Human Papillomavirus

 

By: Sheryl Roxas

 

 

Disease Etiology:

Human Papillomavirus (pap-ah-LO-mah-vye-rus) [4] is a virus that belongs to the papova family and papovavirida genera. [7, 8] Usually they cause warts (papillomas) which are non-cancerous. There are over 100 types of HPV and over 60 cause warts on non-genital skin (common warts) and the other 40 are referred to as mucosal, genital type because they thrive only in squamous epithelial cells in the body. Furthermore, these 40 types are divided into two categories of high risk or low risk types. HPV 6 and 11 most often cause genital warts (condyloma acuminata) which are non cancerous so they are low risk types. On the other hand, the high risk types, like HPV 16 and 18 have been linked to cancer of the vulva, vagina, cervix, anus and penis. [2] For the most part, most HPV infections do not pose any real harm, even if infected by multiple types. [3, 4, 5]

 

Disease Transmission:

HPV is passed by infected humans through oral, vaginal or anal sex. [1, 3, 4, 5] Even if the infected person has no sign or symptoms, it can still be passed on to other sex partners and it is possible to acquire more than one type of HPV. [1, 3, 5] Sometimes, a pregnant woman with genital HPV can pass it to her baby upon delivery, in which the child can develop Juvenile Onset Recurrent Respiratory Papillomatosis (JORRP). [1, 3, 4, 5]

 

Reservoirs:

Humans are the reservoirs for Human Papillomavirus. [1, 3, 4, 5]

 

Specific Microbial Characteristics:

HPV belongs to the papova family [7] and papovavirida genera. They are small, circular, double stranded DNA viruses that use overlapping genes and “one strand of DNA to pack the maximum amount of genetic material in a small amount of space”. HPV has two capsid proteins and is non-enveloped with a diameter that is approximately 52-55 nm and “is the only icosohedrally symmetric virion that has skew symmetry”. [8]

 

Specific Tests for Identification:

There are no routine screening tests for HPV- associated diseases except for cervical cancer, which is the easiest female cancer to prevent. There are two tests that can prevent or detect cervical cancer. The pap test also known as pap smear is a test where they take a swab of the cervix and check for cell changes that may become cancerous. The HPV test on the other hand checks for the virus itself and is used with the pap in women 30 and older, especially if the pap has unclear results. [1, 3, 4, 5] The HPV test, like the pap, takes a sample of cervical cells, which is then hybridized with a “specific HPV RNA probe cocktail”. They are then placed on a microplate well coated with antibodies specific for the RNA: DNA hybrids. Alkaline phosphatase reacts with the RNA: DNA hybrids and they are detected with the use of chemiluminescent substrate. When alkaline phosphatase molecules attach to each antibody and the antibodies bind to the hybrids, substantial signal is amplified as a result. Now, as the substrate is torn away from the alkaline phosphatase, light is emitted that is measured as relative light units (RLU) on a luminometer. The intensity of the light signals the presence of the high-risk HPV DNA. If the RLU is equal to or higher that the cutoff value then that indicates the presence of HPV. If the RLU is less than the cutoff value, then HPV is not present or the DNA levels are too low for the test to sufficiently detect it. Regardless the results, keep in mind that the HPV test can only detect the presence of high-risk HPV but not the specific type. [10]

 

Signs and Symptoms:

Most people who have HPV do not develop any symptoms and in about 90% of them, the body clears HPV naturally within two years. Warts (nipple-like protrusions) are a sign that you have HPV.[7] If you develop them around your genitals they are called genital warts but if they are in the throat, which rarely occurs, they are referred to as recurrent respiratory papillomatosis (RRP).[1]

-Genital warts appear as a small bump or a group of bumps on the genital region which left untreated can go away, remain unchanged or actually increase in size and number. Fortunately, the strain of HPV that causes warts never turn into cancer. [4]

-Juvenile Onset Recurrent Respiratory Papillomatosis occurs when a pregnant woman has genital warts and upon delivery of her child passes it onto her baby. The child develops warts in the throat, blocking the breathing passage way, potentially becomes a life threatening condition. [1]

-Cervical cancer is usually asymptomatic until its late stages and then it is harder to treat. That is why screening is important because you can catch before it turns into cancer.

-Cancer of the vulva, vagina, anus head and neck (tongue, tonsil and throat) are less common and might also not present any symptoms until it has advanced. [4]

-Penile cancer is like the other cancers mentioned above but it is the rarest to occur. [1]

 

Historical Information:

The first time HPV was discovered was back in 1956 by a group of scientists. It was in 1984, when Harald zur Hausen discovered, cloned, and attributed cervical cancer to HPV 16 and 18.Throug his research, he has contributed to the production of the vaccines [6]. HPV gets its name because certain strain causes warts, also known as papillomas [4].

 

Virulence Factors:

HPV is a virus that thrives and flourishes on squamous epithelial cells [5], so they can cause different clinical manifestations ranging from asymptomatic infections to life threatening cancer [2]. Genes E1-E8 coded on the Watson, are called the early genes. Genes L1-2, coded on Crick, is called the late genes and they have the code for the major and minor capsid protein after the early genes have coded and replication has taken place. Cancer is supposedly caused after proteins E6 and E7 (produced after the HPV DNA is integrated with the host genome) each bind and destroy a tumor suppressor gene. E6 alters p53 (a gene responsible for stopping the cell cycle to repair the damaged DNA) which causes the altered DNA to keep replicating continuously, resulting in a mutation rate increase. E7 alters retinoblastoma (a gene that keeps a cell from rapid growth) which increases cell response to growth stimulators. In result of the loss of these two inhibitory mechanisms, malignant transformation occurs, hence cancer. [8]

 

Control/Treatment:

Once infected, there is no cure for HPV itself; there are treatments for the problems they can cause. Warts can be left alone to see if they disappear on their own or they can be frozen, cut off, lasered or medicated. The downfall is that they can always come back since you can not cure HPV. Recurrent respiratory papillomatosis can be treated with surgery or medication. Cervical cancer and other HPV related cancers are most treatable when diagnosed early, so early detection is the key. [1, 3, 4, 5]

 

Prevention/Vaccines:

The best way of not ever getting HPV is abstinence. If that is not possible, then be at least in a monogamous relationship with someone who has no or few sex partners. It is also wise to use a condom, even though it is not known how much they protect against HPV. Another way to steer clear from HPV is to get vaccinated.Cervarix and Gardasil can protect against cervical cancer, while Gardasil can also protect against most genital warts. It is recommended for 11 or year old girls, but can be as young as 9 years of age and 13-26 year old women who did not get any or all three recommended doses when they were younger. As for males, Gardasil protects them from most genital warts and is available for 9-26 year olds. It is most effective and beneficial if all three doses of the same brand of vaccine are taken before becoming sexually active. [1, 3, 4, 5]

 

Local cases/outbreaks:

About 20 million people in the US are already infected with the HPV virus and there is still approximately 6.2 million new cases being reported each year. 1% sexually active people in the US between the ages 15-49 years are estimated to have genital warts. HPV infection is the highest among college students that are a minority in race, who consume alcohol and have multiple partners [1].

 

Global cases/outbreaks:

Worldwide, HPV is the most common viral sexually transmitted disease [2]. 20-46% of young women are infected with HPV [1]. Each year there are about 500,000 new cases being reported and about 250,000 deaths occur due to cervical cancer. Attributable to lack of resources, 80% of cervical cancer deaths are prevalent in third world countries. [9]

 

Reference:

1. National Institute of Allergy and Infectious Disease. Human Papillomavirus (HPV) and Genital Warts. Updated 8/13/09. http://www3.niaid.nih.gov/topics/genitalWarts/ 2/19/10

 

2. Microbiology and Immunology Online. Infectious Disease-Chapter 8-Sexually Transmitted Disease. Updated 5/5/09. http://pathmicro.med.sc.edu/Infectious%20Disease/Sexually%20Transmitted%20Diseases.htm 2/19/10

 

3. Texas Department of Health Services. Human Papillomavirus (HPV). Updated 9/27/08. http://www.dshs.state.tx.us/hivstd/info/hpv/default.shtm 2/19/10

 

4. Center for Disease Control and Prevention. HPV. Updated 2/23/10. http://www.cdc.gov/hpv/ 2/22/10

 

5. American Cancer Society. Human Papillomavirus (HPV), Cancer, and HPV Vaccines-Frequently Asked Questions. Updated 10/28/09. http://www.cancer.org/docroot/CRI/content/CRI_2_6x_FAQ_HPV_Vaccines.asp 2/19/10

 

6. Les Prix Canada Gairdner Awards. Harald zur Hausen. Updated 2008. http://www.gairdner.org/awards/awardees2/2008/2008awarde/haraldzurh 2/22/10

 

7. All the Virology on the WWW. Virology Glossary. Created 1995. http://www.virology.net/ATVGlossary.html#h 2/19/10

 

8. Chrissy Oyster and Jamila Johnson. Papovavirus Family. Updated 1/20/99. http://virus.stanford.edu/papova/papovavirus.html. 2/19/10.

 

9. World Health Organization. Human Papillomavirus (HPV). Updated Nov 2009. http://www.who.int/immunization/topics/hpv/en/. 3/7/10.

 

10. Qiagen. The digene HPV Test. Created 2003. http://www.thehpvtest.com/default.html. 3/7/10.