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UseTheCommandLine/sandbox/Genital wart

Genital warts (or condylomata acuminata, venereal warts, anal warts and anogenital warts) are symptoms of a highly contagious sexually transmitted disease caused by some types of human papillomavirus (HPV). It is spread through direct skin-to-skin contact, usually during oral, genital, or anal sex with an infected partner. Warts are the most easily recognized symptom of genital HPV infection. Although some types of HPV are known to cause cervical cancer and anal cancers, these are not the same types of HPV that cause genital warts.[1] Although 90% of those who contract HPV will not develop genital warts, those infected can still transmit the virus. Although estimates of incidence vary between studies, HPV is so common that nearly all sexually active people will get it at some point in their lives.[2]


HPV types 6 and 11 are most frequently the cause of genital warts. The Gardasil vaccine includes coverage for these types. While types 6 and 11 are considered low risk for progression to cancers, it is also possible to be infected with different varieties of HPV, such as a low-risk HPV that causes warts and a high-risk HPV, either at the same or different times.[3][2]

Signs and symptoms

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File:SOA-Condylomata-acuminata-female.jpg
severe case of genital warts in a female
File:SOA-Condylomata-acuminata-man.jpg
severe case of genital warts in a male

Genital warts may occur singly but are more often found in clusters. They may be found anywhere in the anal or genital area, and are frequently found on external surfaces of the body, including the penile shaft, scrotum, labia majora of the vagina, or around the anus. They can also occur on internal surfaces like the opening to the urethra, inside the vagina, on the cervix, or in the anus. In males they are frequently found on or around the head of the penis.

They can be as small as 1-5mm in diameter, but can also grow or spread into large masses in the genital or anal area. In some cases they look like small stalks. They may be hard ("keratinized") or soft. Their color can be variable, and sometimes they may bleed.

In most cases, there are no symptoms of HPV infection other than the warts themselves. Sometimes warts may cause itching, redness, or discomfort, especially when they occur around the anus. Although they are usually without other physical symptoms, an outbreak of genital warts may cause psychological distress, such as anxiety, in some people.[4]


Causes

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Transmission

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HPV is transmitted via breaks in the skin, such as the microscopic abrasions that occur during sexual activity. This allows viral particles to penetrate the skin and mucosal surfaces.

The types of HPV that cause warts are highly transmissible.

The immune system can eventually clear the virus through interleukins, which recruit interferons, which slow viral replication.[5]

Latency and Recurrence

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Although 90% of HPV infections are cleared by the body within two years of infection, it is possible for infected cells to undergo a latency (quiet) period, with the first occurrence or a recurrence of symptoms happening months or years later.[3] Latent HPV, even with no outward symptoms, is still transmissible to a sexual partner. If an individual has unprotected sex with an infected partner, there is a 70% chance that he or she will also become infected.

In individuals with a history of previous HPV infection, the appearance of new warts may be either from a new exposure to HPV, or from a recurrence of the previous infection. As many as one-third of people with warts will experience a recurrence.[6]

Chidren

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Anal or genital warts may be transmitted during birth. The presence of wart-like lesions on the genitals of young children has been suggested as an indicator of sexual abuse. However, genital warts can sometimes result from autoinoculated by warts elsewhere on the body, such as from the hands.[7] It has also been reported from sharing of swimsuits, underwear, or bath towels, and from non-sexual touching during routine care such as diapering. Genital warts in children are less likely to be caused by HPV subtypes 6 and 11 than adults, and more likely to be caused by HPV types that cause warts elsewhere on the body ("cutaneous types"). Surveys of pediatricians who are child abuse specialists suggest that in children younger than 4 years old, there is no consensus on whether the appearance of new anal or genital warts, by itself, can be considered an indicator of sexual abuse.[8]


Pathophysiology

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Further information: Human Papilloma Virus

Approximately 90% of genital warts cases are caused by HPV subtypes 6 and 11. Because these subtypes do not affect the DNA of infected cells, they are considered low risk. They are not associated by themselves with cancers.[9]

Individuals who are immunosupressed, such as by HIV may have more or larger warts, and their warts may also be more resistant to treatment. Immunosuppression may also be associated with higher rates of coinfection by multiple HPV types, including high-risk subtypes.[9]

Diagnosis

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Micrograph of a genital wart with the characteristic changes (parakeratosis, koilocytes, papillomatosis). H&E stain.

The diagnosis of genital warts is most often made visually, but may require confirmation by biopsy in some cases.[10] It may be confused with molluscum contagiosum. Genital warts, histopathologically, characteristically rise above the skin surface due to enlargement of the dermal papillae, have parakeratosis and the characteristic nuclear changes typical of HPV infections (nuclear enlargement with perinuclear clearing). Although DNA tests are available for diagnosis of high-risk HPV infections, genital warts are most often caused by low-risk HPV types, so DNA tests are not useful for diagnosis of genital warts or other low-risk HPV infections.[3]


Prevention

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See also: HPV vaccine

Gardasil (sold by Merck & Co.) is a vaccine that protects against human papillomavirus types 16, 18, 6, and 11. Types 6 and 11 cause genital warts, while 16 and 18 cause cervical cancer. The vaccine is preventive, not therapeutic, and must be given before exposure to the virus type to be effective, ideally before the beginning of sexual activity. The vaccine is approved by the US Food and Drug Administration for use in both males and females as early as 9 years of age.[11]

In the UK, Gardasil replaced Cervarix in September 2012[12] for reasons unrelated to safety.[13] Cervarix had been used routinely in young females from its introduction in 2008, but was only effective against HPV types 16 and 18, neither of which typically causes warts.


Management

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There is no cure for HPV, but there are methods to treat visible warts, which could reduce infectivity, although there are no trials studying the effectiveness of removing visible warts in reducing transmission.[14] Every year, Americans spend $200 million on the treatment of genital warts.[15] Genital warts may disappear without treatment, but sometimes eventually develop a fleshy, small raised growth. There is no way to predict whether they will grow or disappear. Warts can sometimes be identified because they show up as white when acetic acid is applied, but this method is not recommended on the vulva because microtrauma and inflammation can also show up as acetowhite.[5] Magnifying glasses or colposcope may also be used to aid in identifying small warts.[5]

Depending on the sizes and locations of warts (as well as other factors), a doctor will offer one of several ways to treat them. Podofilox is the first-line treatment due to its low cost.[16] Almost all treatments can potentially cause depigmentation or scarring.[14]

  • A 0.15% – 0.5% podophyllotoxin (also called podofilox) solution in a gel or cream. Marketed as Condylox (0.5%), Wartec (0.15%) and Warticon (0.15%),[17] it can be applied by the patient to the affected area and is not washed off. It is the purified and standardized active ingredient of the podophyllin (see below). Podofilox is safer and more effective than podophyllin.[17] Skin erosion and pain are more commonly reported than with imiquimod and sinecatechins.[18] Its use is cycled (2 times per day for 3 days then 4–7 days off); one review states that it should only be used for four cycles.[19]
  • Imiquimod (Aldara) is a topical immune response cream, applied to the affected area. It causes less local irritation than podofilox but may cause fungal infections (11% in package insert) and flu-like symptoms (less than 5% disclosed in package insert).[18]
  • Sinecatechins (marketed as Veregen and Polyphenon E) is an ointment of catechins (55% epigallocatechin gallate[5]) extracted from green tea and other components. Mode of action is undetermined.[20] It appears to have higher clearance rates than podophyllotoxin and imiquimod and causes less local irritation, but clearance takes longer than with imiquimod.[18]
  • Liquid nitrogen cryosurgery is safe for pregnancy. It kills warts 71–79% of the time, but recurrence is 38% to 73% 6 months after treatment.[5] Local infections have been reported.[5]
  • Trichloroacetic acid (TCA) is less effective than cryosurgery,[19] and is not recommended for use in the vagina, cervix, or urinary meatus.[5]
  • Surgical excision is best for large warts, and has a greater risk of scarring.[14]
  • Laser ablation does not seem to be any more effective than other physician-applied methods,[21] but is often used as a last resort and is extremely expensive.[5]
  • A 20% podophyllin anti-mitotic solution, applied to the affected area and later washed off. However, this crude herbal extract is not recommended for use on vagina, urethra, perianal area, or cervix,[5] and must be applied by a physician.[17] Reported reactions include nausea, vomiting, fever, confusion, coma, renal failure, ileus, and leukopenia; death has been reported with extensive topical application, or application on mucous membranes.[5]
  • Interferon can be used; it is effective, but it is also expensive and its effect is inconsistent.[19]
  • Electrocauterization can be used; it is an older procedure but recovery time is generally longer. In severe cases of genital warts, treatment may require general or spinal anesthesia. This is a surgical procedure. More effective than cryosurgery and recurrence is at a much lower rate.
  • Oral Isotretinoin is a therapy that has proven effective in experimental use, but is rarely used due to potentially severe side effects. In a small-scale study, low dose oral isotretinoin showed considerable efficacy and may represent an alternative systemic form of therapy for Genital Warts. Yet, albeit this indicative evidence not many studies have been conducted to further confirm the findings. In most countries this therapy is currently unapproved and only used as an alternative therapy if other therapies failed.[22]
Discontinued
  • A 5% 5-fluorouracil (5-FU) cream was used, but it is no longer considered an acceptable treatment due to the side-effects.[5]

Podophyllin, podofilox and Isotretinoin should not be used during pregnancy, as they could cause birth defects in the fetus.

Prognosis

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Although warts may cause substantial psychological distress in infected people, they generally do not pose any significant health threat.

Epidemiology

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Genital HPV infections have an estimated prevalence in the US of 10–20% and clinical manifestations in 1% of the sexually active adult population.[19] US incidence of HPV infection has increased between 1975 and 2006.[19] About 80% of those infected are between the ages of 17–33.[19] Although treatments can remove the warts, they do not remove the HPV, so warts can recur after treatment (about 50–73% of the time[23]). Warts can also spontaneously regress (with or without treatment).[19]

Traditional theories postulated that the virus remained in the body for a lifetime. However, studies using sensitive DNA techniques have shown that through immunological response the virus can either be cleared or suppressed to levels below what polymerase chain reaction (PCR) tests can measure. One study testing genital skin for subclinical HPV using PCR found a prevalence of 10%.[19]

References

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  1. ^ US National Cancer Institute. "HPV and Cancer". Retrieved 2 January 2013.
  2. ^ a b US Centers for Disease Control. "Genital HPV Infection - Fact Sheet". Retrieved 2 January 2013.
  3. ^ a b c Juckett, G.; Hartman-Adams, H. (2010 Nov 15). "Human papillomavirus: clinical manifestations and prevention". American Family Physician. 82 (10): 1209–13. PMID 21121531. {{cite journal}}: Check date values in: |date= (help)
  4. ^ Cite error: The named reference JEADV-2012 was invoked but never defined (see the help page).
  5. ^ a b c d e f g h i j k Mayeaux EJ, Dunton C (July 2008). "Modern management of external genital warts". J Low Genit Tract Dis. 12 (3): 185–192. doi:10.1097/LGT.0b013e31815dd4b4. PMID 18596459.{{cite journal}}: CS1 maint: date and year (link)
  6. ^ {{ PMID 22131115}}
  7. ^ Cite error: The named reference UK-guideline-2007 was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference Peds-Rev-2011 was invoked but never defined (see the help page).
  9. ^ a b Cite error: The named reference JAAD-I-2012 was invoked but never defined (see the help page).
  10. ^ [1]
  11. ^ United States Food and Drug Administration. "Gardasil". Approved Products. Retrieved 1 January 2013.
  12. ^ UK Department of Health. "Your guide to the HPV vaccination from September 2012". Retrieved 1 January 2013.
  13. ^ UK Medicines and Healthcare products Regulatory Agency. "Human papillomavirus vaccine Cervarix: safety review shows balance of risks and benefits remains clearly positive". Retrieved 1 January 2013.
  14. ^ a b c Kodner CM, Nasraty S (December 2004). "Management of genital warts". Am Fam Physician. 70 (12): 2335–2342. PMID 15617297.{{cite journal}}: CS1 maint: date and year (link)
  15. ^ "STI Awareness: Genital Warts". Planned Parenthood Advocates of Arizona. 2012-04-18. Retrieved 2012-04-20.
  16. ^ Fox PA, Tung MY (2005). "Human papillomavirus: burden of illness and treatment cost considerations". Am J Clin Dermatol. 6 (6): 365–381. doi:10.2165/00128071-200506060-00004. PMID 16343025.
  17. ^ a b c von Krogh G, Longstaff E (December 2001). "Podophyllin office therapy against condyloma should be abandoned". Sex Transm Infect. 77 (6): 409–412. doi:10.1136/sti.77.6.409. PMC 1744412. PMID 11714936.{{cite journal}}: CS1 maint: date and year (link)
  18. ^ a b c Meltzer SM, Monk BJ, Tewari KS (March 2009). "Green tea catechins for treatment of external genital warts". Am. J. Obstet. Gynecol. 200 (3): 233.e1–7. doi:10.1016/j.ajog.2008.07.064. PMID 19019336.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  19. ^ a b c d e f g h Scheinfeld N, Lehman DS (2006). "An evidence-based review of medical and surgical treatments of genital warts". Dermatol. Online J. 12 (3): 5. PMID 16638419.
  20. ^ "Veregen label information" (PDF). Retrieved 2013-01-01.
  21. ^ O'Mahony C (2005). "Genital warts: current and future management options". Am J Clin Dermatol. 6 (4): 239–243. doi:10.2165/00128071-200506040-00004. PMID 16060711.
  22. ^ Virendra N. Sehgal MD, Govind Srivastava MD, Kabir Sardana MD (May 2006). "Isotretinoin – unapproved indications/uses and dosage: a physician's reference". International Journal of Dermatology. 45 (6): 772–777. doi:10.1111/j.1365-4632.2006.02830.x. PMID 16796650.{{cite journal}}: CS1 maint: date and year (link) CS1 maint: multiple names: authors list (link)
  23. ^ CDC. (2004). REPORT TO CONGRESS: Prevention of Genital Human Papillomavirus Infection.
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Category:Infections with a predominantly sexual mode of transmission Category:Papillomavirus associated diseases Category:Virus-related cutaneous conditions


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