Human Papillomavirus (HPV)
by Chelsea Galinski
Disease: Human Papillomavirus (HPV)
Etiologic agent: The human papillomavirus, a member of the family Papillomaviridae, is the etiologic agent that causes Human Papillomavirus infections that affect skin and mucous membranes. This group of viruses includes more than 100 different strains or types and more than 30 of these viruses are sexually transmitted (1).
Transmission: The transmission of HPV usually occurs through direct skin-to-skin contact, most commonly during anal and vaginal intercourse. Because of this, HPV is easily spread between sexual partners and poses a serious concern for health and safety. HPV is one of the most common sexually transmitted diseases (STD), and since HPV is usually asymptomatic, most individuals are not aware that transmission of HPV has occurred. Occasionally, HPV is transmitted from a pregnant mother to her baby during a normal vaginal delivery, but this is very unlikely (2). Although controversial, there have been studies that have shown non-sexual transmission of HPV is possible and may even occur just by shaking hands with someone who has genitlal warts. Genital HPV infections transmitted by seat surfaces or floors in various public settings has been concluded highly improbable (3).
Reservoirs:Humans are the only known reservoir for HPV (5). As mentioned earlier, HPV affects skin and mucous membranes and it is these membranes and infected skin areas that serve as the main reservoirs for HPV infection, which is why HPV is usually contracted through direct skin-to-skin or genital-to-genital contact (2). Also mentioned previously, the virus may be present on the skin of individuals who have genital warts and may also serve as a reservoir (3). There have also been experimental results that prove the male urogenital tract serves as a reservoir of HPV infection (4).
General characteristics of HPV:HPV can infect the genital areas of both women and men and is a virus specific to humans. This includes the vulva in women, the cervix, the anus, and the linings of the vagina and rectum. In men it is commonly known to infect the skin of the penis and/or the anus (1).
HPV is a virus that very commonly causes genital warts ("low-risk" HPV). HPV is the leading risk factor associated with cancer of the uterus and cervix ("high-risk" HPV), although most people with genital warts caused by HPV never develop cancer of the uterus or cervix (5).
Human Papillomavirus is a member of the Papillomaviridae family and its virions (the form taken by a virus when it is outside living cells and capable of causing infection) consist of a capsid. The virus capsid is not enveloped, and is round with icosahedral symmetry. The diameter of the capsid is around 40 to 55 nanometers. When viewing the virus, the capsomere (protein units that make up the outer coat of the capsid) arrangement is clearly seen (6).
Members of the Papillomaviridae family have a genome that consists of single molecule of super coiled, circular, double-stranded DNA and the genome consists of anywhere from 5300 to 8000 nucleotides. Within this genome, the virus encodes both structural and non-structural proteins and its virions consist of three of these structural proteins (6).
Key tests for identification:Since HPV infects both men and women, how doctors identify HPV infections vary depending on sex. In women, yearly Pap tests are administered which collect cells from the cervix to be tested for signs of abnormal change. An HPV infection is based on the detection of capsid protein or of specific viral nucleic acid (1). The Pap test can detect common "high" and "low-risk" HPV genotypes. There are more specific methods that can be performed by specialized doctors to determine which type of HPV is present if the test is positive for "high-risk" such as a colposcopy or an HPV test. These tests are normally done if your second Pap test still shows signs of abnormal cells (7). More recently, a "hybrid-capture" test known simply as an HPV test was marketed by Digene, and is now used in junction with Pap testing for all women 30 years of age and older, the group considered most at risk of cervical cancer (8). Genital warts are diagnosed by visual inspection of doctors. The use of acetic acid may help identify flat warts, which may often be misdiagnosed because the test is not sensitive specifically to HPV-induced genital warts (1).
In men, genital warts are diagnosed the same way as women. There is currently no FDA-approved test to diagnose HPV or the related cancers it may cause in men. It should be noted that HPV-related cancers are especially rare in men (1).
Signs and symptoms of the disease:There are over 100 kinds of HPV and not all of these different kinds can cause health problems. Some kinds of HPV cause cervical cancer or cancer of the vagina or vulva. These various types of cancer present no signs or symptoms.
Other kinds of HPV can cause genital warts, which favor moist genital surfaces such as the entrance of the vagina and rectum in women. Genital warts can appear to be "small, flat, flesh-colored bumps or tiny, cauliflower-like bumps. (5)" In some cases, genital warts may be too small to see and will need to be further examined. The symptoms of genital warts can include itching, tenderness, burning, pain, or may not even present symptoms at all (5). Genital warts may appear within weeks or months after having sexual contact with an infected person, or may not appear at all. Genital warts are most commonly found on the vulva, in or around the anus or vagina, on the cervix, the penis, thigh, groin, or scrotum (1).
Historical information:Papillomaviruses, the family to which HPV belongs to, were first isolated from rabbits by Richard Shope in 1933. The viral nature of human warts was first identified in 1907. This was the first human virus discovered! It was then shown that these warts, also known as papillomas, could be transmitted from one individual to the next by passing through a filter that catches bacteria (9). The first tumor-inducing virus was discovered in 1911 (11). In 1935, Francis Peyton Rous demonstrated that a Papillomavirus could cause skin cancer in rabbits that were infected. This demonstration showed that viruses can cause cancer in mammals (10). In the early 1970s, Harald zur Hausen was convinced that the skin wart virus, human papilloma, was implicated in cervical cancer and pioneered research on this very subject (11). Zur Hausen was finally accredited with his discovery that human papillomaviruses cause cervical cancer by winning the Nobel Prize in 2008 in Medicine (12). Much of our knowledge about the Human Papillomavirus is accredited to work from the Bovine Papillomavirus (9).
Virulence factors:The virulence factors include proteins E6 and E7 of high-risk serotypes of HPV. These proteins have been shown to inactivate the host's tumor suppressor proteins p53 and Rb. This inactivation of tumor suppresser proteins results in the host cells dividing at rate that cannot be regulated and malignant (cancerous) transformation of these cells. (13)
Control/Treatment:Once an individual contracts HPV, there is no treatment for the actual virus, but those who have a good immune system will usually fight off HPV on their own (14). Genital warts associated with low-risk HPV types have many different treatment options depending on the location and size of the warts. If the warts are small, a doctor may prescribe a medication in the form of a cream to apply to the warts. Other methods to treat genital warts include cryotherapy (freezing the warts with liquid nitrogen), laser treatment, alpha-interferon injections, or surgical removal. Removal of the warts may not be 100% effective because the viral infection may still be present in the underlying tissue (5).
In cases of high-risk HPV types, most commonly found in women, there are also various treatment plans if there are abnormal changes in the cells of the tested area. Sometimes the best treatment is to just observe and wait to see if the abnormal, or "precancerous cell changes," will heal on their own. Other treatment plans include cryotherapy (freezing the abnormal cells with liquid nitrogen), conization (removal of abnormal areas), or LEEP (Loop Electrosurgical Excision Procedure) to remove the abnormal cells with an electrical current that is painless (14).
Prevention/Vaccine info/New trials:To prevent contracting HPV, the most effective way is to avoid having sex with an infected person. If your sexual partner is infected with HPV, condoms may reduce the risk of contracting HPV. Condoms are not always effective, though, because sometimes they do not cover the entire infected area. Risk factors that enhance your chance of contracting HPV also include having multiple sexual partners, the presence of other STDs, poor hygiene, poor nutrition, smoking, and other conditions that might suppress the immune system (5).
More recently, there is a new HPV vaccine, Gardasil, which is recommended for girls that are 11 and 12 years old. It is also recommended to girls and women from ages 13 to 26 who have not received the vaccine earlier. The vaccine was developed to prevent cervical cancer, precancerous genital lesions, and genital warts due to HPV. The vaccine is given in three shots over a six-month period and protects against four types of HPV that are known to cause cervical cancer. It is important to get the vaccine on the proper dates; after the first dose, you should get the second dose at two months and the third dose at six months. According to the FDA, Gardasil is safe and effective and show no serious side effects. The mild side effects that may occur include soreness around the injection site and redness (15).
There is another HPV vaccine in the works, but is not yet licensed, that would prevent women from the two types of HPV that cause the most cervical cancers (15).
Local cases or outbreaks (with incidence figures):
-An estimated 8 out of 10 women will become infected with HPV in their lifetime.
-12,000 people ages 15 to 24 are infected with HPV EVERY DAY in the United States!
-Every day, 30 women are diagnosed with cervical cancer linked to HPV.
-About 60% of female students will become infected with HPV during their 4 years in college.
(All facts above attributed to reference 16)
-An estimated 20 million people in the United States have genital HPV infections at any given time.
-Every year, about 5.5 million people contract a genital HPV infection.
-Although less data is available on HPV statistics among men, levels of current infection in men appear to be similar to those in women.
(All facts above attributed to reference 17)
Global cases or outbreaks (with incidence figures):
-The worldwide prevalence of HPV in cervical cancer is 95-99.7% and in anal cancer is 88%.
1. Centers for Disease Control and Prevention. "Genital HPV Infection - CDC Fact Sheet." 04/10/08. URL: http://www.cdc.gov/std/HPV/STDFact-HPV.htm accessed on 12/2/08.
2. Schoenstadt, Arthur MD. "HPV Transmission." 10/22/07. URL: http://hpv.emedtv.com/hpv/hpv-transmission.html accessed on 12/2/08.
3. Moore, Donnica MD. "Non-sexual HPV Transmission." 05/16/03. URL: http://www.drdonnica.com/faqs/00006368.htm accessed on 12/2/08.
4. Svec, Alexandr, Mikyskova, Iva, Hes, Ondrej, Tachezy, Ruth. Archives of Pathology & Laboratory Medicine. "Human papillomavirus infection of the epididymis and ductus deferens: An evaluation by nested polymerase chain reaction." 11/03. URL: http://findarticles.com/p/articles/mi_qa3725/is_200311/ai_n9340083 accessed on 12/2/08.
5. Johns Hopkins Health Information Service. "Genital Warts." 01/9/07. URL: http://www.hopkinsmedicine.org/Health_Information_Library/?ArticleID=19275 accessed on 12/7/08.
6. ICTVdB - The Universal Virus Database, version 4. "00.099. Papillomaviridae." 2002. URL: http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/ accessed on 12/7/08.
7. Rutgers Health Services. "Colposcopy." 12/22/2005. URL: http://health.rutgers.edu/Gyn/colposcopy.htm accessed on 12/7/08.
8. Digene Corp. "HPV Test vs the Pap FAQs." 2008. URL: http://www.thehpvtest.com/About-the-digene-HPV-Test/HPV-Test-vs-the-Pap-FAQs/Under-30.html accessed on 12/7/08.
9. Microbiology Bytes: Virology. "Papillomaviruses." 09/11/2007. URL: http://www.microbiologybytes.com/virology/Papillomaviruses.html accessed on 12/7/08.
10. The History Channel website. "ROUS, (Francis) Peyton." 2008. URL: http://www.history.com/encyclopedia.do?articleId=221009 accessed on 12/7/08.
11. McIntyre, Peter. "Finding the viral link: the story of Harald zur Hausen." 2005. URL: http://www.cancerworld.org/CancerWorld/getStaticModFile.aspx?id=717 accessed on 12/7/08.
12. The Official Web Site of the Nobel Foundation. "The Nobel Prize in Physiology or Medicine 2008." 2008. URL: http://nobelprize.org/nobel_prizes/medicine/laureates/2008/ accessed on 12/7/08.
13. Gearhart, Peter MD. "Human Papillomavirus." 01/19/08. URL: http://www.emedicine.com/med/TOPIC1037.HTM accessed on 12/7/08.
14. WebMD Medical Reference. "HPV Treatment: Is There an HPV Cure?" 2005-2008. URL: http://www.webmd.com/sexual-conditions/hpv-genital-warts/hpv-treatment-is-there-hpv-cure accessed on 12/7/08.
15.National Center for Immunization and Respiratory Diseases. "HPV Vaccine-Question and Answers." 01/11/08. URL: http://www.cdc.gov/vaccines/vpd-vac/hpv/vac-faqs.htm accessed on 12/7/08.
16. Merck & CO., INC. "Get the Facts about HPV & Cervical Cancer." 06/22/07. URL: http://www.hpv.com/index.html?WT.mc_id=GR06L accessed on 12/7/08.
17. Center for Disease Control and Prevention. "Tracking the Hidden Epidemic: Trends in STDs in the United States." 04/6/01. URL: http://www.cdc.gov/std/Trends2000/hpv.htm accessed on 12/7/08.