Condylomata Acuminata – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Description

Condylomata acuminata are soft, skin-colored, fleshy warts that are caused by human papillomavirus (HPV):

  • HPV types 6, 11, 16, 18, 31, 33, and 35 associated with condylomata acuminata
  • Highly contagious; incubation period may be from 1–6 months.
  • Warts appear singly or in groups, small or large; on the vagina, cervix, around the external genitalia and rectum, and in the urethra and anus. Reports of conjunctival, nasal, oral, and laryngeal warts and occasionally the throat.
  • System(s) affected: Skin/Exocrine; Reproductive

Pediatric Considerations

Consider sexual abuse if seen in children, although they can be infected by other means (e.g., transfer from wart on another child’s hand).

Pregnancy Considerations

  • Warts often grow larger during pregnancy and regress spontaneously after delivery. Use cryotherapy.
  • Virus does not cross the placenta. Treatment during pregnancy is somewhat controversial. Cesarean section is not absolutely indicated.
  • Few documented cases of HPV transmission to infant at time of delivery have resulted in laryngeal papillomas, a rare and life-threatening condition.
  • HPV vaccination is contraindicated in pregnancy.

Epidemiology

  • Most common viral sexually transmitted infection (STI) in the US
  • Predominant age: 15–30 years old
  • Predominant sex: Male = Female

Incidence

  • Venereal warts are increasing in an ever-younger population. A recent study of 487 college women showed an infection rate of 48%.
  • Increased size and number in immunocompromised patients

Prevalence

  • Peak prevalence in ages 17–33
  • Minimum of 10–20% of sexually active women may be infected with HPV. Studies in men suggest a similar prevalence.
  • Pregnancy and immunosuppression favor recurrence and increasing growth of lesions.

Risk Factors

  • Young adults and adolescents
  • Multiple sexual partners
  • Not using condoms
  • Possibly subclinical infection
  • Young age of commencing sexual activity
  • Cigarette smoking: Tobacco smoke has been shown to reduce cellular protection by decreasing cervical keratinocyte production.
  • Poor hygiene
  • History of genital warts

General Prevention

  • Use of condoms (preventive effects not adequately evaluated; 40% of infected men have scrotal warts)
  • Abstinence until treatment completed
  • Circumcision may prevent recurrence in some men.
  • Quadrivalent HPV vaccine available against genital warts and cervical cancer. This vaccination is targeted to adolescents before the period of their greatest risk for exposure to HPV. The vaccine does not treat previous infections:
    • Immunity has been documented to last at least 5 years after HPV vaccination.
    • The use of 4 HPV-specific virion protein capsids address the 2 most common HPV serotypes to be contracted in 6 and 11, and the 2 most cancer-promoting types in 16 and 18 (Gardasil) (1,4).
    • HPV quadrivalent vaccine protects against some types of condyloma-producing virus.
    • Quadrivalent vaccine, females and males (1) ages 9–26: Vaccine is administered IM; 3 doses to achieve optimal seroconversion.
    • Vaccination regimen: 0.5 mL IM injection first dose, and at months 2 and 6 after first dose to complete vaccination.
    • Observe recipients of vaccine for syncopal response.
  • Bivalent HPV vaccine is available but does not cover the common viruses that cause condyloma lesions (Cervarix) (2).

Etiology

HPV is a circular double-stranded DNA molecule. There are >70 HPV subtypes. Types 6 and 11 cause common venereal warts. Cervical dysplasia and carcinoma in situ associates with types 16, 18, 31, 33, and 35.

Commonly Associated Conditions

  • >90% of cervical cancer associated with HPV
  • STIs (i.e., gonorrhea, syphilis, chlamydia); AIDS

Human papillomavirus, Sexually transmitted disease, Genital wart, HPV vaccine, HPV, Gardasil, external genitalia, laryngeal papillomas, sexual abuse,

Diagnosis

History

Explore sexual history, contraception use, and other lifestyle issues.

  • Pruritus
  • Vaginal discharge
  • Irritation (burning and redness)

Physical Exam

  • Multiple fingerlike projections; soft, sessile; smooth or rough
  • Perianal condylomata acuminata usually rough and cauliflower-like
  • Male sites include frenulum, corona, glans, prepuce, meatus, shaft, and scrotum.
    • Penile lesions often smooth and papular; occur in groups of 3 or 4
  • Female sites include labia, clitoris, periurethral area, perineum, vagina, and cervix (flat lesions).
  • Bleeding (result of trauma)
  • Perianal area (both sexes)

Diagnostic Tests & Interpretation

Acetowhitening test: Subclinical lesions can be visualized by wrapping the penis with gauze soaked with 5% acetic acid for 5 minutes. Using a 10× hand lens or colposcope, warts appear as tiny white papules. A shiny white appearance of the skin represents foci of epithelial hyperplasia (subclinical infection); not highly specific, low positive predictive value.

Lab

  • Serologic tests for syphilis negative
  • Pap smear

Diagnostic Procedures/Surgery

Biopsy with highly specialized identification techniques rarely useful. HPV DNA detected through polymerase chain reaction

  • Colposcopy
  • Antroscopy, anoscopy, urethroscopy may be required

Pathological Findings

  • Possible cervical dysplasia
  • Sometimes difficult to differentiate from squamous cell carcinoma

Differential Diagnosis

  • Condylomata lata (flat warts of syphilis)
  • Lichen planus
  • Normal sebaceous glands
  • Seborrheic keratosis
  • Molluscum contagiosum
  • Keratomas, micropapillomatosis
  • Scabies
  • Crohn disease
  • Skin tags
  • Melanocytic nevi
  • Vulvar intraepithelial neoplasia
  • Buschke-Lowenstein tumor

Treatment

Medication

First Line

  • Imiquimod (Aldara): self-treatment with a 5% cream applied overnight 3 times weekly until warts resolve for up to 16 weeks. The skin is then washed with soap and water 6 to 10 hours after application (3,2)
    • Precautions: Imiquimod has been noted to weaken condoms and diaphragms; therefore, patients should refrain from sexual contact while the cream is on the skin (3).
  • Cryotherapy: Liquid nitrogen is applied to warts for 2 5- to 10-second bursts; usually requires 2–3 weekly sessions (3,5).
  • Podophyllin in tincture of benzoin. Apply directly to warts. Leave on for 1–4 hours, then wash off. Repeat treatment every 7 days until gone (in-office procedure) or (3,6)
  • Podofilox (Condylox): Apply to external warts (affected area) every 12 hours (allowing to dry) for 3 consecutive days. May repeat after 4 days (home application) (3,6).
  • Trichloroacetic acid: 25–85%. Apply only to warts. Use powder/talc to remove unreacted acid. Repeat in office at weekly intervals.
  • Trichloroacetic acid is ideal for isolated lesions in pregnant women.
  • Intralesion interferon has been shown to be effective in refractory cases and should be reserved for such cases (7,8).
  • Oral:
    • Oral cimetidine: 30–40 mg/kg divided t.i.d. for 3 months in children with genital and perigenital condyloma. It is used as a primary and adjunctive therapy (9).
  • Contraindications:
    • Podophyllin: Do not use in pregnant patients or on oral, cervical, urethral, or perianal warts. Can use on limited number of vaginal warts with careful drying after application. It is recommended that no more than 0.5 mL should be used.
    • Cryotherapy: Cryoglobulinemia
  • Precautions:
    • Podophyllin: To minimize local and systemic reactions, wash treated areas 1–4 hours after application and use ointments to protect surrounding skin from contact with podophyllin.
    • Cryotherapy: None
    • Electrocautery: Do not use in patients with pacemaker.

Second Line

  • External (penile and perianal):
    • Podophyllin (3)
    • Podofilox (Condylox) self-treatment (3)
    • Intralesional interferon
    • Small study of topical use of Calmette-Guérin bacillus for penile lesions (10)
    • Cidovir 1% topical applied once daily for 5 contiguous days per week for 6 cycles (11)
  • Urethral meatus:
    • Podophyllin (3)
    • Cryrotherapy (3,5)
    • Topical fluorouracil is no longer recommended due to severe side effects and teratogenicity. However, for refractory cases intralesional injection with fluorouracil/epinephrine/bovine collagen gel has been proven effective in phase clinical trials (12).
  • Anal:
    • Trichloroacetic acid: Apply weekly (13).
    • Topical fluorouracil is no longer recommended.
  • Uterine/cervix
    • Trichloroacetic acid and Cryrotherapy are treatment options (3).
    • Oral isotretinoins can be used for the treatment of recalcitrant condyloma acuminata of the cervix (note special prescription monitoring for this class of medications) (14).

Additional Treatment

Pregnancy Considerations

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  • Podophyllin, podofilox, and fluorouracil should not be used in pregnancy due to the concern of possible teratogenicity (3).
  • Surgical excision, trichloroacetic acid, Cryotherapy, and electrocautery are treatment options during pregnancy to minimize neonatal exposure to the virus (3).

General Measures

  • May resolve spontaneously
  • Change therapy if no improvement after 3 treatments, no complete clearance after 6 treatments, or therapy’s duration or dosage exceeds manufacturer’s recommendations.
  • Appropriate screening/counseling of partners

Surgery/Other Procedures

  • Larger warts require laser treatment or electrocoagulation including infrared therapy (15)
    • Precaution: Laser treatment may create smoke plumes that may contain HPV; therefore, it is recommended that physicians performing this procedure should wear appropriate masks.
  • Surgical excision for large warts
  • Intraurethral, external (penile and perianal), anal, and oral lesions can be treated with fulgurating CO2 laser. Oral or external penile/perianal lesions can also be treated with electrocautery or surgery (3).

Ongoing Care

Follow-Up Recommendations

No restrictions, except for sexual contact

Patient Monitoring

  • Patients seen every 2 weeks until lesions resolve and have annual Pap test
  • Patients should also follow up 3 months after completion of treatment
  • Persistent warts require biopsy.
  • Sexual partners require monitoring.
  • Treatment does not decrease transmissible infectivity.

Patient Education

  • Provide pamphlets on HPV, STI prevention, and condom use.
  • Emphasize the need for women to get regular Pap smears.

Prognosis

  • Warts will clear with treatment or resolve spontaneously, but recurrences are frequent and may necessitate repeated treatment.
  • Some studies identified 3 independent risk factors for condylomatous relapse: Positive HIV status, male gender, and Langerhans cell level: Cell level per millimeter of anal tissue (15 vs. 30)
  • Without treatment, may remain stable, worsen, or resolve completely
  • Asymptomatic infection persists indefinitely.

Complications

  • Cervical dysplasia
  • Malignant change: Progression to cancer rarely, if ever, occurs.
  • Male urethral obstruction
  • The prevalence of high-grade dysplasia and cancer in anal canal is higher in HIV-positive than in HIV-negative patients, probably because of HPV activity.

References

1. Centers for Disease Control and Prevention (CDC) et al. FDA licensure of quadrivalent human papillomavirus vaccine (HPV4, Gardasil) for use in males and guidance from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2010;59:630–2.

2. Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent human papillomavirus vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep.2007;56(RR-2):1–24.

3. Charles M, Kodner MD, Soraya Nasraty MD. University of Louisville School of Medicine, Louisville, Kentucky. Am Fam Physician. 2004;70(12):2335–2342.

4. Edwards L. Imiquimod in clinical practice. Aust J Dermatol.1998;39(Suppl 1):S14–S16.

5. Maw RD et al. Treatment of anogenital warts. Dermatol Clin.1998;16:829–34, xv

6. Lacey CJ, et al. Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts. Sex Transm Infect2003;79:270.

7. Welander CE, Homesley HD, Smiles KA, Peets EA et al. Intralesional interferon alfa-2b for the treatment of genital warts.Am. J. Obstet. Gynecol. 1990;162:348–54.

8. Klutke JJ, Bergman A. Interferon as an adjuvant treatment for genital condyloma acuminatum. Int J Gynaecol Obstet. 1995;49:171.

9. Franco I. Oral cimetidine for the management of genital and perigenital warts in children. J Urol. 2000;164:1074–5.

10. Böhle A, Büttner H, Jocham D. Primary treatment of condylomata acuminata with viable bacillus Calmette-Guerin. J Urol. 2001;165:834–6.

11. Snoeck R, Bossens M, Parent D, Delaere B, Degreef H, Van Ranst M, Noël JC, Wulfsohn MS, Rooney JF, Jaffe HS, De Clercq E et al. Phase II double-blind, placebo-controlled study of the safety and efficacy of cidofovir topical gel for the treatment of patients with human papillomavirus infection. Clin Infect Dis. 2001;33:597–602.

12. Swinehart JM, Sperling M, Phillips S, Kraus S, Gordon S, McCarty JM, Webster GF, Skinner R, Korey A, Orenberg EK. Intralesional fluorouracil/epinephrine injectable gel for treatment of condylomata acuminata. A phase 3 clinical study. Arch Dermatol.1997;133(1):67–73.

13. Sobhani I, Vuagnat A, Walker F, et al. Prevalence of high-grade dysplasia and cancer in the anal canal in human papillomavirus-infected individuals. Gastroenterology. 2001;120:857–66.

14. Georgala S, Katoulis AC, Georgala C, Bozi E, Mortakis A et al. Oral isotretinoin in the treatment of recalcitrant condylomata acuminata of the cervix: a randomised placebo controlled trial. Sex Transm Infect. 2004;80:216–8.

15. Bekassy Z, Weström L et al. Infrared coagulation in the treatment of condyloma acuminata in the female genital tract. Sex Transm Dis. 1987;14:209–12.

Additional Reading

Beutner KR, Spruance SL, Hougham AJ, et al. Treatment of genital warts. J Am Acad Dermatol 1998;38:230.

17. Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006;55:1–94.

Codes

ICD9

078.11 Condyloma acuminatum

Snomed

240542006 Anogenital warts (disorder)

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