AUTHOR AND EDITOR INFORMATION

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• Miscellaneous
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INTRODUCTION

Section 2 of 11  

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• Follow-up
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Background

Until the 19th century, genital warts (GWs) were believed to be a form of syphilis or gonorrhea. The viral etiology of warts was established in 1907 by inoculation of wart filtrates into skin, inducing papillomas at the injection site. Today, condyloma acuminatum, or GWs, generally is recognized as benign proliferations of the anogenital skin and mucosa that result from infection with human papillomavirus (HPV). The HPV family has at least 83 well-documented genotypes. Some believe that the number of HPV types has already approached 130 or more. Despite the generally benign nature of the proliferations, certain types of HPV can place patients at a high risk for anogenital cancer.

Pathophysiology

GWs are a result of HPV infection, which is believed to be acquired by inoculation of the virus into the epidermis via defects in the epithelium (eg, maceration of the skin). Autoinoculation of virus into opposed lesions is common. Spread of HPV infection is usually through skin-associated virus and not from blood-borne infection. Probably, cell-mediated immunity (CMI) plays a significant role in wart regression; patients with CMI deficiency are particularly susceptible to HPV infection and are notoriously difficult to treat.

Frequency

United States

Epidemiological studies show GWs to be one of the most common sexually transmitted diseases (STDs). Annually, 500,000-1,000,000 new cases of GWs occur in the United States. Roughly, 10% of the general population or 24 million people have been infected by genital HPV at some time in their life. At least 2 studies have documented a 7- to 8-fold increase in the number of patients with GWs seen at physicians' offices from the 1950s to the mid 1980s; surpassing the number of office visits for genital herpes. Moreover, it must be emphasized that the prevalence of subclinical HPV infection is likely to be several times higher than the documented prevalence of GWs. Fortunately, according to 1996 figures, the magnitude of the increasing trend of HPV infection has slowed down.

International

GWs have affected as many as 30 million individuals worldwide.

Mortality/Morbidity

• Although anogenital warts generally are benign, their significance is drawn from the increased risk of malignancy secondary to HPV infection. Specifically, HPV types 16, 18, 31, 33, and 51 are associated with the greatest prevalence of anogenital malignancy.
• Infectivity of anogenital warts may be up to two thirds of sexual contacts.
• High concordance for the same HPV type has been found among sexual partners.

Race

In the United States, African Americans have a rate of HPV infection that is 1.5 times higher than their white counterparts.

Sex

In a well-defined population study, the female-to-male ratio has been reported to be 1.4:1. The Centers for Disease Control and Prevention (CDC) reports have demonstrated that this disease affects females more frequently than males.

Age

The highest incidence of GWs consistently is found in young adults aged 15-25 years. This observation tends to hold true even after adjustment for lifetime number of sexual partners, which itself is a significant risk factor for HPV infection. In a population study, 80% of the individuals who were affected were aged 17-33 years.

CLINICAL

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History

• Warts generally do not become clinically apparent until several months after inoculation with HPV.
• Lesions follow a slow and indolent course and may develop by inoculation from opposing surfaces.

Physical

• Anogenital warts consist of pink-to-brown papillomatous papules or nodules of the genitalia, perineum, crural folds, and anus.
• • Warts vary in size and can form large, exophytic, cauliflowerlike masses.
  • Discrete papules, 1-3 mm in size can present on the shaft of the penis.
  • The growth can extend into the vagina, urethra, cervix, perirectal epithelium, anus, and rectum.

Causes

The definitive cause of anogenital warts is HPV. See Human Papillomavirus.

• HPV is part of the papovavirus class, which includes SV 40, BK, and JC virus.
• The HPV capsid lacks an envelope, which makes it very stable and resistant to various treatments.
• No serologic typing of HPV is available because of the lack of consistent in vitro culture methods.
• • Typing of HPV is according to genotype, which usually is determined by molecular hybridization techniques using molecularly cloned HPV DNA of known type as the standard.
  • Two HPV are said to be of different types when their DNA hybridize (bind) less than 50% as efficiently to each other as to themselves.
• More than 30 types of HPV (of nearly 80 sequenced to date) have been found in genital warts. They are very host specific. These viruses do not infect laboratory animals and are not susceptible to acyclovir.
• As a rule, HPV types causing common warts of the skin do not infect moist epithelium and vice versa.
• Multiple clinical associations with unique genotypes of HPV have been documented. HPV types and their association with the clinical disease are as follows:
• • Plantar warts - 1, 2, 4, 60, and 63
  • Common warts - 1, 2, 4, 26, 27, 29, 57, 65, and 75-78
  • Meat/poultry/fish handlers - 1-4, 7, 10, and 28
  • Flat warts - 3, 10, 27, 28, 38, and 49
  • Epidermodysplasia verruciformis - 2, 3, 5, 8, 9, 10, 12, 14, 15, 17, 19, 20, 21-25, 28, 36-38, 40, 47, and 50
  • Squamous cell carcinoma or actinic keratosis - 14, 16, 18, 36, and 41
  • Squamous cell carcinoma, keratoacanthoma type - 7, 9, 16, 29, and 37
  • Squamous cell carcinoma, in immunocompromised - 48 and 60
  • Bowen disease (nongenital) - 2, 16, 26-29, 31, 33, 34, 54, 56, 58, 61, 62, and 73
  • Melanoma - 16, 18, 35, and 38
  • Oral focal epithelial hyperplasia - 13 and 32
  • Oral papilloma - 11, 7, 32, 57, 72, and 73
  • Laryngeal papilloma (recurrent respiratory papillomatosis) - 2, 6, 11, 16, 30, 40, and 57
  • Conjunctival papillomas and cancer - 6, 11, and 16
  • Epidermal cyst - 57, 60
  • Condyloma acuminatum -1-5, 6, 11, 10, 16, 18, 30, 31, 33, 35, 39-45, 51-59, 70, and 83
  • Giant condyloma of Buschke and Löwenstein and other verrucous carcinoma - 6, 11, 57, 72, and 73
  • Bowenoid papulosis - 16, 34, 39, 40, 42, and 45
  • Vulvar intraepithelial neoplasia - 56, 59-64, 67, and 71
  • Cervical squamous intraepithelial lesions (SIL)
  • • Low-grade squamous intraepithelial lesions (LGSIL) - 6, 11, 16, 18, 26, 27, 30, 31, 33-35, 40, 42-45, 51-58, 61, 62, 67-69, 71-74, and 82
    • High-grade squamous intraepithelial lesions (HGSIL) - 6, 11, 16, 18, 31, 33, 35, 39, 42, 44, 45, 51, 52, 56, 58, 59, 61, 64, 66, 68, and 82
  • Cervical cancer - 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66
  • High-risk HPV types
  • • Southeast Asia - 18
    • West Africa - 45
    • Central/South America - 39 and 59

DIFFERENTIALS

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Other Problems to be Considered

Anogenital malignancy
Anogenital warts in children
Fordyce spots
Laryngeal papillomatosis of neonates and infants
Syphilis (GWs sometimes can be confused with syphilitic lesions, condyloma lata)
Verrucous carcinoma of genitalia (giant condyloma of Buschke-Löwenstein)

WORKUP

Section 5 of 11  

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Lab Studies

• Diagnosis usually is made clinically; it may be helped by the application of acetic acid and biopsy.
• Identification of precise HPV genotypes is available only in research laboratories by using DNA hybridization techniques.¹
• • This technique includes Southern blot (highly sensitive and also most time consuming), dot blot, and in situ hybridization.
  • Others methods include enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG) antibody (Ab) against HPV 16 capsid.
• Certain screening tests are available with a relatively high sensitivity and specificity; they include the following:
• • ViraPap
  • ThinPrep Pap
  • Hybrid capture II

Other Tests

• Acetic acid test
• • Soaking acetic acid into suspicious lesions can enhance the degree of suspicion in lesions without classic features.
  • The method involves applying a 3-5% acetic acid–moistened gauze pad for 5-10 minutes on suspected lesions of the penis, cervix, labia, or perianal area.
  • Inconspicuous, flat, genital lesions that might be difficult to assess become visible. Dysplastic and neoplastic tissues turn white (acetowhite).
  • False-positive results are common and can result from anything that causes parakeratosis (eg, candidiasis, psoriasis, lichen planus, healing epithelium, sebaceous glands).
  • This technique can be combined with the use of colposcopy to examine cervical lesions.
  • The acetic acid test is reserved only for suspicious lesions and should not be used for routine screening.

Histologic Findings

Histopathology can elucidate diagnosis in most cases.

• Verrucae consist of acanthotic epidermis with papillomatosis, hyperkeratosis, and parakeratosis.
• Elongated rete ridges may point to the center of the wart and dermal capillary vessels may be thrombosed.
• Koilocytes are indicative of HPV infection. These are large keratinocytes with an eccentric, pyknotic nucleus surrounded by a perinuclear halo.
• Anogenital warts lack a granular layer and tend to be more papillomatous and vascular than common warts.
• An electron microscope may show viral particles in nuclei.
• Immunohistochemical staining with the peroxidase-antiperoxidase technique stains cells infected by viral particles.

TREATMENT

Section 6 of 11  

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Medical Care

Treatment is aimed at destruction of the warty growths rather than elimination of the virus.

• Subclinical infection probably is lifelong, and there is no cure.
• • Most partners are likely to be subclinically infected with HPV, even if they do not have exophytic lesions.
  • Use of condoms may reduce transmission of the virus to uninfected partners.
• Standard therapies for GWs can remove most warts; however, no ideal treatment is available for all warts and all patients.
• • Caustics/acids - 80-90% bichloracetic acid (BCA) or trichloroacetic acid (TCA)
  • Podophyllin resin - 10-25% or 0.5% podofilox solution or gel (Condylox)
  • Imiquimod 5% cream (Aldara) - 3 times per week, up to 4 months (A recent article reported that the optimal duration of use for women's genital warts may be 1 month.)²
  • Interferon, intramuscular or intralesional injection - 3 million units, 3 times per week for 3 weeks
  • Notably, a vaccine against HPV types 6, 11, 16, and 18 (Gardasil, Merck) has been approved by the US Food and Drug Administration as the first vaccine against HPV infection. Another vaccine against HPV types 16 and 18 (GlaxoSmithKline) will probably be available in 2006.³

Surgical Care

• Cryosurgery is very effective for treating multiple, small, genital warts.
• • Warts on the shaft of the penis and vulva respond very well to cryotherapy.
  • Cryotherapy of the rectum is painful and less successful.
  • Cryotherapy is effective and safe for the mother and fetus when used during the second and third trimesters of pregnancy.
• Electrosurgery is quite effective for a limited number of lesions on the shaft of the penis.
• • Large, unresponsive lesions around the rectum or vulva can be treated with scissor excision of the bulk of the mass followed by electrocautery of the remaining tissue down to the skin surface.
  • Loop electrocautery excisional procedure (LEEP) after colposcopic biopsy has become a standard procedure for cervical lesions particularly for the ones with neoplastic features.
  • Removal of a very large mass of warts is a painful procedure, best performed under either general or spinal anesthesia.
• Carbon dioxide laser is an efficient method of treating primary and recurrent anogenital warts because of its precision and rapid healing without scarring.
• • Primary cure rates as high as 91% have been reported.
  • Carbon dioxide laser is the treatment of choice for pregnant women with extensive lesions or lesions that do not respond to TCA.
• Pulsed-dye laser and other new lasers have been used by some with various successful rates.
• Surgery is indicated particularly for large GWs or malignant lesions.
• For recurrent carcinoma, Mohs surgery is a good choice.

Consultations

• Dermatologist
• Gynecologist
• Surgeon

MEDICATION

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Historically, medical treatments have been destructive in nature, although recently immunomodulators have been introduced.

Drug Category: Keratolytic agents

Cause cornified epithelium to swell, soften, macerate, and then desquamate.

Drug Category: Immunomodulators

Stimulate the release of key factors that regulate the immune system.

Drug Category: Interferons

Are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons may be given topically, systemically, and intralesionally.

Drug Category: Antimetabolites

Inhibit cell growth and proliferation.

Drug Category: Vaccines

An HPV vaccine is now available for prevention of HPV-associated dysplasias and neoplasia, including cervical cancer, GWs (condyloma acuminata), and precancerous genital lesions. Immunization series should be completed in girls and young women aged 9-26 y.

Drug Category: Miscellaneous topical ointments

Topical product that has gained FDA approval for GWs.

FOLLOW-UP

Section 8 of 11  

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Further Outpatient Care

• Patients typically are monitored on a periodic basis to assess for efficacy of treatment, unwanted side effects, and the development of complications. Outpatient follow-up care also provides an opportunity to evaluate for other STDs and provides patient education on an ongoing basis.

Deterrence/Prevention

• A vaccine for HPV has been recently approved by the Food and Drug Administration.

Complications

• Disease complications can include progression to malignancy and transmission to other sexual contacts. In the setting of GWs active during a pregnancy delivery, there is a small risk of laryngeal papillomatosis.
• Each therapeutic modality carries its own unique set of risks. Risks of individual medical options are enumerated above.
• Expected effects of cryosurgery include pain, edema, vesicles, bullae, weeping, and some necrosis. There is a small risk of infection, bleeding, abnormal scarring, pigment alteration, paresthesias, and alopecia with cryosurgery.
• Similarly, laser surgery of GWs may result in pigment alteration, abnormal scarring, and infection. Special care must be taken to prevent respiratory infection from the laser plume generated by vaporization of virally infected tissue.

Prognosis

• Prognosis is good, and most cases of GWs are amenable to treatment.
• Patients who are immunosuppressed with GWs may represent a special challenge.

Patient Education

• STD counseling and evaluation of partners
• • Patients with GWs deserve a focused history and physical with appropriate testing to assess for other STDs.
  • • In a population study, 7% of men and 31% of women who had GWs had concurrent STDs. In fact, 28% of these men and 71% of women had other STDs before or after their GWs.
    • Several consort studies documented that 30% of female consorts and 80% of male consorts had HPV infection. Usually, the same type of HPV involved both parties, and often they were HPV 6, 11, 16, and 18.
  • The benefit of evaluating sex partners of patients with GWs has been apparent.
• For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center. Also, see eMedicine's patient education article Genital Warts.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• Failure to diagnosis GWs correctly can result in considerable morbidity. Confusing condyloma lata for GWs will miss the diagnosis of syphilis and will lead to inappropriate therapy. Confusing pearly penile papules or Fordyce spots with GWs will result in unnecessary treatment and likely unwarranted psychosocial concern. Missing a diagnosis of verrucous carcinoma or squamous cell carcinoma is likely to delay appropriate therapy and may lead to unneeded morbidity, even mortality.
• Treatment of GWs can be difficult and lengthy. Patient expectations should be set appropriately. Patients should be counseled on their risk of infectivity to others. They also should be advised of their increased risk of having acquired other STDs.
• Each therapy of GWs has a unique set of potential adverse effects. Patients should be appropriately aware of potential adverse consequences of therapy.

Special Concerns

• Increased risk of anogenital malignancy
• • Patients with GWs have an increased risk of anogenital malignancy.
  • Infection with HPV is the primary cause of cervical malignancy, although most patients with HPV-infected cervices have a benign outcome. This mandates that female patients with GWs should have an annual screening examination and Papanicolaou test. Up to 90% of cervical cancers are caused by HPV infection of the cervix.
  • Strong epidemiologic evidence suggests that 10% of patients who had a high-grade squamous intraepithelial lesion (HGSIL, which includes so-called moderate-to-severe dysplasia, carcinoma in situ, and cervical intraepithelial neoplasia II and III) would have persistence of lesions that eventually would progress to invasive cancer without treatment. Patients with perianal warts, patients who are HIV positive, and those with a history of receptive anal intercourse are at increased risk for anal HGSIL. No direct evidence suggests that this would progress to invasive anal cancer, as lesions of the cervix are capable of doing. Nonetheless, penile, vulvar, vaginal, ovarian, and anal carcinomas have been linked to HPV infection.
• Anogenital warts in children
• • Anogenital warts are rare in the general pediatric population.
  • More than one half of children with anogenital warts have a manifestation either of viral inoculation at birth or of incidental spread of cutaneous warts. Such cases often are caused by nongenital HPV types.
  • Diagnosis of GWs in a child requires that the clinician report suspected abuse to begin an evaluation process that may or may not confirm sexual abuse.^{4, 5}
• Laryngeal papillomatosis of neonates and infants
• • Although childhood laryngeal papillomas frequently are acquired from condyloma of the mother (HPV types 6 and 11 are frequently cited), most infants of mothers with condyloma do not contract laryngeal papillomas.
  • Accordingly, cesarean delivery should not be performed solely to prevent transmission of HPV infection to the newborn.
  • Route of transmission in pregnancy is not known, and infants born by cesarean delivery have developed laryngeal papillomatosis. However, it is advisable to remove visible lesions during pregnancy.
• Patients who are immunosuppressed: Patients who are immunosuppressed such as those with AIDS and those on immunosuppressive therapy (eg, patients with renal transplants) are more likely to develop persistent HPV infection and subsequent dysplasia and malignancy.
• Verrucous carcinoma of genitalia (giant condyloma of Buschke-Löwenstein): It is a low-grade, locally invasive, squamous cell carcinoma that is associated with HPV types 6 and 11 and should be considered in the differential of lesions measuring greater than 1 cm in diameter. Only radical surgical extirpation is considered appropriate treatment.

MULTIMEDIA

Section 10 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Condyloma acuminatum.
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Media file 2:  Small papilloma of the vulva.
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Media file 3:  "Cauliflower" condyloma of the penis.
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Media file 4:  Small papilloma on the shaft of penis.
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Media file 5:  Small papilloma of the anus.
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REFERENCES

Section 11 of 11

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1. de Villiers EM. Papillomavirus and HPV typing. Clin Dermatol. Mar-Apr 1997;15(2):199-206. [Medline].
2. Garland SM, Waddell R, Mindel A, Denham IM, McCloskey JC. An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women. Int J STD AIDS. Jul 2006;17(7):448-52. [Medline].
3. Harper DM. Are we closer to the prevention of HPV-related diseases?. J Fam Pract. Jul 2005;Suppl HPV Prevention:S10-6; quiz S23. [Medline].
4. American Academy of Dermatology. Genital warts and sexual abuse in children. American Academy of Dermatology Task Force on Pediatric Dermatology. J Am Acad Dermatol. Sep 1984;11(3):529-30. [Medline].
5. Beutner KR, Reitano MV, Richwald GA, Wiley DJ. External genital warts: report of the American Medical Association Consensus Conference. AMA Expert Panel on External Genital Warts. Clin Infect Dis. Oct 1998;27(4):796-806. [Medline].
6. Beutner KR, Wiley DJ, Douglas JM, Tyring SK, Fife K, Trofatter K, et al. Genital warts and their treatment. Clin Infect Dis. Jan 1999;28 Suppl 1:S37-56. [Medline].
7. Chuang TY. Condylomata acuminata (genital warts). An epidemiologic view. J Am Acad Dermatol. Feb 1987;16(2 Pt 1):376-84. [Medline].
8. Chuang TY, Perry HO, Kurland LT, Ilstrup DM. Condyloma acuminatum in Rochester, Minn, 1950-1978. II. Anaplasias and unfavorable outcomes. Arch Dermatol. Apr 1984;120(4):476-83. [Medline].
9. Chuang TY, Perry HO, Kurland LT, Ilstrup DM. Condyloma acuminatum in Rochester, Minn., 1950-1978. I. Epidemiology and clinical features. Arch Dermatol. Apr 1984;120(4):469-75. [Medline].
10. Fitzpatrick T, Eisen A, Wolff K. Fitzpatrick T, Goldsmith L, Austen K, et al, eds. Dermatology in General Medicine. 5^th ed. New York, NY: McGraw-Hill; 1999:1371-2, 1390-1, 2484-97, 2550, 2986.
11. Habif TP. Clinical Dermatology: A Color Guide to Diagnosis and Therapy. 3^rd ed. St. Louis, Mo: Mosby; 1995:297-302.
12. Koutsky L. Epidemiology of genital human papillomavirus infection. Am J Med. May 5 1997;102(5A):3-8. [Medline].
13. Nebesio CL, Mirowski GW, Chuang TY. Human papillomavirus: clinical significance and malignant potential. Int J Dermatol. Jun 2001;40(6):373-9. [Medline].
14. Rhea WG Jr, Bourgeois BM, Sewell DR. Condyloma acuminata: a fatal disease?. Am Surg. Nov 1998;64(11):1082-7. [Medline].
15. Simms I, Fairley CK. Epidemiology of genital warts in England and Wales: 1971 to 1994. Genitourin Med. Oct 1997;73(5):365-7. [Medline].
16. Tortolero-Luna G. Epidemiology of genital human papillomavirus. Hematol Oncol Clin North Am. Feb 1999;13(1):245-57, x. [Medline].

Article Last Updated: Feb 1, 2007