What Is the Most Common Virus That Causes Cancer?
What Is the Most Common Virus That Causes Cancer?
HPV causes more cancers worldwide than any other virus — but it is only one of several infections capable of contributing to human cancer.
Cancer is usually thought of as a disease of damaged genes. But sometimes the chain of events that leads to cancer begins with something entirely different: an infection.
Most familiar viral infections are not associated with cancer. The viruses that cause the common cold, influenza viruses and coronaviruses such as SARS-CoV-2 are not established cancer-causing viruses.
But a small group of viruses can, under the right circumstances and often over many years, contribute to the development of cancer. Among them, HPV is responsible for the largest number of cancer cases worldwide.
According to the International Agency for Research on Cancer (IARC), almost 750,000 new cancer cases worldwide in 2020 were attributable to HPV infection.
HPV is not alone. Hepatitis B and C viruses can cause liver cancer. Epstein–Barr virus is associated with several lymphomas and other cancers. Other viruses are linked to cancers ranging from Kaposi sarcoma to adult T-cell leukaemia.
So how can a virus eventually help turn a normal human cell into a cancer cell? And if some of these infections are extremely common, why do most infected people never develop cancer?
What Does “Cancer-Causing Virus” Actually Mean?
Calling a virus “cancer-causing” does not mean that infection inevitably leads to cancer.
HPV provides a good example. HPV infection is extremely common, yet most infections disappear as the immune system controls them. The problem arises when infection with certain high-risk HPV types persists.
Cancer is therefore rarely an immediate consequence of infection. Instead, infection can begin a biological process that unfolds over many years:
Viral infection → persistent infection → disruption of normal cellular control → additional cellular changes → cancer
Different viruses accomplish this in different ways. Some viral proteins interfere directly with the machinery controlling cell growth and division. Others cause chronic inflammation and repeated tissue damage. Some alter immune responses or help infected cells survive when they normally should not.
Cancer can be the eventual result — sometimes decades after the original infection.
Why Is HPV So Important?
HPV is not one virus but a family of around 200 known types. Most do not cause cancer.
A smaller group known as high-risk HPV can cause cancer when infection persists. Among them, HPV16 and HPV18 are particularly important.
The strongest relationship is with cervical cancer. Persistent high-risk HPV infection causes virtually all cervical cancers.
But HPV does not cause only cervical cancer. It also contributes to anal, oropharyngeal, vaginal, vulvar and penile cancers.
A Personal Note
Early in my research career, I remember asking a simple question: if so many HPV types exist, could we find something they all share and use it to make a universal HPV vaccine?
Of course, the biology is not quite that simple. A sequence being conserved does not necessarily make it a good vaccine target. It also needs to produce an epitope that the immune system can recognise strongly enough to provide protection.
Still, the basic question is an interesting one. Researchers are exploring broadly protective HPV vaccines based on conserved epitopes shared across multiple HPV types, including regions of the L2 capsid protein.
How Can HPV Turn a Normal Cell Towards Cancer?
Two HPV proteins are particularly important: E6 and E7.
These viral proteins interfere with cellular pathways involving two of the best-known tumour suppressors in cancer biology: p53 and retinoblastoma protein (pRb).
Normally, these systems help prevent damaged or abnormal cells from continuing to divide. Persistent infection with high-risk HPV can interfere with those safeguards.
That does not instantly transform an infected cell into a cancer cell. Additional changes are required, but over time abnormal cells can survive and accumulate further genetic and cellular alterations, eventually allowing some to become malignant.
Why Doesn't Everyone With HPV Get Cancer?
HPV infection is common. Cancer is not.
In most people, the immune system controls the infection, usually within a year or two. The greatest risk occurs when infection with a high-risk HPV type persists for years.
Even then, progression to cancer is not inevitable. Viral type, immune control, duration of infection and additional changes within infected cells all influence what happens next.
A better way to think about the process is:
HPV infection is common.
Persistent high-risk HPV infection is less common.
Cancer is a much later and much rarer outcome.
What Other Viruses Can Cause Cancer?
HPV causes the largest number of virus-attributable cancer cases globally, but several other viruses are established causes of human cancer.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) can produce chronic liver infection, inflammation and damage that increase the risk of hepatocellular carcinoma.
Epstein–Barr virus (EBV) infects most people at some point in their lives but is associated with only a small proportion of cancers, including Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma and some gastric cancers.
Human T-cell leukaemia virus type 1 (HTLV-1) can cause adult T-cell leukaemia/lymphoma, sometimes decades after infection.
Kaposi sarcoma-associated herpesvirus (KSHV or HHV-8) is associated with Kaposi sarcoma and certain other rare malignancies, particularly when immune control is impaired.
Merkel cell polyomavirus is associated with most cases of Merkel cell carcinoma, a rare but aggressive skin cancer.
These viruses do not all cause cancer in the same way, but they illustrate the same remarkable principle: an infection can sometimes initiate a biological process that ends, years later, as cancer.
Can a Vaccine Prevent Cancer?
If a virus can cause cancer, then preventing infection with that virus may prevent the cancer before the first malignant cell ever exists.
The hepatitis B vaccine prevents HBV infection and reduces the risk of liver cancer. The HPV vaccine prevents infection with major cancer-causing HPV types.
These vaccines are therefore doing something unusual. Their immediate target is an infectious agent, but one of their long-term outcomes is cancer prevention.
The HPV Vaccine and Virus-Like Particles
Modern HPV vaccines use virus-like particles, or VLPs. These structures resemble the outside of HPV closely enough for the immune system to recognise them, but they do not contain the infectious viral genome.
Research by Jian Zhou, Xiao-Yi Sun, Ian Frazer and colleagues helped demonstrate how HPV capsid proteins could assemble into virus-like particles, contributing to the scientific foundation that helped make HPV vaccination possible.
Zhou lived long enough to see vaccine development reach clinical trials, but died in 1999 at just 42 — seven years before HPV vaccination entered clinical use.
Read Jian Zhou: The Scientist Who Helped Make the HPV Vaccine Possible
What About Viruses We Cannot Yet Vaccinate Against?
The success of HPV and hepatitis B vaccination also reveals what remains to be done.
There is currently no licensed vaccine against several important cancer-associated viruses, including hepatitis C virus and Epstein–Barr virus.
Hepatitis C provides another form of prevention: modern antiviral drugs can cure most infections, reducing the processes that can eventually lead to severe liver disease and cancer.
A vaccine given today might prevent a cancer that otherwise would not appear for another 20, 30 or 40 years. HPV vaccination has already shown that this idea is not theoretical.
The Bigger Picture
Cancer is not one disease, and it does not have one cause. Some cancers emerge through inherited susceptibility, environmental exposures, ageing or the gradual accumulation of mutations. Others can begin with infection.
Among viruses known to cause human cancer, HPV is responsible for the largest number of cancer cases worldwide.
The discovery that viruses can cause cancer also opened the possibility of preventing some cancers by preventing the infection itself. HPV and hepatitis B vaccination have already shown that this can work.
Sometimes, one of the most effective ways to prevent cancer is to prevent a virus.
Landmark Discovery
One of the major breakthroughs came from the work of German virologist Harald zur Hausen, who proposed that particular types of human papillomavirus were responsible for cervical cancer.
Studies in the early 1980s helped identify HPV16 and HPV18 in cervical cancers, establishing a foundation for understanding persistent high-risk HPV infection as a cause of cervical cancer.
In 2008, zur Hausen received half of the Nobel Prize in Physiology or Medicine for his discovery of human papillomaviruses causing cervical cancer.
Representative Landmark Papers
Dürst M, Gissmann L, Ikenberg H, zur Hausen H.
A papillomavirus DNA from a cervical carcinoma and its prevalence in cancer biopsy samples from different geographic regions.
Proceedings of the National Academy of Sciences. 1983;80:3812–3815.
Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H.
A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer.
EMBO Journal. 1984;3:1151–1157.
Continue Reading
- Jian Zhou: The Scientist Who Helped Make the HPV Vaccine Possible — The VLP research that helped open the way to HPV vaccination.
- Peter Doherty and the Theory That Made It All Make Sense — How T cells recognise virus-infected cells.
- How Was Venetoclax Developed? The Australian Story Behind a Breakthrough Cancer Therapy — From fundamental cancer biology to a new treatment.
- Frank Macfarlane Burnet: The Nobel Prize Winner Who Shaped Modern Immunology — The ideas that helped shape modern immunology.
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