Human Papillomavirus

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Human papillomavirus (HPV) is the most prevalent cancer causing virus and is linked to cervical, anal, vulvar, penile, and some oral cancers (Phelps, 2012). HPV is also the most common sexually transmitted disease, and most sexually active people will have it at some point in their life. Currently, 79 million Americans are infected with the HPV virus. Not all forms of HPV are harmful, and many strains will go away on their own (CDC, 2014). It is estimated that 70-90% of HPV strains are eliminated from the body by the immune system (Cleveland Clinic, 2012). HPV is typically spread through sexual contact, whether it be vaginal, anal, or oral sexual intercourse. Someone who is asymtomatic can spread the virus to his or her partner, and it can often take months or years for the onset of symtoms, making it difficult to pinpoint when the virus was contracted (CDC, 2014). Some people develop genital warts from HPV, but many remain asymptomatic and are only diagnosed through routine screenings. Screenings are primarily performed during a pap smear and are recommended only for women over the age of 30. Women under 30 and men are not routinely screened for HPV, so many cases go undiagnosed for long periods of time, which can be fatal if the HPV has caused cancer. There are currently no approved tests to screen for HPV in men or to detect HPV in the anus, vagina, penis, or mouth. (National Cancer Institute, 2011).

How does HPV cause cancer?
HPV accounts for 5% of all cancers worldwide, and virtually all cases of cervical cancer are caused by HPV (National Cancer Institute, 2011). So how does this virus cause cancer? The HPV virus infects epithelial cells, which cover the inside and outside of our skin, throat, genital tract, and anus. Once the HPV virus has infected the epithelial cell, it begins to make proteins. The proteins allow the cell to grow uncontrollably and prevents cell death. When the immune system fails to eliminate these cells, mutations can occur which eventually lead to a tumor. Some researchers believe it can take between 10 and 20 years after being infected with HPV until a tumor forms (National Cancer Institute, 2011).

Prevention:
There are two vaccines that have been approved to prevent HPV: Gardasil and Cervarix. Gardasil is a series of three shots given over a 6 month period that is approved for males and females aged 9 to 26. It protects against four strains of HPV (6, 11, 16, and 18), protect against genital warts, and protects against certain anal and vulvar cancers. Cervarix is also given in three shots over a 6 month period, but is only approved for females between the ages of 9 and 25. It protects against only two strains of HPV (16 and 18) and provides no protection against genital warts or other types of cancer (National Cancer Institute,2011). The best way to prevent HPV besides vaccinations is the use of condoms. Transmission of HPV is primarily through sexual contact, whether it be vaginal, anal, or oral, so condom use can prevent that skin to skin contact and prevent the spread of HPV as well as other STI's (National Cancer Institute, 2011).

Treatment:
There is no way to treat the virus itself, but there are treatments for genital warts and cervical cancer. There are prescription creams that can be applied topically to the warts, as well as various surgeries and treatments. There is cryosurgery which is using liquid nitrogen to freeze off the warts or abnormal cells. Warts can also be removed with heat using electocautery or with light using laser therapy. Abnormal or cancerous cells can be removed with Loop Electrosurgical Excision Procedure (LEEP). LEEP is performed with a specialized wire loop to remove abnormal cells (Cleveland Clinic, 2012).

References

Genital HPV infection-Fact sheet. (2014, March 20). Retrieved from Center for Disease Control and Prevention website: http://www.cdc.gov/std/hpv/stdfact-hpv.htm

Human papillomavirus (HPV) vaccines. (2011, December 29). Retrieved from National Cancer Institute website: http://www.cancer.gov/cancertopics/factsheet/prevention/HPV-vaccine

Phelps, W. (2012, March 4). Viruses, bacteria, and cancer, or it's not all smoke and sunlight. Retrieved from American Cancer Society website: http://www.cancer.org/cancer/news/expertvoices/post/2012/03/04/viruses-bacteria-and-cancer-or-ite28099s-not-all-smoke-and-sunlight.aspx

Understanding cervical HPV. (2012, March 12). Retrieved from Cleveland Clinic website: http://my.clevelandclinic.org/disorders/genital_warts/hic_understanding_hpv.aspx

HPV and Cervical Cancer

Epstein-Barr Virus

The Epstein-Barr Virus (EBV) is part of the herpesvirus family, and like most herpes viruses it has an envelope and causes a latent infection that lasts a lifetime. EBV has a double stranded DNA genome which causes less mutations because it is more stable than RNA. EBV is one of the most common human viruses, and most people get it at some point during their life.It is known that EBV infects over 90% of adults world-wide, and once you are infected with the virus, you are a carrier for life. (Thompson & Kurzrock, 2004). The EBV virus is transmitted through salivary contact such as kissing. It has been attributed to Burkitt's lymphoma, Hodgkin's disease, and nasopharyngeal carcinoma. EBV is the primary cause of infectious mononucleosis, a benign disease that many people have as teens or young adults. It is often shortened to 'mono' and has been dubbed 'the kissing disease (Dolcetti et al., 2014).

How EBV Causes Cancer

In order to cause cancer, EBV must "maintain it's viral genome in the cell, avoid killing the cell, and prevent the cell from becoming a target for destruction from the immune system. Finally the virus must activate cellular growth control pathways," (Thompson & Kurzrock, 2004). The EBV remains latent in the B cells and integrates its DNA into the host genome. In cancer-causing EBV, a gene called EBNA-1 is expressed, and the immune system doesn't detect it, so the cytotoxic T cells don't attack it. The EBV goes through the lyric cycle which suppresses protein synthesis in the host. Cell death then occurs which releases virions to infect more cells. The final step that makes EBV oncogenic is interfering with intracellular signals that control cell growth. This will result in rapid and uncontrolled growth, ultimately resulting in a malignant tumor. (Thompson & Kurzrock, 2004).

Hodgkin's Lymphoma

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It is believed that a history of infectious mononucleosis (caused by the EBV) increases a person's chance to develop Hodgkin's lymphoma. The distinguishing factor between non-Hodgkin's lymphoma and Hodgkin's lymphoma is an abnormal type of cells called Reed-Sternburg cells that are found solely in Hodgkin's lymphoma. Pieces of DNA from the EBV have been found in the Reed-Sternburg cells, suggesting that this virus may be the cause. It is most common in the United States, Europe, and Canada and occurs more commonly among high socioeconomic populations. It is speculated that it occurs among the wealthier populations because they may have been protected from the virus until much later in life than someone with a lower socioeconomic status (American Cancer Society, 2012).

Symptoms of Hodgkin's Lymphoma

• Enlargement of lymph nodes-usually neck, armpit, or groin. Usually not painful!
• Night sweats
• Severe and persistent itching
• Fatigue
• Loss of appetite
• Weight loss
• Fever that comes and goes
• Cough
• Trouble breathing while laying down

(American Cancer Society, 2012). 

Diagnosis of Hodgkin's Lymhoma

Typically, patients will see their doctor when they have a lump on their neck, armpit, or groin that won't go away. The first step in diagnosing Hodgkin's is performing a biopsy. If the lymph node is near the surface of the skin, a local anesthetic is used to numb the skin while a small portion or the whole lymph node is removed for testing. If the lymph node is in the chest, the patient will be put under general anesthesia to have the biopsy done. Normally, a diagnosis can be made by examining the tissue underneath a microscope. Immunohistochemistry may be performed to confirm the diagnosis.  With this test, a stain is used to identify surface proteins that are unique to Hodgkin's Lymphoma (American Cancer Society, 2012). 

Treatment of Hodgkin's Lymphoma

• Chemotherapy
• Radiation 
• Stem cell transplant
• Injecting antibodies that identify the surface proteins on Hodgkin's cells

(American Cancer Society, 2012).

Burkitt's Lymphoma

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Burkitt's Lymphoma is a type of Non-Hodgkin's lymphoma. It is a rare type of B-cell lymphoma. There are only about 300 new cases per year in the United States.  Burkitt's lymphoma is more common in children and is found mainly in Africa, but there are sporadic cases world-wide. It is linked to the EBV, but not all patients with Burkitt's lymphoma have EBV. Endemic Burkitt's lymphoma only affects children who have had malaria, and it is believed that malaria lowers the resistance to the EBV. One of the distinctive features of endemic Burkitt's lymhoma is cancerous growths in the jawbone or other facial bones. Sporadic Burkitt's lymphoma, also called non-African Burkitt's lymphoma, is also tied to EBV but presents slightly differently. Sporadic Burkitt's lymphoma tends to affect the ileo-cecal region more than the jawbone. (Canadian Cancer Society, n.d).

Symptoms of Burkitt's Lymphoma

• Lymph nodes growing together
• Nodes that aren't tender
• Swollen nodes in abdomen or chest
• Abdominal pain
• Nausea and vomiting
• Diarrhea 
• Bowel obstruction
• Weight loss
• Fever
• Night sweats

(Lymphoma Association, 2012)

Diagnosis

Diagnosis is made by a biopsy of the tissue that is affected. CT scans, ultrasounds, X-rays, and bone marrow biopsies are used to determine the stage of the cancer. 

Stage I-One area outside of the lymph nodes are affected or one area of lymph nodes outside of the chest is affected. 

Stage II-There is a tumor outside of the lymph nodes and nearby nodes are affected. 

Stage III- There are tumors on both sides of the diaphragm. 

Stage IV- The cancer has spread to the bone marrow or spinal cord.

(Stanford School of Medicine, 2001)

Treatment

• Chemotherapy
• Rituximab- a form of antibody therapy that targets a surface protein on B-lymphoma cells

(Lymphoma Association, 2012)

Nasopharyngeal Carcinoma

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Nasopharyngeal cancer starts in the back of the throat, behind the nose. All types of nasopharyngeal cancer start in the epithelial cells that line the surface of our body. This type of cancer isn't very prevalent in the United States, but occurs more commonly in China. The EBV is linked to nasopharyngeal cancer because parts of the EBV is found in almost all cancerous nasopharyngeal cells. Most patients with this type of cancer also have traces of the EBV in their blood as well (American Cancer Society, 2013). 

Symptoms of Nasopharyngeal Carcinoma

• Lump in neck
• Headache
• Facial pain
• Double vision
• Chronic ear infections
• Nose bleeds
• Hearing loss
• Ringing in the ears
• Numbness in the face
• Nasal blockages or stuffiness
• Trouble opening mouth

(American Cancer Society, 2013).

Diagnosis of Nasopharyngeal Carcinoma

Typically, patients will consult their doctor about a lump in their neck. The doctor will perform a nasopharyngoscopy by either placing a scope through the nose or a small light with mirrors down the throat to inspect the nasopharynx. Not all tumors are visible with a physical exam, so a CT scan may be necessary. A biopsy is taken of the abnormal cells and they are examined underneath a microscope (American Cancer Society, 2013). 

Treatment

• Chemotherapy
• Radiation
• Surgery
• Monoclonal antibodies- man-made antibodies that target a surface protein that signals growth

(American Cancer Society, 2013)

References

Burkitt lymphoma. (2001). Retrieved from Stanford School of Medicine website: http://surgpathcriteria.stanford.edu/bcell/burkitt/grading.html

Burkitt lymphoma. (2012, November 9). Retrieved from Lymphoma Association website: http://www.lymphomas.org.uk/sites/default/files/pdfs/Burkitt-lymphoma.pdf

Burkitt’s lymphoma. (n.d.). Retrieved from Canadian Cancer Society website: http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/pathology-and-staging/types-of-nhl/burkitt-s-lymphoma/?region=on

Dolcetti, R., Guenco, S., Dal Col, J., Celeghin, A., Mastorci, K., & De Rossi, A. (2014). Epstein-Barr virus and telomerase: from cell immortalization  to therapy. Infectious Agents and Cancer, 9(8).

Hodgkin disease. (2012, December 10). Retrieved from American Cancer Society website: http://www.cancer.org/cancer/hodgkindisease/detailedguide/hodgkin-disease-treating-general-info

Nasopharyngeal cancer. (2013, September 23). Retrieved from American Cancer Society website: http://www.cancer.org/cancer/nasopharyngealcancer/detailedguide/nasopharyngeal-cancer-treating-general-info