|December 2011 · Vol. 23, No. 12
External Genital and Perianal Warts: Disease Characteristics
Program Chairperson, Past-President, American Society, for Colposcopy and Cervical Pathology, (ASCCP), Director, Women’s Clinic Student Health Center (Retired), University of California, Santa Barbara, Santa Barbara, CA
Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Alabama at Birmingham, Senior Scientist, UAB Comprehensive Cancer Center, Birmingham, AL
Professor, Family Medicine, Professor, Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA
Obstetrician and Gynecologist, Private Practice, Department of Obstetrics and Gynecology, Northside Hospital, Atlanta, GA
Clinical Professor, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, CA
J. Thomas Cox, MD, is a consultant to Gen-Probe and Roche and is a member of the Speakers Bureau for GlaxoSmithKline, PharmaDerm, Graceway Pharmaceuticals, and BD Diagnostics. He has received financial/ material support from Merck, HPV Vaccine Data and Safety Monitoring Board.
Warner Huh, MD, has received grant/research support from Merck, GlaxoSmithKline, and Roche. He is a consultant for Roche, Helix, BioPharma, Qiagen, Hologic, and Inovio.
E. J. Mayeaux, Jr, MD, is a consultant and serves on the Speakers Bureau for PharmaDerm and Merck.
Michael Randell, MD, is a consultant and serves on the Speakers Bureau for Alaven Pharmaceuticals, Cord Blood Registry, Intuitive Surgical, Merck, Myriad Genetics, OmniGuide, PharmaDerm, Qiagen, Quest Diagnostics, SurgiQuest, Teva Pharmaceuticals, Vermillion, and Watson Pharmaceuticals.
Maida Taylor, MD, is a consultant for Everett Labs, Semprae Labs, ChemoSpain, PharmaDerm, Depomed, and Boehringer Ingelheim. This roundtable meeting and supplement were supported by PharmaDerm, A Division of Nycomed US Inc.
This roundtable meeting and supplement were supported by PharmaDerm, A Division of Nycomed US Inc.
The authors wish to thank Mary Tom, PharmD, and Malik Cobb, PA-C, for their medical writing and editorial assistance.
External genital and perianal warts (EGW) are diagnosed in more than 1 million new patients in the United States each year, and may be associated with substantial individual and societal burden
EGW are caused by sexually transmitted human papillomavirus (HPV) types, with HPV 6 and 11 being responsible for about 90% of EGW
The time between exposure to HPV and the development of EGW varies, with some cases occurring within 2 to 3 weeks of exposure and others only after several months or years
EGW have high rates of spontaneous viral clearance and disease regression; however, the time to clearance varies greatly and most individuals with EGW prefer to treat them to hasten resolution
External genital and perianal warts (EGW) are increasingly common in the United States, with more than 1 million new cases diagnosed each year, predominantly among women.1,2 The impact of EGW may be substantial for the individuals who contract the disease and for society. For individuals, particularly women, a diagnosis of EGW may provoke psychological and emotional distress.3,4 The impact to society may be considerable, with associated costs of new cases estimated to be $171 million annually.5
External genital and perianal warts are a major clinical consequence of one of the most commonly acquired sexually transmitted diseases (STDs): human papillomavirus (HPV) infection.1 An estimated prevalence in the US population indicates that 15% of adults are currently infected with HPV.6 In the year 2000, there were an estimated 6.2 million new HPV infections in the United States, with the majority (74% [4.6 million]) occurring among young Americans (15- to 24-year-olds).7 The rise in the number of patients identified with HPV disease may be attributed to increased awareness of the various manifestations of HPV disease and the increased use of HPV DNA testing.8 Whereas more than 150 HPV types have been characterized,9 90% of genital and perianal warts are associated with HPV types 6 and 11.10-12
The process by which HPV infects and replicates is summarized in Figure 1.11,13 Briefly, HPV typically gains entry into the epithelium through sites of microabrasion from trauma, or areas naturally thin, such as the transformation zones of the cervix and anus, and infects basal keratinocytes. After a period of latency, viral DNA replication occurs in differentiating cells. As the keratinocytes mature in the upper layers of the epithelium, viral assembly of a protein capsule surrounding the DNA core creates an infective unit; the shedding of this rekindles the process of transmission and release. Because HPV does not kill its host cell, lysis of HPV-infected epithelial cells and release of viral antigen to be detected by the immune system do not typically occur in the absence of trauma or treatment. Throughout this entire process, HPV remains sequestered within the epithelium. HPV is cleared via a cell-mediated immune response, allowing it to evade the host’s natural immune system and limiting the innate immune response.
The time between exposure to HPV and the development of EGW varies, with some cases occurring within 2 to 3 weeks of exposure and others only after many more months or years (median 2.9 months).14 Many HPV infections are mild and transient and, with an effective immune response, will eventually resolve or regress spontaneously.6 However, even with treatment, the median time to resolution is 5.9 months from beginning therapy.14
A number of risk factors for HPV infectivity has been identified and includes recent change in sex partner(s), a high number of sexual partners, previous infection with herpes simplex, past history of genital warts, early age at first sexual intercourse, compromised immune status, and young age (<25 years).6,10 A recent study demonstrated that the incidence of high-risk HPV infection dramatically increases with the number of current and concurrent sex partners.15
CLINICAL PRESENTATION AND DIAGNOSIS
External genital and perianal warts are generally asymptomatic, but may be uncomfortable or slightly pruritic.2,10,16 They manifest as solitary or clustered keratotic plaques and papules on well-keratinized skin, such as the vulva, perianus, and penis, or minimally keratinized lesions on modified mucosa, such as the introitus.1,10,16 They are often exophytic and cauliflower-shaped, but may also be flat, papular, keratotic, or frond-like, and the color may vary (flesh-colored, white, gray, or pigmented). Many EGW are visible to the naked eye; therefore, diagnosis is made by visual inspection6; however, for smaller lesions, the diagnosis may be aided by bright light and magnification.1 External genital and perianal warts, especially in younger patients, have high rates of viral clearance and disease regression—as many as 30% over 4 months and approximately 90% will clear within 2 years.11,17 The rate of long-term regression is currently unknown.17
External genital and perianal warts are a common consequence of HPV infection that impacts individuals and society. Clinical presentation may vary; however, most EGW are visible to the naked eye and can be diagnosed by visual inspection. Although some EGW may clear spontaneously, the time to clearance varies greatly and most individuals with EGW prefer to treat them to hasten clearance. Certainly, persistent disease may require treatment.
The roundtable meeting and this supplement were supported by PharmaDerm, A Division of Nycomed US Inc.
Veregen® (sinecatechins) Ointment, 15% is a topical ointment indicated for the treatment of external genital and perianal warts (Condylomata acuminata) in immunocompetent patients 18 years of age or older.
VEREGEN® has not been evaluated to treat urethral, intra-vaginal, cervical, rectal, or intra-anal human papilloma viral disease and should not be used to treat these conditions. Avoid use of VEREGEN® on open wounds.
Avoid exposure of VEREGEN®-treated areas to sun/UV-light because VEREGEN® has not been tested under these circumstances. Safety and efficacy of VEREGEN® have not been established in immunosuppressed patients or patients under 18 years of age, or for the treatment of external genital and perianal warts beyond 16 weeks or for multiple treatment courses.
The most common adverse reactions are local skin and application site reactions including (incidence ≥ 20%) erythema, pruritus, burning, pain/discomfort, erosion/ulceration, edema, induration, and vesicular rash.
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2. Mayeaux EJ, Dunton C. Modern management of external genital warts. J Low Genit Tract Dis. 2008;12(3):185–192.
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6. Centers for Disease Control and Prevention. Human papillomavirus: HPV information for clinicians. Atlanta, GA: Centers for Disease Control and Prevention, US Dept of Health and Human Serivces; April 2007.
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8. Gearhart PA, Randall TC, Buckley RM Jr. Human papillomavirus. Medscape Reference Web site. http://emedicine.medscape.com/article/219110-overview#showall. Published April 15, 2011. Accessed April 27, 2011.
9. National Cancer Institute. Fact sheet. Human papillomaviruses and cancer. http://www.cancer.gov/cancertopics/factsheet/risk/hpv#r1. Reviewed December 13, 2010. Accessed March 29, 2011.
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12. Garland SM, Steben M, Sings HL, et al. Natural history of genital warts: analysis of the placebo arm of 2 randomized phase III trials of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine. J Infect Dis. 2009;199(6):805–814.
13. Kahn JA. HPV vaccination for the prevention of cervical intraepithelial neoplasia. N Engl J Med. 2009;361(3):271–278.
14. Winer RL, Kiviat NB, Hughes JP, et al. Development and duration of human papillomavirus lesions, after initial infection. J Infect Dis. 2005;191(5):731–738.
15. Javanbakht M, Gorbach PM, Amani B, et al. Concurrency, sex partner risk, and high-risk human papillomavirus infection among African American, Asian, and Hispanic women. Sex Transm Dis. 2010;37(2):68–74.
16. Workowski KA, Berman S. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Morb Mortal Wkly Rep. 2010;59(RR-12):70–74.
17. Scheinfeld N, Lehman DS. An evidence-based review of medical and surgical treatments of genital warts. Dermatol Online J. 2006;12(3):5.
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