Human papillomavirus (HPV)

By Diana Woodworth

Disease: Human papillomavirus (HPV)

Etiologic agent: The human papillomavirus, is a member of the Papillomaviridae family. This family consists of small, non-enveloped DNA viruses comprised of multiple genera (1). Papillomavirus obtained its name from the papillomas, or warts, they cause on epithelium of the body.  There are over 100 identified types of HPV that are associated with causing: genital warts, cervical cancer, anogenital cancers, oral cavity and pharyngeal cancers, and cancer of the vulva, vagina, penis and anus (3).

Transmission: HPV is transmitted, most commonly, during vaginal and anal intercourse.  The virus may also be passed on through genital-to-genital contact and oral sex. The infected partner can spread the virus even if he/she is not showing signs or symptoms of infection (2).

On rare occasions, babies may contract the HPV from their genitally infected mothers during delivery. When this occurs, warts will grow in the throat of the infected child. This condition is called Recurrent Respiratory Papillomatosis (RRP) or juvenile-onset Recurrent Respiratory Papillomatosis (JORRP) (3).

Reservoirs: Humans are the only known natural reservoir of HPV. However, the papillomavirus family is known to affect other species, especially cows and rabbits (3).

Specific tests for identification: Generally, HPV infections of the genitals are first detected through abnormal cell changes in a pap smear. Pap smears are used to screen for cervical cancers and causes of cervical cancer. If a pap smear detects abnormal cell changes, then follow-up DNA testing is preformed. There are several DNA tests that distinguish between sub-types of HPV or detect for “high-risk” HPV stains. If a DNA test is returned as positive, there are high-risk strains of HPV present in the cervix. These specific subtypes include: 16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, 66, 68, and 73 (5).

The only DNA test currently approved by the FDA is the Digene Hybrid Capture 2® (hc2) High-Risk HPV DNA Test. This test detects 13 strains of HPV, but results do not reveal the specific strain present. Instead, results come back as simply positive or negative. This test is approved for women with equivocal pap smear results who are 30 years of age or older (3).

Specific characteristics: Human papillomavirus is a small, double-stranded DNA virus that is non-enveloped(6). The virus infects the epithelial lining of the anogenital tract as well as other cutaneous mucosal tissues (3).  According to the CDC, “the genetic sequence of the outer capsid protein L1”, differentiates the more than 100 strains of HPV (3).

Signs and symptoms: In most cases, HPV infections are asymptomatic and clear themselves within two years of initial infection (NCBI).  Clinical expressions of HPV infection include: genital and anal warts, recurrent respiratory papilloma­tosis, cervical intraepithelial neoplasia, and cancers of the cervix, anus, vagina, vulva, penis, oral cavity, and pharynges (3).

There are approximately 40 strains of HPV that infect mucosal epithelium. These 40 types are classified as “low-risk” and “high-risk” by their epidemiologic association with cervical cancer (CDC). Low-risk, HPV infection, including types 6 and 11, are non-oncogenic. They may cause benign or low-grade cervical cell abnormalities, laryngeal papillomas, and genital warts. High-risk HPV types, including 16 and 18, usually develop into cervical and anogenital cancers and are termed oncogenic (3).

Historical information: The family papillomavirus was first isolated in rabbits in 1933. This discovery was made by Richard Schope, who made the connection between viruses and cancer (7). Another famous scientist, who worked with the papillomavirus family, was Harald zur Hausen. Hausen discovered that cervical cancer was caused by HPV. He was also credited with successfully isolating and characterizing the two most prevalent forms of HPV associated with cervical cancer and developing a preventative vaccine for HPV-related carcinogenesis. Hausen was awarded with a Nobel Prize for Medicine or Physiology for his research in 2008 (8).

Virulence factors: While most infections with HPV resolve themselves with time, more serious infections can become precursor lesions to cervical cancer and eventually the cancer itself. Cervical intraepithelial neoplasia, or CIN, is the most common form of clinically significant genital HPV. Within a few years of infection with HPV CNI-1, or low-level CIN, can develop. CNI-1 may either clear with time or advance into a higher level CIN. CIN-2 and CIN-3 are high-level CINs that are considered pre-cancerous.  While some high-grade CINs regress on their own, more often they will advance into cervical cancer (3).

Research shows that oncogenic HPV strains produce a protein called E6 which targets MAGI-1 at membrane sites and within the nucleus. As E6 degrades MAG-1, tight-junctions lose their integrity in the cell. It is thought that the E6 protein affinity for MAG-1 may contribute to the malignancy of HPV (9).

Control and Treatment: Although genital warts caused by HPV usually disappear on their own, genital wart treatments do exist. Depending on the location and size of the warts, there are several options for topical medication, including: Imiquimod cream, 20 percent podophyllin antimitotic solution, 0.5 percent podofilox solution, 5 percent 5-fluorouracil cream, Trichloroacetic acid (TCA) (10). Small warts may also be removed by, freezing (cryosurgery), burning (electrocautery), or laser treatment. More persistant warts may also be directly injected with alpha interferon, an antiviral medication (10).

Although these medications are used to treat warts, they are not used to treat the virus. At this time, there is no treatment or cure for human papillomavirus (10).

Prevention and Vaccines: The only guaranteed prevention for HPV is abstinence. Other factors that reduce chances of contracting HPV include: limiting your number of sexual partners, choosing partners with little to no other sexual partners, and using a condom during intercourse (11).

There are currently two vaccines that protect against HPV: Gardasil and Cerverix. Gardasil is a recombinant vaccine, approved for females ages 9 to 26, that prevents diseases associated with HPV types 6, 11, 16, and 18. This vaccine is also approved for males ages 9 to 26 to prevent against HPV types 6 and 11, which cause genital warts. Cerverix is a recombinant vaccine, approved for females age 9 to 25, that prevents disease from HPV strains 16 and 18 (11).

Current outbreaks (nationally): Today, roughly 20 million Americans are infected with HPV. Each year, an additional 6 million Americans become infected with the virus. This means that one in two sexually active males and females will contract HPV at some point in their lifetime (12). 12,000 women will be diagnosed with cervical cancer, in the United States, this year and 1% of sexually active Americans will contract genital warts at some point in their lifetime. Populations with higher risk of contracting HPV-related diseases are those with weakened immune systems and gay or bisexual men (12).

Current outbreaks (globally): Internationally, cervical cancer is the second most common cancer among women. In 2008, there were estimated to be 529,409 new cases of cervical cancer, 86% of these cases coming from developing countries. The most common type of cervical cancer worldwide is squamous cell carcinoma, with adenocarcinomas being less common (13).

References:

(1)National Center for Biotechnology Information. “Papillomaviridae.”2002.  http://www.ncbi.nlm.nih.gov/sites/entrez?Db=mesh&term=Papillomaviridae accessed 2-24-12.
 

(2)Centers for Disease Control and Prevention. “What is HPV?” 9-21-11. http://www.cdc.gov/hpv/WhatIsHPV.html accessed 2-26-12.

(3)Centers for Disease Control and Prevention. “Human Papillomavirus.” 2010. http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/hpv.pdf accessed 2-24-12.

(4)Macnab, Joan C. M. and Onions, David. National Center for Biotechnology Information. “Tumor Viruses.” 1996. http://www.ncbi.nlm.nih.gov/books/NBK7998/#A2524 accessed 2-26-12.

(5)Lab Tests Online. “HPV.” 11-17-11. http://labtestsonline.org/understanding/analytes/hpv/tab/test accessed 2-26-12.

(6)Steben M, Duarte-Franco E. National Center for Biotechnology Information. “Human papillomavirus infection: epidemiology and pathophysiology.” 11-2007. http://www.ncbi.nlm.nih.gov/pubmed/17938014 accessed 2-24-12.

(7)The Rockefeller University. “Richard E. Shope.” 2004. http://www.rockefeller.edu/about/awards/lasker/rshope accessed 2-25-12.

(8)Nobelprize.org. "Harald zur Hausen - Autobiography". 2009. http://www.nobelprize.org/nobel_prizes/medicine/laureates/2008/hausen.html accessed 2-25-12.

(9)Kranjec*, Christian and  Banks, Lawrence. Journal of Virology. “A Systematic Analysis of Human Papillomavirus (HPV) E6 PDZ Substrates Identifies MAGI-1 as a Major Target of HPV Type 16 (HPV-16) and HPV-18 Whose Loss Accompanies Disruption of Tight Junctions.” 12-1-10. http://jvi.asm.org/content/85/4/1757.full accessed 12-24-12.

(10)National Institute of Allergy and Infectious Diseases. “Human Papillomavirus (HPV) and Genital Warts.” 10-20-10. http://www.niaid.nih.gov/topics/genitalWarts/understanding/Pages/treatment.aspx accessed 2-24-12.

(11)U.S. Food and Drug Administration. “HPV (human papillomavirus).” 1-24-11. http://www.fda.gov/ForConsumers/ByAudience/ForWomen/FreePublications/ucm118530.htm accessed 2-25-12.

(12)Centers for Disease Control and Prevention. “Genital HPV Infection - Fact Sheet.” 2-15-12. http://www.cdc.gov/std/HPV/STDFact-HPV.htm accessed 2-24-12.

(13)World Health Organization. “Human Papillomavirus and Related Cancers.” 11-15-10. http://apps.who.int/hpvcentre/statistics/dynamic/ico/country_pdf/XWX.pdf?CFID=5783749&CFTOKEN=44104296 accessed 2-26-12.