Cancer and infectious disease

Definition

Infectious diseases caused by viruses, bacteria, and parasites have been linked to cancer, an uncontrolled growth of cells in the body. Globally, between 15 and 20 percent of cancers are linked to some type of infectious disease. The incidence is less common in developed countries, with approximately 10 percent of cancers linked to an infectious disease. In 2020, 2.3 million global cancer cases were attributed to infections.

Causes

Infection with viruses, bacteria, or parasites stimulates the production of white blood cells and other immune responses, which ultimately cause inflammation. This inflammatory response is necessary to kill the foreign organisms. The substances that white blood cells produce, however, also damage deoxyribonucleic acid (DNA), proteins, and other cells. Also, inflammation causes cells to divide at a faster rate than normal. With chronic infection, inflammation may also become chronic, which suggests continued cell damage that could lead to the development of mutated cells and cancer.

Foreign organisms, particularly viruses, can enter human cells and directly interact with DNA. This interaction can activate genes that promote tumor growth or can inactivate genes that prevent tumors from growing. These organisms may prevent the body from destroying damaged cells. These cells can then continue to grow and may become cancerous through a process called oncogenesis. Some viruses, such as the human immunodeficiency virus (HIV), prevent the immune system from recognizing cancer cells or cells infected with cancer-causing viruses.

An estimated 30 to 40 percent of Americans are infected with Helicobacter pylori at any given time, and it impacts two-thirds of the world’s population. H. pylori is a screw-shaped bacterium that burrows into the stomach lining and causes chronic inflammation and cell proliferation. An estimated 10 to 15 percent of persons infected with H. pylori will develop peptic ulcers (three to four times the rate of individuals without this infection), and around 3 percent will develop stomach cancer. Infection with H. pylori increases the risk of developing stomach cancer eightfold.

There are more than one hundred types of human papillomavirus (HPV). Infection with certain types of these viruses can cause warts or benign tumors called papillomas. Some types of HPV cause common warts on hands and feet, while other types cause warts in the genital area. Most of these infections are self-limited (they resolve without treatment); however, for some persons, infection can last many years and may or may not lead to cancer. HPV can interfere with human proteins that keep tumors from growing, and persistent HPV infection is associated with cervical cancer. Other cancers associated with HPV include cancer of the anus, vulva, vagina, and penis. Over 90 percent of cervical and anal cancers are attributed to HPV infections.

Infection with hepatitis B virus causes inflammation of the liver. Infection is usually acute, lasting no more than six months. Persons who develop the chronic form of hepatitis B, which lasts for more than six months, are at high risk for cirrhosis and liver cancer. Chronic infection with the hepatitis C virus leads to permanent scarring of the liver (referred to as cirrhosis) and, in some persons, liver cancer.

HIV infection is associated with Kaposi’s sarcoma, non-Hodgkin’s lymphoma, cervical cancer, anal cancer, Hodgkin’s lymphoma, liver cancer, and lung cancer. The association between HIV and certain cancers is unclear, however, but it is believed that because the virus severely weakens the body’s immune system, the body is made more susceptible to cancer. Persons infected with HIV are also more likely to be infected with other viruses that increase the risk of certain cancers.

The Epstein-Barr virus (EBV) causes infectious mononucleosis. EBV infection is associated with about one-third of Hodgkin’s lymphoma cases and with developing non-Hodgkin’s lymphoma. EBV is detected in tumors, and the EBV genome (hereditary information) is detected in the cancer cells.

Infections with parasites that cause cancer are more common in underdeveloped and developing countries. Parasites, such as blood flukes, can cause schistosomiasis, which is associated with bladder cancer, and liver flukes can cause an infection with Opisthorchis viverrini, which is associated with cancer of the bile duct and other types of liver cancer.

Risk Factors

H. pylori is acquired by consuming contaminated food or water or by direct oral contact. In many cases, it is first acquired during childhood. Living in crowded, unhealthy conditions and having a lower socioeconomic status (which often precipitates poor living conditions) are risk factors for H. pylori infection.

HPV, HIV, and hepatitis B and C viruses can be spread by sex with an infected partner; by using shared, contaminated hypodermic needles; and by getting an unsterile tattoo, body piercing, or surgical procedure. Having many sexual partners increases the likelihood of acquiring these infections. Having received a blood transfusion before 1992 is also a risk factor for HIV and hepatitis C virus infection. Healthcare workers are at risk of acquiring HIV or hepatitis B or C from patients, and infants are at risk of acquiring any of these viruses from their infected mothers.

Many persons are infected with EBV by the time they reach adulthood. The virus is transmitted by contact with an infected person’s saliva through kissing, coughing, or sneezing. Sharing food or beverages from the container or utensil of an infected person also can transfer the virus. Up to 80 percent of people who develop mononucleosis and recover will continue to secrete EBV in their saliva for a few months or even years.

Symptoms

H. pylori infection is associated with aching or burning pain in the abdomen and with nausea, vomiting, frequent burping, bloating, and weight loss.

HPV infection can occur without symptoms; however, some persons can develop genital warts with an HPV infection. The warts may be raised, flat, pink, or flesh-colored; large or small; or shaped like cauliflower. Single or multiple warts may appear on the anus, cervix, scrotum, groin, thigh, or penis.

Infection with hepatitis B or C virus may be asymptomatic. However, some persons may complain of right upper quadrant abdominal pain, ascites (fluid collection in the abdomen), bleeding varices (dilated veins in the esophagus), dark urine, fatigue, fever, generalized itching, jaundice (yellowing of the skin), anorexia (loss of appetite), nausea, light-colored stools, and vomiting.

When persons first become infected with HIV, many are without symptoms; some get a flu-like illness within three to six weeks of exposure. These persons may complain of fever, headache, tiredness, nausea, diarrhea, and enlarged lymph nodes, which can last one to four weeks. For a period of time, the body’s immune response keeps the virus in check. Eventually, however, the virus load rises to high levels. Over time, the immune system is weakened, and the infected person becomes more susceptible to opportunistic infections and cancer.

Symptoms of infection with EBV include a fever, malaise (feeling very tired), swollen lymph nodes, and a sore throat.

Screening and Diagnosis

Screening and early diagnosis of infection can increase the likelihood of treatment and subsequently reduce the risk of developing an associated cancer. With infections that are asymptomatic, screening and early diagnosis of the cancer may improve the chance of early treatment and cure.

H. pylori testing is routinely done for persons diagnosed with a peptic ulcer. In addition, patients with a family history of stomach cancer should be tested for H. pylori infection. Testing includes a blood test to check for H. pylori antibodies; a urea breath test, which is positive if H. pylori is present; and a stool antigen test, which checks for H. pylori antigens in the person’s stool. A biopsy to check for H. pylori may also be obtained through endoscopy.

The Pap test (or smear) is part of a gynecological exam that checks for changes in the cells of the cervix. A test to check for types of HPV that are high risk for cancer in cervical cells is done as part of the Pap test.

Hepatitis B and C are diagnosed using blood tests that check for virus antibodies and virus levels (also called viral load). In addition, liver function tests, albumin level, and prothrombin time are checked to assess the effects of the virus on the liver.

Two tests are used in combination to check for HIV antibodies and to increase testing accuracy. If antibodies are detected by the ELISA (enzyme-linked immunosorbent assay) method, then a second test using the Western blot procedure confirms the diagnosis. Persons who are diagnosed with a sexually transmitted disease or have other risk factors for acquiring HIV should be tested. Other tests include a viral load and a CD4 count.

Antigens for EBV are done to determine if a person has been infected with the virus. EBV can cause mononucleosis, which is diagnosed when a person has an elevated monocyte (type of white blood cell) count.

Treatment and Therapy

Treatment of infection may prevent cancer from developing, if the infection is cured. In many cases, however, the infection cannot be cured but its severity can be reduced, helping to lessen damage to the immune system and body and reducing the likelihood of developing cancer.

H. pylori infection is treatable. Persons with peptic ulcers caused by H. pylori are treated with antibiotics and medications, such as proton pump inhibitors, histamine 2 receptor blockers, or bismuth subsalicylate, that block the production of stomach acid.

There is no cure for HPV infection; however, the warts that develop with the infection can be treated with cryosurgery (freezing that destroys tissue), loop electrosurgical excision procedure (removal of tissue using a hot wire loop), and conventional surgical removal.

No cure exists for hepatitis B infection, but medications may suppress the virus production and reduce the damage to the liver. No medications exist that can prevent acute hepatitis B from becoming a chronic infection. Acute hepatitis B infection is usually a self-limiting infection and resolves within a few weeks. Hepatitis B immunoglobulin may be given within twenty-four hours of exposure to the virus to protect the person from developing chronic hepatitis B infection. Several medications have been approved by the US Food and Drug Administration for the management of chronic hepatitis B virus infection. These medications include interferon, lamivudine, telbivudine, tenofovir, adefovir, and entecavir.

No cure for hepatitis C infection has been developed, but medications may suppress virus production and reduce damage to the liver. No medications exist that can prevent acute hepatitis C from becoming a chronic infection. Management of hepatitis C infection includes pegylated interferon and ribavirin, which may be given for up to forty-eight weeks.

No cure exists for HIV; however, based on the person’s viral load and CD4 count, antiretroviral treatment is recommended. HIV treatments have dramatically improved since first introduced. Newer, more effective medications and older proven medications can be taken less frequently with reduced adverse effects. Highly active antiretroviral therapy, or HAART, includes a drug combination that targets different aspects of virus replication or growth to control the infection. A paradigm shift is occurring in the treatment of HIV. Many persons now consider HIV to be a chronic disease rather than a progressive, fatal infection.

There is no cure for mononucleosis. Persons infected with EBV may have symptoms for several months, however, the infection is usually self-limiting. In general, antiviral medications are not effective, and supportive care (plenty of oral fluids to prevent dehydration, acetaminophen for fever, and bed rest) is recommended to manage the symptoms of the infection.

Prevention and Outcomes

If infection with the offending organism is prevented, then the associated cancer will likely be avoided. The efficacy of vaccines that prevent chronic infection with these organisms is based on this premise. Minimizing the exposure of infected persons to other persons also can decrease the risk of spreading infections.

One can reduce the spread of viruses, bacteria, and parasites through good handwashing technique and covering the mouth and nose when coughing or sneezing. One should also eat food that has been washed well or cooked properly and should drink water from a clean source. Eating a nutritious diet and exercising regularly also decrease the risk of developing cancer. Routine doctor visits allow early screening and diagnosis, and follow-up on abnormal test results may prevent cancer.

To reduce the risk of infection with HIV or hepatitis B or C virus, persons should avoid contact with blood or blood products whenever possible. Sexual transmission of infectious diseases is low among monogamous couples. Persons should not inject illicit drugs or share needles and should not share razors, toothbrushes, or nail clippers in households with an infected person.

There is no vaccine for the prevention of hepatitis C infection; however, there is a vaccine for hepatitis B. The hepatitis B vaccine should be given to newborns, children who were not previously vaccinated, and adults in high-risk groups. There is no vaccine for the prevention of HIV; however, condom use minimizes the risk of acquiring and spreading HIV.

Avoiding genital contact with another can prevent infection with HPV. For those who choose to be sexually active, a long-term, mutually monogamous relationship with an uninfected partner reduces the risk of infection. However, it is difficult to determine if a partner who has been sexually active in the past is currently infected. HPV infection can occur in both male and female genital areas that are covered or protected by a latex condom, and in areas that are not covered. Vaccines that prevent HPV infection are available.

There is no vaccine to prevent infection with EBV. Avoiding persons infected with the virus is difficult because many who carry the virus do not know they are infected. However, general good hygiene and being cautious if a person’s immune system is suppressed or not functioning properly can help reduce the risk of contracting the infection.

Some research indicates that the presence of multiple viruses, co-infection, can increase the risk of developing an infection-related cancer. Modern technology has aided researchers in identifying new and emerging oncogenic infections. The discovery of these organisms implies the possibility that the cause of some existing cancers may have an infection component.

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