Introduction
Condylomatous warts of the genital tract and anus have been described as early as the first century AD. The venereal origin of the disease was described in the 1950s. Intracellular virus particles in the wart tissue were demonstrated in 1968. In the 1970s, further work attributed these cellular changes to human papillomavirus (HPV) infection. Simultaneously, molecular hybridization techniques demonstrated the genetic heterogeneity of HPVs.
In the following decades, nearly 100 HPVs were identified by polymerase chain reaction (PCR)–based assays, and the genomes of about 75 HPVs were cloned and sequenced.1 Of these, more than 30 types infect the genital tract. Recent epidemiologic and molecular studies have conclusively shown the association of HPV types with the development of genital tract and anal cancers.
Problem
Genital and urethral warts are caused by HPV and are easily spread by sexual contact. Subtype HPV 6 is most frequently detected in genital warts. Most of the newly acquired genital HPV infections are subclinical and asymptomatic. Occasionally, the detection of HPV DNA in genital specimens may be the only evidence of current infection. Furthermore, serum antibodies to specific HPV types may be the only indication of past exposure. After a long period of latency, individuals infected with certain HPV subtypes are at risk of developing squamous cell carcinomas.2 Immunosuppression is associated with reactivation of HPV, increasing the risk of malignant transformation.
The epidemiologic extent of this disease was underestimated until recent advances in PCR-based assays and DNA hybridization techniques enabled the identification of people who are asymptomatic and infected. In 1991, a study by Bauer et al utilized PCR techniques and demonstrated that 46% of college women undergoing routine pelvic examination were infected with HPV.3 HPV infection is now considered the principal etiologic agent in cervical dysplasia and cervical cancer. HPV 16 has been associated with more than 50% of cervical malignancies. Condylomata have also been linked with squamous cell carcinoma of the penis.
With increased recognition of the problem and better detection methods, the number of patient visits to physicians' offices for genital warts has steadily increased since the 1950s. In the United States, an 8-fold increase in the age- and sex-adjusted incidence of genital warts was reported from 1950-1954 and 1975-1978. A 4.5-fold increase in the number of first consultations for genital warts occurred from 1966-1984.
Current evidence suggests that more than 50% of sexually active adults have been infected with one or more genital HPV types, most of which are subclinical, unrecognized, and benign. This is presently considered a minor sexually transmitted disease (STD) and not reportable, but the asymptomatic nature of the condition and its potential association with malignancy require a high degree of diligence in its diagnosis and management in patients who are at risk.
In a recent study screening high-risk individuals such as asymptomatic male partners of females with HPV infection, even though they were clinically free of genital warts, 20.3% tested positive for HPV DNA using the hybrid capture 2 (HC2) microplate assay.4
Frequency
- United States: Genital warts affect approximately 500,000-1 million patients annually. Approximately 5% of these patients have urethral warts. Recent PCR-based studies detected HPV DNA in 12-16.5% of urethral specimens from healthy young volunteers.
- International: The incidence is similar to that reported in the United States.
Etiology
Urethral warts are caused by HPV. They are primarily sexually transmitted, and transmission is possibly enhanced by the moisture and abrasion of epithelial surfaces. The risk of genital infection increases with each new sex partner. Condoms are not definitely known to provide an effective barrier. Nonsexual transmission through fomites is significant for skin warts but not known in genital warts. Blood-borne transmission has not been reported. Perinatal transmission accounts for cases of condylomata found during the first week of life. Urethral instrumentation such as in cystoscopy or repeated urethral dilatation in patients with pre-existing genital HPV infection has been shown to cause dissemination of HPV into the proximal urethra.5
HPV is a DNA virus with several characterized subtypes (see Human Papillomavirus).6 Viral types 6,11, 42-44, and 54 are associated with condylomata acuminata and low-grade dysplasia, while types 16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 66, and 68 have a higher association with genital malignancy (especially cervical malignancy). HPV co-infection is also facilitated by immunosuppressed states such as HIV and AIDS. PCR-based methods have shown HPV prevalence rates of 41-74% in women who are HIV seropositive.
Pathophysiology
Cells infected with HPV divide rapidly with duplication of viral particles. These epitheliotropic viruses depend on differentiating squamous epithelium for their replication. Viral capsid proteins and infectious viruses are found in the superficial differentiated cell layers. The disease is transmitted when the viral particles released from the lesions come into contact with another person. Approximately two thirds of the sexual contacts of patients with genital warts develop the same disease. Incubation periods are usually 1-2 months but may extend to several months.
Presentation
A significant proportion of affected men and women are asymptomatic, and their subclinical lesions are not identifiable by simple inspection. When present, the warty lesions are located in moist mucocutaneous surfaces of the perineal and genital areas. A few patients complain of associated symptoms of itching, burning, pain, or bleeding; women may notice a vaginal discharge. Warts occur either singly on a stalk or in broad-based clusters and are soft and friable.
In males, the glans penis, shaft, and prepuce are common sites of infection. Urethral warts are mostly found in the meatus and fossa navicularis but may extend as far as the prostatic urethra. In females, the vulva, vagina, and cervix are common sites of infection. Lesions are also observed at the anal verge and occasionally in the mouth. Bladder involvement is rare.
Generally, condylomata appear in areas subject to physical trauma occurring during sexual intercourse. They may spread to adjacent areas by autoinoculation. Morphologic types include (1) larger cauliflowerlike condylomata, (2) flesh-colored, dome-shaped papular warts that are 1-4 mm in diameter, (3) keratotic warts with a thick crustlike layer resembling skin warts; and (4) flat-topped macular warts. Regional lymph nodes are not enlarged.
Suspect urethral warts when patients with genital warts present with pyuria or urethral discharge. Intraurethral warts may be a cause of recurrent meatal warts. Urethral and bladder involvement with condylomata is often associated with immunosuppression. Gay men who are HIV positive and who practice receptive anal intercourse may present with anal and intra-anal warts. Other groups of immunosuppressed persons (eg, people receiving transplants, people with Hodgkin disease, people with AIDS, people with diabetes) may develop perianal lesions but not intra-anal warts, which are due to transfer of the virus inside the anus.
Carefully assess the external genitalia of patients presenting with a typical sexual history and symptoms suggestive of urethral involvement. Include investigations to exclude other concomitant STDs. Offer current sexual partners of the patients an examination and treatment for macroscopically visible warts and other STDs. If screening of male partners is to be offered, specimens obtained from penile and urethral brushing for HPV DNA detection appear to be the most accurate.7 Semen may be alternative to urethral brushing.
Contraindications
Medical treatments aimed at treating urethral warts should generally be used with caution, and they should be used only when the warts are easily accessible, as in the fossa navicularis.
Podophyllin is contraindicated during pregnancy.
More on Urethral Warts |
 Overview: Urethral Warts |
| Workup: Urethral Warts |
| Treatment: Urethral Warts |
| Follow-up: Urethral Warts |
| References |
| Further Reading |
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References
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Keywords
urethral warts, genital warts, condylomatous warts, venereal warts, genital condyloma, condyloma acuminatum, sexually transmitted diseases, STDs, human papillomavirus, HPV, squamous cell carcinomas, SCCs, cervical dysplasia, cervical cancer, sexually transmitted infections, STIs
