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Robert J Miller MD, profile picture
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Viruses and cancer

Certain viruses are linked to increased cancer risk by disrupting cell signaling, weakening the immune system, or causing chronic inflammation. Between 30-50% of cancers are preventable through vaccination or avoiding risk factors. Viruses linked to cancer include HPV (cervical, other anogenital cancers), HBV and HCV (hepatocellular carcinoma), EBV (Burkitt's lymphoma, nasopharyngeal carcinoma), HIV (Kaposi's sarcoma, lymphomas), HTLV-1 (adult T-cell leukemia), KSHV (Kaposi's sarcoma), and MCPyV (Merkel cell carcinoma). Oropharyngeal cancer rates are rising due to HPV transmission during oral

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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
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,
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
HPV TYPES
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 -
Median age 63
Median age 61
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
HPV Immunization 2018
Girls stalled at 49%
Boys up to 47%
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.