been linked to the development of Kaposi sarcoma.
Merkel cell polyomavirus (MCPyV) is a nonenveloped, double-stranded DNA virus
RNA Viruses
Human T lymphotrophic virus type 1 (HTLV-I), a retrovirus, has been linked to T-
cell leukemia.
The hepatitis C virus has been linked to liver cancer in people with chronic

Epstein-Barr Virus (EBV)
EBV, a type of herpes virus, causes mononucleosis as well as certain types
of lymphoma (Africa)and cancers of the nose and throat (nasopharynx in Asians).
EBV is most commonly transmitted by contact with saliva (kissing) also can be
spread by sexual contact, blood transfusions, and organ transplantation. EBV
infection is lifelong. More than 90% of people worldwide will be infected with EBV
during their lifetime, and most do not develop any symptoms.
There is no vaccine to prevent EBV infection and no specific treatment for EBV
infection.

Burkitt Lymphoma from EBV
Virus
Burkitt lymphoma (BL), which is characteristically
localized in the jaw, is the most common childhood
malignancy in equatorial Africa. More than 95
percent of African children are infected with EBV
by age three, whereas, in affluent countries,
primary infection is often delayed until adolescence
Malaria and EBV infection are considered
cofactors in the genesis of Burkitt lymphoma.

Virus % of Cancer Cancer Types
Hepatitis (HBV and
HCV)
4.9% Hepatocellular
Human T-lymphotropic
(HTLV)
.03% Adult T cell leukemia
Human Papillomavirus
(HPV)
5.2% Cervix, Anus, Vulva,
Vagina, Oropharynx
Kaposi sarcoma
associated herpesvirus
(HHV-8)
0.9% Kaposi sarcoma, multicentic
Castleman, primary effusion
lymphoma
Merkel cell
polyomavirus
NA Merkel cell
Epstein-Barr (EBV) NA Burkitt, nasopharynx
Human Cancer Viruses

Chronic infections with HBV or HCV can cause liver cancer. Both viruses can be
transmitted via blood (for example, by sharing needles or through blood
transfusions) and from mother to baby at birth. In addition, HBV can be transmitted
via sexual contact.
Since the 1980s, infants in the United States and most other countries have been
routinely vaccinated against HBV infection. Experts recommend that adults who
have not been vaccinated against HBV and are at increased risk of HBV infection
get vaccinated
(CDC) also recommends that everyone in the United States born from 1945 through
1965, and other populations at increased risk for HCV infection, be tested for HCV.
Although there is not currently a vaccine against HCV, new therapies can cure
Hepatitis B Virus and Hepatitis C
Virus (HBV and HCV)

Long term liver inflammation leads to liver
cancer
There are vaccines to prevent
hepatitis A and hepatitis B;
however, no vaccine is available
for hepatitis C.
Hep A is not linked to cancer.

Human Immunodeficiency Virus
(HIV)
HIV is the virus that causes acquired immunodeficiency syndrome (AIDS). HIV does
not cause cancer itself, but infection with HIV weakens the immune system and
makes the body less able to fight off other infections that cause cancer.
People infected with HIV have increased risks of a number of cancers,
especially Kaposi sarcoma, lymphomas (including both non-Hodgkin lymphoma and
Hodgkin disease), and cancers of the cervix, anus, lung, liver, and throat.

Other infections that cause cancer
Human T-Cell Leukemia/Lymphoma Virus Type 1 (HTLV-1)
HTLV-1 can cause an aggressive type of non-Hodgkin lymphoma called adult T-cell leukemia/lymphoma (ATLL).
Kaposi Sarcoma-Associated Herpesvirus (KSHV)
Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8), can cause Kaposi
sarcoma.
Merkel Cell Polyomavirus (MCPyV)
MCPyV can cause Merkel cell carcinoma, a rare type of skin cancer.
Helicobacter pylori (H. pylori)
H. pylori is a type of bacterium that can cause noncardia gastric cancer (a type of stomach cancer) and a type of
lymphoma in the stomach lining, gastric MALT lymphoma. It can also cause stomach ulcers.
Opisthorchis viverrini
This parasitic flatworm (fluke), which is found in Southeast Asia, can cause cholangiocarcinoma (cancer of the bile
ducts in the liver).
Schistosoma hematobium
This parasitic flatworm (fluke), which lives in certain types of freshwater snails found in Africa and the Middle East,

KS LESIONS IN AIDS
Tom Hanks in the movie Philadelphia

KAPOSI SARCOMA
Kaposi sarcoma (KS) is a vascular tumor that is etiologically associated with
human herpesvirus 8 (HHV-8), which is also known as the KS-associated
herpesvirus (KSHV). Although KS has been reported among all risk groups
for HIV infection, it is most common in homosexual or bisexual men. AIDS-
related KS is much less common in heterosexual injection drug users,
transfusion recipients, women or children, and hemophiliacs
In patients with AIDS-related KS, the CD4 count appears to be the most
important factor associated with the development of KS.

Rare infections that cause cancer
Human T-Cell Leukemia/Lymphoma Virus Type 1 (HTLV-1)
HTLV-1 can cause an aggressive type of non-Hodgkin lymphoma called adult T-cell leukemia/lymphoma (ATLL).
Kaposi Sarcoma-Associated Herpesvirus (KSHV)
Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8), can cause Kaposi
sarcoma.
Merkel Cell Polyomavirus (MCPyV)
MCPyV can cause Merkel cell carcinoma, a rare type of skin cancer.
Helicobacter pylori (H. pylori)
H. pylori is a type of bacterium that can cause noncardia gastric cancer (a type of stomach cancer) and a type of
lymphoma in the stomach lining, gastric MALT lymphoma. It can also cause stomach ulcers.
Opisthorchis viverrini
This parasitic flatworm (fluke), which is found in Southeast Asia, can cause cholangiocarcinoma (cancer of the bile
ducts in the liver).
Schistosoma hematobium
This parasitic flatworm (fluke), which lives in certain types of freshwater snails found in Africa and the Middle East,

FRIEDRICH SIGMUND MERKEL
(5 APRIL 1845 – 28 MAY 1919)
German anatomist and
pathologist of the late
19th century.
associated with the sense of light touch
discrimination of shapes and textures. they contain
dense core granules, and thus may also have
a neuroendocrine function.
Merkel Cell

MERKEL CELL
Merkel cell carcinoma (MCC) of the skin is a rare, aggressive cutaneous
malignancy that predominantly affects elderly Caucasians and has a
propensity for local recurrence and regional lymph node metastases.
Merkel cell polyomavirus is a non-enveloped, double-stranded DNA virus that
may be causally linked to the development of MCC.

Has increased 540% in the last
18 years

• Rare, aggressive tumor (but incidence is dramatically increasing) 26-
36% have lymph node spread and 6-16% present with metastases
• 5 Year survival is 41 to 77%
• More common in older white men, with high sun exposure and in
immunosuppressed and are frequently misdiagnosed
• MCC incidence increases exponentially with advancing age, from 0.1 to
1 to 9.8 (per 100,000 person-years) among age groups 40 to 44, 60 to
64, and >85 years
• The Merkel Cell Polyomavirus (MCV) identified in 2008

Virus % of Cancer Cancer Types
Hepatitis (HBV and HCV) 4.9% Hepatocellular
Human T-lymphotropic
(HTLV)
.03% Adult T cell
leukemia
Human
Papillomavirus (HPV)
5.2% Cervix, Anus,
Vulva, Vagina,
Oropharynx
Kaposi sarcoma
associated herpesvirus
(HHV-8)
0.9% Kaposi sarcoma,
multicentic
Castleman, primary
effusion lymphoma
Merkel cell polyomavirus NA Merkel cell
Epstein-Barr (EBV) NA Burkitt,
nasopharynx
Human Cancer Viruses

Non-HPV = Yellow, HPV =
Oropharynx
HPV
cancers are
primarily
tonsil and
base of the
tongue

Lymphoid Tissue
Tonsils Base of Tongue

Oropharyngeal cancer is the fastest-rising cancer among young white
men in the United States (due to HPV)
Infection with high-risk types of HPV cause nearly all cervical cancers. They
also cause most anal cancers and many oropharyngeal, vaginal, vulvar,
and penile cancers. High-risk HPVs spread easily through direct sexual
contact, including vaginal, oral, and anal sex.
Several vaccines have been developed that prevent infection with the types
of HPV that cause most HPV-associated cancers. In the United States,
experts recommend that children be vaccinated at age 11 or 12, but children
as young as age 9 and adults as old as 26 can also be vaccinated.
Human Papillomaviruses
(HPVs)

www.cdc.gov/std/statistics/2019/default.htm
There were about 43 million HPV
infections in 2018
www.cdc.gov/std/hpv/stdfact-hpv.htm

HPV = Human
Papillomavirus
More than 200 varieties of human papillomavirus (HPV) exist, double-
stranded DNA viruses that infect only humans
HPV is a very common virus; nearly 80 million people—about one in
four—are currently infected in the United States.
Base of the tongue and tonsillar
cancer HPV-16 genotype
causative agent in many, Other
high-risk HPV genotypes, such
as HPV-18, 31, or 33, are also
causative but are less common

PROJECTED NUMBERS OF NEW CASES IN THE FUTURE
J Clin Oncol
2011;29:4294

Having a tonsillectomy as a
child may reduce the risk of
getting tonsil cancer by 60 –
85%
Cancer Prev Res; 2015; 8(7); 583–9
Br J Cancer 2016 Mar 29; 114(7): 832–838

0
1
2
3
4
5
6
7
8
1959 1979 1996
Tonsillectomy Rates in the US (cases
per 1000)
Dramatic decline
in routine
tonsillectomies
since 1959
Still about ½
million done
every year (74
million kids in
the US)

The Impact of Tonsillectomy upon the Risk of Oropharyngeal Carcinoma
Diagnosis and Prognosis in the Danish Cancer Registry
Fakhry Cancer Prev Res; 8(7); 583–9
From 1977 to 2012, the incidence of tonsillectomies significantly
decreased, whereas the incidence of oropharyngeal carcinoma
significantly increased.
77% of tonsil carcinomas diagnosed in Denmark between 2000 and
2010 were HPV-related
The risk of diagnosis with tonsil carcinoma at age <60 years was
significantly decreased by 85% after tonsillectomy.

If you have tonsillectomy before the age of
13 the risk of tonsil cancer goes down by 81%
but the risk of base of tongue cancer goes up
by 246%!
If you delay tonsillectomy to 13 or older the
risk of tonsil cancer is reduced by 68% and
base of tongue is reduced by 67%
Br J Cancer 2016 Mar 29; 114(7): 832–838.) North Carolina
Having tonsillectomy at a young age may cause BOT lymphoid hypertrophy and
lower tonsil cancer but increase base of tongue cancer risk

0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 2020
Men
Women
Declining Smoking in the US
Humphrey Bogart
Dead at 57 from
esophagus cancer in
1957

Latency in Men between
smoking rates and lung cancer
rates
smokin
g lung
cancer
Time interval 20 to 30
years

1920 1940 1960 1980 2000
Year
smoking
H&N cancer
oropharynx
Other H&N
225% Increase in HPV+ vs 50% decrease in HPV -
Lower smoking rates
have lowered the
incidence of smoking
related head and
neck cancers but
virus-related cancers
are sky rocketing

Dramatic Rise in HPV + Tonsil Cancer
Smoking
The timing between exposure to HPV and the development of
oropharyngeal cancer probably exceeds 10 years
HPV Most
Common
HPV +
HPV -

HPV AND OROPHARYNGEAL CANCER
Latency from infection:
Cervix (29 years) peak infection (20y) to cancer (49y)
OPX / HPV (10-30y) peak infection (25-30 and 55-
60) and cancer 61y
HPV Vaccine impact expected by 2050

Latency from Infection to Cancer
20 – 30
years

GARDASIL
The Food and Drug Administration (FDA) has approved three vaccines
that prevent infection with disease-causing HPV
types: Gardasil®, Gardasil® 9, and Cervarix®.
All three vaccines prevent infection with HPV types 16 and 18,
two high-risk HPVs that cause about 70% of cervical cancers and an
even higher percentage of some of the other HPV-caused cancers.
Gardasil also prevents infection with HPV types 6 and 11, which cause
90% of genital warts.
Gardasil 9 prevents infection with the same four HPV types plus five
additional cancer-causing types (31, 33, 45, 52, and 58).
As of May 2017, Gardasil 9 is the only HPV vaccine available for use in
the United States. Cervarix and Gardasil are still used in other

WHAT IS GARDASIL VACCINE (HPV), AND
HOW DOES IT WORK (MECHANISM OF
ACTION)?
Gardasil is a sterile preparation for intramuscular injection and contains purified
inactive proteins from HPV. The proteins in Gardasil are structural, virus-like proteins
(VLP) that resemble the HPV virus. The proteins can activate the immune system but
cannot give rise to replicating virus.
Viral proteins used in Gardasil are manufactured in yeast cells using recombinant
technology. Once released from yeast cells, the VLPs are purified. Once Gardasil is
administered, the body's immune system recognizes the viral proteins in Gardasil as
foreign, and develops antibodies against them, thus providing immunity from future
infections.

Oropharyngeal cancer “is the fastest-
rising cancer among young white men
in the United States,
Routine vaccination against HPV has
been recommended since mid-2006
for 11- to 12-year-old girls and for
females up to age 26 who have not
previously been vaccinated. HPV
vaccination has been recommended for
males ages 9–26 since 2009.
Impact of HPV vaccination on oral HPV infections
among young adults in the U.S.
Presented ASCO June 5, 2017

GARDASIL 9 is a vaccine indicated in females 9 through 45 years of
age for the prevention of cervical, vulvar, vaginal, anal,
oropharyngeal and other head and neck cancers caused by human
papillomavirus (HPV)
indicated in males 9 through 45 years of age for the prevention of
anal, oropharyngeal and other head and neck cancers caused by
HPV

Increase the proportion of adolescents who receive
recommended doses of the human papillomavirus (HPV)
vaccine
Baseline: 48.0 percent of adolescents aged 13 through 15 years
received recommended doses of the HPV vaccine by 2018
Target: 80.0 percent
Target Setting Method
Maintain consistency with national programs, regulations, policies,

Survival for Tonsil
Cancer
HPV +
HPV -
Cure rate for
HPV tonsil
cancer is more
than twice as
good as
smoking
related

1.Viruses cause a significant number of cancers and
in the US HPV most significant
2.Best chance of eliminating this risk is to vaccinate
young people with Gardasil 9
3.SARS-Cov2 virus does not code for any known
oncoprotein so (based on current information)
would not be considered an oncovirus, but the
long-term effects of immune suppression or
chronic inflammation raise concern.

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