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Human papillomavirus infection

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Human papillomavirus infection
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"HPV" redirects here. For other uses, see HPV (disambiguation).
The Papillomavirus article covers the general biological features of human and animal papillomaviruses.

Papillomaviruses are a diverse group of DNA-based viruses that infect the skin and mucous membranes of humans and a variety of animals. More than 100 different human papillomavirus (HPV) types have been characterized. Some HPV types cause benign skin warts, or papillomas, for which the virus family is named. HPVs associated with the development of such "common warts" are transmitted environmentally or by casual skin-to-skin contact.

A separate group of about 30 HPVs are typically transmitted through sexual contact. Genital HPV infection is very common, with estimates suggesting that up to 75% of women will become infected with one or more of the sexually transmitted HPV types at some point during adulthood (Baseman and Koutsky, 2005). Some sexually transmitted HPVs, such as types 6 and 11, can cause genital warts. However, most HPV types that infect the genitals tend not to cause noticeable symptoms. Persistent infection with a subset of about a dozen so-called "high-risk" sexually transmitted HPVs, including types 16, 18, 31, 33, 35, 39, 45 and 51 can lead to the development of cervical dyskaryosis, which may in turn lead to cancer of the cervix. HPV infection is a necessary factor in the development of nearly all cases of cervical cancer (Walboomers 1999).

Cervical Pap smear testing is used to detect HPV-induced cellular abnormalities. This allows targeted surgical removal of pre-cancerous lesions prior to the development of invasive cervical cancer. In the absence of Pap testing or treatment, about 1% of women with genital HPV infections will eventually go on to develop cervical cancer. Although the widespread use of Pap testing has reduced the incidence and lethality of cervical cancer in developed countries, the disease still kills several hundred thousand women per year worldwide. A recently approved HPV vaccine that blocks initial infection with several of the most common sexually transmitted HPV types may lead to further decreases in the incidence of HPV-induced cancer (Lowy and Schiller 2006).

Notable HPV types and associated diseases

HPV-induced diseases

Disease HPV strain
Common warts 2, 7
Plantar warts 1, 2, 4
Flat cutaneous warts 3, 10
Anogenital warts 6, 11, 42, 43, 44, 55 and others
Genital malignancies 16, 18, 31, 33, 35, 39, 45, 51
Epidermodysplasia verruciformis more than 15 strains
Focal epithelial hyperplasia (oral) 13, 32
Oral papillomas 6, 7, 11, 16, 32

Skin warts

  • Common warts: Some "cutaneous" HPV types, such as HPV-1 and HPV-2, cause common skin warts. Common warts are often found on the hands and feet, but can also occur in other areas, such as the elbows or knees. Common warts have a characteristic cauliflower-like surface and are typically slightly raised above the surrounding skin. Cutaneous HPV types do not usually cause genital warts and are not associated with the development of cancer.
  • Plantar warts are found on the soles of the feet. Plantar warts closely resemble common warts.
  • Subungual or periungual warts form under the fingernail (subungual), around the fingernail or on the cuticle (periungual). They may be more difficult to treat than warts in other locations.
  • Flat warts: Flat warts are most commonly found on the arms, face or forehead. Like common warts, flat warts occur most frequently in children and teens. In people with normal immune function, flat warts are not associated with the development of cancer.

Genital warts

Genital or anal warts (condylomata acuminata or venereal warts) are the most easily recognized sign of genital HPV infection. Although a wide variety of HPV types can cause genital warts, types 6 and 11 account for about 90% of all cases (Greer 1995)(Gearheart et al, 2004). Most people who acquire genital wart-associated HPV types clear the infection rapidly without ever developing warts or any other symptoms. People may transmit the virus to others even if they don't display overt symptoms of infection.

HPV types that tend to cause genital warts are not the same ones that cause cervical cancer. However, since an individual can be infected with multiple types of HPV, the presence of warts does not rule out the possiblity of high risk strains of the virus also being present.

Cancer

HPV-induced cancers

About a dozen HPV types (including types 16, 18, 31 and 45) are called "high-risk" types because they can cause cervical cancer, as well as anal cancer, vulvar cancer, head and neck cancers, and penile cancer (Parkin 2006). HPV-induced cancers often have viral sequences integrated into the cellular DNA. Some of the HPV "early" genes, such as E6 and E7, are known to act as oncogenes that promote tumor growth and malignant transformation.

The p53 protein prevents cell growth in the presence of DNA damage primarily through the BAX domain, which blocks the anti-apoptotic effects of the mitochondrial BCL-2 receptor. In addition, p53 also upregulates the p21 protein, which blocks the formation of the Cyclin D/Cdk4 complex, thereby preventing the phosphorylation of RB and, in turn, halting cell cycle progression by preventing the activation of E2F. In short, p53 is a tumor suppressor gene that arrests the cell cycle when there is DNA damage. The E6 and E7 proteins work by inhibiting tumor suppression genes involved in that pathway: E6 inhibits p53, while E7 inhibits p53, p21, and RB.

Genome organization of human papillomavirus type 16, one of the subtypes known to cause cervical cancer. (E1-E7 early genes, L1-L2 late genes: capsid)

A history of infection with one or more high-risk HPV types is believed to be a prerequisite for the development of cervical cancer; according to the American Cancer Society, women with no history of the virus do not develop this type of cancer. However, most HPV infections are cleared rapidly by the immune system and do not progress to cervical cancer. Because the process of transforming normal cervical cells into cancerous ones is slow, cancer occurs in people who have been infected with HPV for a long time, usually over a decade or more (Greenblatt, 2005; Sinal and Woods, 2005).

Sexually transmitted HPVs also cause a major fraction of anal cancers and approximately 25% of cancers of the mouth and upper throat (known as the oropharynx) (see figure). The latter commonly present in the tonsil area and HPV is linked to the increase in oral cancers in non-smokers (Gillison 2000, 2006). Engaging in anal sex or oral sex may increase the risk of developing these types of cancers.

Although it has been proposed that HPVs may induce other forms of cancer, including breast cancer, colorectal cancer and non-melanoma skin cancer, a causal relationship between HPV infection and these cancer types has not yet been firmly established.[citation needed]

Respiratory papillomatosis

HPV types 6 and 11 can cause a rare condition known as recurrent respiratory papillomatosis, in which warts form on the larynx or other areas of the respiratory tract (Wu et al., 2003; Sinal and Woods, 2005). These warts can recur frequently, may require repetitive surgery, may interfere with breathing, and in extremely rare cases can progress to cancer (Moore et al., 1999; Sinal and Woods, 2005).

Epidemiology

Cutaneous HPVs

Infection with cutaneous HPVs is ubiquitous (Antonsson 2000). Some HPV types, such as HPV-5, may establish infections that persist for the lifetime of the individual without ever manifesting any clinical symptoms. Like remora suckerfish that hitchhike harmlessly on sharks, these HPV types can be thought of as human commensals. Other cutaneous HPVs, such as HPV types 1 or 2, may cause common warts in some infected individuals. Skin warts are most common in childhood and typically appear and regress spontaneously over the course of weeks to months. About 10% of adults also suffer from recurring skin warts. All HPVs are believed to be capable of establishing long-term "latent" infections in small numbers of stem cells present in the skin. Although these latent infections may never be fully eradicated, immunological control is thought to block the appearance of symptoms such as warts. Immunological control is likely HPV type-specific, meaning that an individual may become immunologically resistant to one HPV type while remaining susceptible to other types.

Genital HPVs

A large increase in the incidence of genital HPV infection occurs at the age when individuals begin to engage in sexual activity (see figure). The great majority of genital HPV infections never cause any overt symptoms and are cleared by the immune system in a matter of months. As with cutaneous HPVs, immunity is believed to be HPV type-specific. A subset of infected individuals may fail to bring genital HPV infection under immunological control. Lingering infection with high-risk HPV types, such as HPVs 16, 18, 31 and 45, can lead to the development of cervical cancer or other types of cancer (Schiffman and Castle 2005). High-risk HPV types 16 and 18 are together responsible for over 70% of cervical cancer cases (Baseman and Koutsky, 2005; Cohen, 2005). Type 16 causes 41 to 54% of cervical cancers (Noel et al., 2001; Baseman and Koutsky, 2005) and accounts for an even greater majority of HPV-induced vaginal/vulvar cancers (Edwards et al., 2005), penile cancers, anal cancers and head and neck cancers (Bolt et al., 2005).

Perinatal transmission

Although genital HPV types are sometimes transmitted from mother to child during birth, the appearance of genital HPV-related diseases in newborns is rare. Perinatal transmission of HPV types 6 and 11 can result in the development of juvenile-onset recurrent respiratory papillomatosis (JORRP). JORRP is very rare, with rates of about 2 cases per 100,000 children in the United States (Sinal and Woods 2005). Although JORRP rates are substantially higher if a woman presents with genital warts at the time of giving birth, the risk of JORRP in such cases is still less than 1%.

Prevention

Most people become infected with various cutaneous HPV types during childhood. Papillomaviruses have a sturdy outer protein shell or "capsid" that renders them capable of lingering in the environment for long periods of time. Avoiding contact with contaminated surfaces, such as the floors of communal showers or airport security lines, might reduce the risk of cutaneous HPV infection. Treating common warts soon after they first appear may also reduce the spread of the infection to additional sites.

Genital HPV infections may be distributed widely over genital skin and mucosal surfaces, and transmission can occur even when there are no overt symptoms. Several strategies should be employed to minimize the risk of developing diseases caused by genital HPVs:

Pap smear

Main article: Pap smear
ThinPrep Pap smear with group of normal cervical cells on left and HPV-infected cells on right

Papanicolaou screening, colloquially known as "Pap" smear testing, is an effective strategy for reducing the risk of invasive cervical cancer. In March 2003, the US FDA approved HPV DNA testing as a primary screening tool for detecting high-risk HPV infections that may lead to cervical cancer. Pap smear testing has proven to be one of the most successful screening tests in the history of medicine, but ACOG states the even the newer liquid based cytology methods (Thinprep and Surepath) may miss 15-35% of CIN3's and cancer. By adding the HPV test to all women over the age of thirty, it improves the sensitivity of the cytology test to nearly 100%. The HPV DNA test, which is marketed by Digene, can also serve as an adjunct to Pap smear testing, and may be ordered in response to abnormal Pap smear results. It is the gold standard for the resolution of ASCUS pap results, as detailed in the ALTS trial. Detailed inspection of the cervix by colposcopy may be indicated if abnormal cells are detected by routine Pap smear.

It has been suggested that Pap smear screening for anal cancer might be of benefit for relatively promiscuous individuals, for example some sub-populations of gay men (Chin-Hong 2005).

HPV testing

An HPV test detects certain human papillomaviruses (HPVs), depending on the test. Certain types of sexually transmitted HPVs can cause cervical cancer. Persistent infection with one or more of about a dozen of these "high-risk" HPV types is an important factor in nearly all cases of cervical cancer. The development of HPV-induced cervical cancer is a slow process that generally takes many years. During this development phase, pre-cancerous cells can be detected by annual or semi-annual cervical cytology screening or "Pap test." More recently a method for detecting the DNA of high-risk HPVs has been added to the range of clinical options for cervical cancer screening. The US FDA has approved this "hybrid-capture" test, marketed by Digene, for use as an alternative or adjunct to Pap testing.

The Pap test involves taking cells from the cervix and putting them on a small glass slide and examining them under a microscope to look for abnormal cells. This method is 70% to 80% effective in detecting HPV. A more sensitive method is a “Thin Prep,” in which the cells from the cervix are placed in a liquid solution. This test is 85% to 95% effective in detecting HPV. The last Pap test method is mainly used on women over 30. It is a combination Pap-HPV DNA test. If this test comes back negative women can usually wait 3 years before having the test done again (Richman, 2005, p. 168).

The Center for Disease Control (CDC) recommends that women get a Pap test no later than 3 years after their first sexual encounter and no later than 21 years of age. Women should have a Pap test every year until age 30. After age 30, women should discuss risk factors with their health care provider to determine whether a Pap test should be done yearly. If risk factors are low and previous Pap tests have been negative, most women only need to have tests every 2-3 years until 65 years of age (Centers for Disease Control 2005). Since these screening tools have been developed there has been a 70% decrease in cervical cancer deaths over the last 50 years (Richman, 2005).

According to the CDC there is currently no test commercially available to determine infection in men. Genital warts are the only visible sign of HPV in men and can be identified with a visual check of the genital area. Vinegar solutions have been used to identify flat warts by making them more distinct, but most providers have found this technique helpful only in moist areas, such as the female genital tract.(http://www.cdc.gov/STD/HPV/STDFact-HPV-and-men.htm#test [January 2007]).

Vaccine

Main article: HPV vaccine

On June 8, 2006, the FDA approved Gardasil, a prophylactic HPV vaccine which is marketed by Merck. The vaccine trial,[1] conducted in adult women with a mean age of 23, showed protection against initial infection with HPV types 16 and 18, which together cause 70 percent of cervical cancers. HPV types 16 and 18 also cause anal cancer in men and women. The trial also showed 100% efficacy against persistent infections, not just incident infections. The vaccine also protects against HPV types 6 and 11, which cause 90 percent of genital warts. Women aged nine through twenty-six can be vaccinated, though the trial did not test minors. GlaxoSmithKline is expected to seek approval for a prophylactic vaccine targeting HPV types 16 and 18 early in 2007, known as Cervarix. Since the current vaccine will not protect women against all the HPV types that cause cervical cancer, it will be important for women to continue to seek Pap smear testing, even after receiving the vaccine. The Centers for Disease Control and Prevention (CDC) recommend vaccinating a woman who has already been diagnosed with HPV (October 2006)[1].

Avoiding risky sexual behavior

The fact that prostitutes have much higher rates of cervical cancer than nuns was a key early observation leading researchers to speculate about a causal link between sexually transmitted HPVs and cervical cancer (zur Hausen 1994). It remains clear that people with greater numbers of sexual partners are at increased risk of developing genital HPV-related diseases. Co-infection with other sexually transmitted pathogens, such as HIV, may also increase the risk of developing HPV-related diseases.

Condoms

Although condoms are highly effective for preventing the transmission of other sexually transmitted diseases (STDs), recent studies have concluded that condoms only offer partial protection, at best, against the transmission of genital HPVs (Holmes 2004; Winer 2006). This may be due to the fact that HPVs can infect genital skin areas that are not covered by condoms. On the other hand, some studies have suggested that regular condom use can effectively limit the ongoing persistence and spread of HPV to additional genital sites in individuals who are already infected (Moscicki 2005; Bleecker 2005). Thus, condom use may reduce the risk that infected individuals will progress to cervical cancer or develop additional genital warts. A 2006 study of 82 college students suggests that condoms can be up to 70% effective for preventing genital HPV infection if used for every sexual encounter (Winer 2006). Both Planned Parenthood and the Centers for Disease Control recommend condom use to reduce the risk of HPV-related diseases.[citation needed]

Microbicides

Ongoing research has suggested that several inexpensive chemicals might serve to block HPV transmission if applied to the genitals prior to sexual contact (Howett 2005). These candidate agents, which are known as topical microbicides, are currently undergoing clinical efficacy testing. A recent study indicates that some sexual lubricant brands that use a gelling agent called carrageenan can inhibit papillomavirus infection in vitro (Buck 2006). Clinical trials are needed to determine whether carrageenan-based sexual lubricant gels are effective for blocking the sexual transmission of HPVs in vivo.

Avoiding smoking

Tobacco smoking increases the risk of developing invasive cervical cancer, as well as other HPV-induced cancers. Smoking decreases the ability to absorb folic acid, and taking folic acid is a respected way of treating cervical dysplasia, an extremely common symptom of HPV.

Treatment

Therapies are addressed in main articles covering the various HPV-related diseases.

Notes

  1. ^ Lancet. 2006 Apr 15;367(9518):1247-55

References

  1. Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG. 2000. The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses. Journal of Virology 74(24):11636. PMID 11090162
  2. Baseman J.G. and Koutsky L.A. 2005. The epidemiology of human papillomavirus infections. Journal of Clinical Virology, 32(1): S16-24. PMID 15753008. *Note: the abstract of this paper states that 60% of initially HPV-negative women became infected over the course of five years of follow-up. 20% of the women in the study population were already infected at the onset of the study. This supports the conservative 75% figure given in the introduction section.
  3. Bleeker MC, Berkhof J, Hogewoning CJ, Voorhorst FJ, van den Brule AJ, Starink TM, Snijders PJ, Meijer CJ. 2005. "HPV type concordance in sexual couples determines the effect of condoms on regression of flat penile lesions." British Journal of Cancer. 92(8):1388-92. PMID 15812547
  4. Bolt J., Vo Q.N., Kim W.J., McWhorter A.J., Thomson J., Hagensee M.E., Friedlander P., Brown K.D., and Gilbert J. 2005. The ATM/p53 pathway is commonly targeted for inactivation in squamous cell carcinoma of the head and neck (SCCHN) by multiple molecular mechanisms. Oral Oncology, 41(10): 1013-1020. Abstract available.
  5. Buck CB, Thompson CD, Roberts JN, Muller M, Lowy DR, Schiller JT. 2006. Carrageenan is a potent inhibitor of papillomavirus infection. Public Library of Science - Pathogens 2(7):e69. PMID 16839203
  6. Chin-Hong PV, Vittinghoff E, Cranston RD, Browne L, Buchbinder S, Colfax G, Da Costa M, Darragh T, Benet DJ, Judson F, Koblin B, Mayer KH, Palefsky JM. 2005. Age-related prevalence of anal cancer precursors in homosexual men: the EXPLORE study. J Natl Cancer Inst. 97(12):896-905. PMID 15956651
  7. Cohen J. 2005. High Hopes and Dilemmas for a Cervical Cancer Vaccine. Science, 308(5722):618-621.
  8. de Villiers E.M., Fauquet C, Broker TR, Bernard HU., and zur Hausen H. 2004. Classification of papillomaviruses. Virology, 324(1): 17-27. Abstract available.
  9. Edwards Q.T., Saunders-Goldson S., Morgan P.D., Maradiegue A., and Macri C. 2005. Vulvar Intraepithelial Neoplasia. Advance for Nurse Practitioners. March, 2005 issue. pp. 49-52.
  10. Gardiner Harris, U.S. Approves Cervical Cancer Vaccine, N.Y. Times (Jun. 6, 2006).
  11. Gearheart P.A., Randall T.C., Buckley R.M.Jr. 2004. Human Papillomavirus. eMedicine, December 2004.
  12. Gillison, M., Wayne M. Koch, Randolph B. Capone, Michael Spafford, William H. Westra, Li Wu, Marianna L. Zahurak, Richard W. Daniel, Michael Viglione, David E. Symer, Keerti V. Shah, David Sidransky. 2000 Evidence for a Causal Association Between Human Papillomavirus and a Subset of Head and Neck Cancers. Journal of the National Cancer Institute, Vol. 92, No. 9, 709-720, May 3, 2000 © 2000 Oxford University Press
  13. Gillison, M. 2006. Human Papillomavirus and Prognosis of Oropharyngeal Squamous Cell Carcinoma; Implications for Clinical Research in Head and Neck Cancer. Journal of Clinical Oncology, Vol 24, No 36 (December 20), 2006: pp. 5623-5625
  14. Greenblatt R.J. 2005. Human papillomaviruses: Diseases, diagnosis, and a possible vaccine. Clinical Microbiology Newsletter, 27(18), 139-145. Abstract available.
  15. Greer CE, Wheeler CM, Ladner MB, Beutner K, Coyne MY, Liang H, Langenberg A, Yen TS, Ralston R. 1995. Human papillomavirus (HPV) type distribution and serological response to HPV 6 virus-like particle in patients with genital warts. Journal of Clinical Microbiology 33(8):2058–2063. PMID 7559948
  16. Holmes, K. K., R. Levine and M. Weaver (2004). "Effectiveness of condoms in preventing sexually transmitted infections." Bull World Health Organ 82(6): 454-61 PMID 15356939.
  17. Howett MK, Kuhl JP. 2005. "Microbicides for prevention of transmission of sexually transmitted diseases." Current Pharmaceutical Design. 11(29):3731-46. PMID 16305508
  18. Lowy, D. R. and J. T. Schiller (2006). "Prophylactic human papillomavirus vaccines." J Clin Invest 116(5): 1167-73 PMID 16670757.
  19. Moore C.E., Wiatrak B.J., McClatchey K.D., Koopmann C.F., Thomas G.R., Bradford C.R. and Carey T.E. 1999. High-risk human papillomavirus types and squamous cell carcinoma in patients with respiratory papillomas. Otolaryngology, 120(5): 698-705.
  20. Moscicki AB. 2005.. "Impact of HPV infection in adolescent populations." Journal of Adolescent Health. 37(6 Suppl):S3-9. PMID 16310138
  21. Noel J.C., Lespagnard L., Fayt I., Verhest A., and Dargent J.L. 2001. Evidence of human papilloma virus infection but lack of Epstein-Barr virus in lymphoepithelioma-like carcinoma of uterine cervix: Report of two cases and review of the literature. Human Pathology, 32(1): 135-138.
  22. Parkin, D. M. (2006). "The global health burden of infection-associated cancers in the year 2002." Int J Cancer 118(12): 3030-44 PMID 16404738.
  23. Schiffman M, Castle PE. 2005. The promise of global cervical-cancer prevention. New England Journal of Medicine. 353(20):2101-4 PMID 16291978
  24. Sinal S.H. and Woods C.R. 2005. Human papillomavirus infections of the genital and respiratory tracts in young children. Seminars in Pediatric Infectious Diseases, 16(4): 306-316.
  25. Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Munoz N. 1999. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. "The Journal of Pathology." 189(1):12-9. PMID 10451482.
  26. Winer RL, Hughes JP, Feng Q, O'Reilly S, Kiviat NB, Holmes KK, Koutsky LA. 2006. Condom use and the risk of genital human papillomavirus infection in young women. New England Journal of Medicine. 354(25):2645 PMID: 16790697
  27. Wu R. Sun S., Steinberg B.M. 2003. Requirement of STAT3 activation for differentiation of mucosal stratified squamous epithelium. Molecular Medicine, 9(3/4), 77-84. Available.
  28. zur Hausen, H., de Villiers, E. M. 1994. Human papillomaviruses. Annual Review of Microbiology, 48:427 PMID 7826013.

See also

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