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Consider sexual abuse if seen in children, although children can be infected by other means (e.g., transfer from wart on another child's hand or prolonged latency period) (2).
American Academy of Pediatrics recommends all school-aged children who present with lesions be evaluated for abuse and screened for other STDs (2).
Pregnancy Considerations
Warts often grow larger during pregnancy and regress spontaneously after delivery.
Virus does not cross the placenta. Treatment during pregnancy is somewhat controversial. Cesarean section is not absolutely indicated for maternal condylomata (3)[A].
Cervical infection has been found to be a risk factor for preterm birth (3)[A].
Few documented cases of laryngeal papillomas due to HPV transmission at the time of delivery. Although rare, the condition is life-threatening (4).
HPV vaccination is contraindicated in pregnancy.
The safety of imiquimod, sinecatechins, podophyllin, and podofilox during pregnancy has not been established (3)[C].
EPIDEMIOLOGY
- HPV types 6 and 11 associated with 90% of condylomata acuminata. Types 16, 18, 31, 33, and 35 may be found in warts and may be associated with high-grade intraepithelial dysplasia in immunocompromised states such as HIV.
- Highly contagious; incubation period may be from 1 to 8 months. Initial infections may very well go unrecognized, so a "new"¯ outbreak may be a relapse of an infection acquired years prior.
- Predominant age: 15 to 30 years
- Predominant sex: 1:1 male to female
- Most infections are transient and clear spontaneously within 2 years.
Incidence
One study population demonstrated that from 2007 to 2010, with the introduction of HPV vaccines, the incidence of genital warts decreased 35% (from 0.94% per year to 0.61% per year) in females <21 years, and decreased 19% in males <21.
Prevalence
- Most common viral sexually transmitted infection (STI) in the United States. Most sexually active men and women will have acquired a genital HPV infection, usually asymptomatic, at some time.
- Peak prevalence in ages 17 to 33 years
- 10-20% of sexually active women may be actively infected with HPV. Studies in men suggest a similar prevalence.
- Pregnancy and immunosuppression favor recurrence and increased growth of lesions.
ETIOLOGY AND PATHOPHYSIOLOGY
HPV is a circular, double-stranded DNA molecule. There are >120 HPV subtypes. HPV types that cause genital warts do not cause anogenital cancers.
RISK FACTORS
- Usually acquired by sexual activity
- Young adults and adolescents
- Multiple sexual partners; short interval between meeting new sex partner and first intercourse
- Not using protective barriers
- Young age of commencing sexual activity
- History of other STI
- Immunosuppression (particularly HIV)
GENERAL PREVENTION
- Sexual abstinence or monogamy
- Quadrivalent HPV vaccine available against genital warts and cervical cancer. This vaccine 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 HPV quadrivalent vaccine (Gardasil) protects against the two most common HPV serotypes (types 6 and 11, which cause most anogenital warts) and the two most cancer-promoting types (16 and 18) (5).
- Quadrivalent vaccine is indicated for females and males ages 9 to 26 years: Vaccine is administered IM; 3 doses at 0, 2, and 6 months to achieve optimal seroconversion (6).
- Vaccine efficacy for preventing external genital warts is related to age of administration of 1st dose: 76% if aged <20 years, 93% if <14 years.
- Bivalent HPV vaccine is available but does not cover the HPV types that cause most condyloma lesions (Cervarix) (5).
- Quadrivalent vaccine has been proven effective in prevention of external lesions in males 16 to 26 years of age (5).
- Use of condoms is partially effective, although warts may be easily spread by lesions not covered by a condom (e.g., 40% of infected men have scrotal warts).
- Abstinence until treatment completed
COMMONLY ASSOCIATED CONDITIONS
- >90% of cervical cancer associated with HPV types 16, 18, 31, 33, and 35
- 60% of oropharyngeal and anogenital squamous cell carcinomas are associated with HPV
- STIs (e.g., gonorrhea, syphilis, chlamydia), AIDS
DIAGNOSIS
HISTORY
- Explore sexual history, contraception use, and other lifestyle topics.
- Most warts are asymptomatic but symptoms include
- Pruritus, burning, redness, pain, bleeding
- Vaginal discharge
- Large warts may cause obstructive symptoms in the anus (with defecation) or vaginal canal (with intercourse or childbirth)
PHYSICAL EXAM
- Lesions often have a typical rough, warty appearance with multiple fingerlike projections but may be soft, sessile, and smooth.
- Large lesions are cauliflower-like and may grow to >10 cm.
- Most common sites: penis, vaginal introitus, and perianal region
- May be seen anywhere on the anogenital epithelium or in the anogenital tract
- Warts often occur in clusters.
- Bleeding or irritation of the lesions may be noted.
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
- Squamous cell carcinoma
DIAGNOSTIC TESTS & INTERPRETATION
- Diagnosis is usually clinical, made by unaided visual examination of the lesions.
- Biopsy
- Acetowhitening test: Subclinical lesions can be visualized by wrapping the penis with gauze soaked with 5% acetic acid (vinegar) 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), but because of low specificity, the CDC recommends against routine use of this test to screen for HPV mucosal infection.
Initial Tests (lab, imaging)
- Usually not required for diagnosis
- Serologic tests for syphilis may be helpful to rule out condylomata lata.
- Other testing for STIs
- Pap smear may be indicated.
Follow-Up Tests & Special Considerations
Because squamous cell carcinoma may resemble or coexist with condylomata, biopsy may be considered for lesions refractory to therapy.
Diagnostic Procedures/Other
- Biopsy with highly specialized identification techniques, such as HPV DNA detected through polymerase chain reaction, is rarely useful.
- Colposcopy, antroscopy, anoscopy, and urethroscopy may be required to detect anogenital tract lesions.
- Screening men who have sex with men (MSM) with anal Pap smears is controversial.
TREATMENT
GENERAL MEASURES
- May resolve spontaneously
- Change therapy if no improvement after 3 treatments, not complete clearance after 6 treatments, or therapy's duration or dosage exceeds manufacturer's recommendations.
- Appropriate screening/counseling of partners
MEDICATION
First Line
- No single therapy for genital warts is ideal for all patients or clearly superior to other therapies.
- Recommendations for external genital warts, patient-applied:
- Podofilox (Condylox): antimitotic action; apply 0.5% solution or gel to warts twice daily (allowing to dry) for 3 consecutive days at home followed by 4 days of no therapy; may repeat up to 4 total cycles; maximum of 0.5 mL/day or area less than 10 cm2 (3)[A],(7)
- Imiquimod (Aldara): immune enhancer; self-treatment with a 5% cream applied once daily at bedtime 3 times weekly until warts resolve for up to 16 weeks. Wash off with soap and water 6 to 10 hours after application. Imiquimod has been noted to weaken condoms and diaphragms; therefore, patients should refrain from sexual contact while the cream is on the skin (3)[A],(8).
- Sinecatechins (Veregen): immune enhancer and antioxidant, extract from green tea; apply a 0.5-cm strand of ointment 3 times daily for up to 16 weeks. Do not wash off after use (3)[A].
- Recommendations for external genital warts, provider-applied:
- Cryotherapy: liquid nitrogen applied to warts for two 10-second bursts with thawing in between; usually requires 2 to 3 weekly sessions (3)[A]
- Podophyllin 10-25% in tincture of benzoin. Apply directly to warts, air-dry in office before coming into contact with clothes. Wash off in 1 to 4 hours. Repeat every 7 days in office until gone (3)[A],(7).
- Trichloroacetic acid (TCA): 80% solution. Apply only to warts; powder/talc to remove unreacted acid. Repeat in office at weekly intervals; ideal for isolated lesions in pregnancy (3)[A].
- Recommendations for exophytic cervical warts: biopsy to exclude high-grade squamous intraepithelial lesion (SIL) (3)[A]
- Recommendations for vaginal warts: cryotherapy or TCA or bichloracetic acid (BCA) 80-90% (3)[A]
- Recommendations for urethral meatus warts: cryotherapy or podophyllin 10-25% in compound tincture of benzoin (3)[A]
- Recommendations for anal warts: cryotherapy, TCA or BCA 80-90%, or surgery; specialty consultation for intra-anal warts (3)[A]
Pregnancy Considerations
Cryotherapy, surgery, or TCA. Medications contraindicated in pregnancy: podophyllin, podophyllotoxin, sinecatechins, interferon, and imiquimod (3)[C]
Second Line
Intralesional interferon, photodynamic therapy, topical cidofovir (3)[A]
SURGERY/OTHER PROCEDURES
- Larger warts may require surgical excision, laser treatment, or electrocoagulation (including infrared therapy):
- Precaution: Laser treatment may create smoke plumes that contain HPV. CDC recommendation is for the use of a smoke evacuator no less than 2 inches from the surgical site. Masks are recommended; N95 the most efficacious (9)[A].
- 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.
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
No restrictions, except for sexual contact
Patient Monitoring
- Patients should be seen every 1 to 2 weeks until lesions resolve.
- Patients should follow up 3 months after completion of treatment.
- Persistent warts require biopsy.
- Sexual partners require monitoring.
PATIENT EDUCATION
- Provide information on HPV, STI prevention, and condom use.
- Explain to patients that it is difficult to know how or when a person acquired an HPV infection; a diagnosis in one partner does not prove sexual infidelity in the other partner.
- Emphasize the need for women to follow recommendations for regular Pap smears.
PROGNOSIS
- Asymptomatic infection persists indefinitely.
- Treatment has not clearly been shown to decrease transmissible infectivity.
- Warts may clear with treatment or resolve spontaneously. However, recurrences are frequent, particularly in the first 3 months, and may necessitate repeated treatments.
COMPLICATIONS
- Cervical dysplasia (probably does not occur with type 6 or 11, which cause most warts)
- Malignant change: Progression of condylomata to cancer rarely, if ever, occurs, although squamous cell carcinoma may coexist in larger warts.
- Urethral, vaginal, or anal obstruction from treatment
- The prevalence of high-grade dysplasia and cancer in anal canal is higher in HIV-positive than in HIV-negative patients, probably because of increased HPV activity.
REFERENCES
11 Gormley RH, Kovarik CL. Human papillomavirus-related genital disease in the immunocompromised host: part II. J Am Acad Dermatol. 2012;66(6):883.e1-883.e17; quiz 899-900.22 Unger ER, Fajman NN, Maloney EM, et al. Anogenital human papillomavirus in sexually abused and nonabused children: a multicenter study. Pediatrics. 2011;128(3):e658-e665.33 Workowski KA, Bolan GA; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1-137.44 Gerein V, Schmandt S, Babkina N, et al. Human papilloma virus (HPV)-associated gynecological alteration in mothers of children with recurrent respiratory papillomatosis during long-term observation. Cancer Detect Prev. 2007;31(4):276-281.55 Centers for Disease Control and Prevention. FDA licensure of bivalent human papillomavivaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2010;59(20):626-629.66 Centers for Disease Control and Prevention. Recommendations on the use of quadrivalent human papillomavirus vaccine in males-Advisory Committee on Immunization Practices (ACIP), 2011. MMWR Morb Mortal Wkly Rep. 2011;60(50):1705-1708.77 Stockfleth E, Beti H, Orasan R, et al. Topical Polyphenon E in the treatment of external genital and perianal warts: a randomized controlled trial. Br J Dermatol. 2008;158(6):1329-1338.88 Gotovtseva EP, Kapadia AS, Smolensky MH, et al. Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis. Sex Transm Dis. 2008;35(4):346-351.99 NIOSH Health Hazard Evaluation and Technical Assistance Reports, HETA 85-126-1932 (1988) and HETA 88-101-2008 (1990)
ADDITIONAL READING
- Bauer HM, Wright G, Chow J. Evidence of human papillomavirus vaccine effectiveness in reducing genital warts: an analysis of California public family planning administrative claims data, 2007-2010. Am J Public Health. 2012;102(5):833-835.
- Giuliano AR, Palefsky JM, Goldstone S, et al. Efficacy of quadrivalent HPV vaccine against HPV infection and disease in males. N Engl J Med. 2011;364(5):401-411.
- Gormley RH, Kovarik CL. Human papillomavirus-related genital disease in the immunocompromised host: part I. J Am Acad Dermatol. 2012;66(6):867.e1-867.e14; quiz 881-882.
CODES
ICD10
A63.0 Anogenital (venereal) warts
ICD9
078.11 Condyloma acuminatum
SNOMED
- 240542006 Anogenital warts (disorder)
- 237110007 Condyloma acuminata of vulva (disorder)
- 240598006 Penile warts (disorder)
CLINICAL PEARLS
- Condylomata acuminata are soft, skin-colored, fleshy lesions caused by HPV subtypes 6, 11, 16, 18, 31, 33, and 35.
- Quadrivalent HPV vaccine addresses the two most common HPV serotypes to be contracted in warts types 6 and 11 and the two most cancer-promoting types 16 and 18 (Gardasil).
- Vaccine: 0.5 mL IM first dose and at months 2 and 6
- The majority of sexually active men and women will have acquired a genital HPV infection, usually asymptomatic, at some time.
- No single therapy for genital warts is ideal for all patients or clearly superior to other therapies.
- Quadrivalent HPV vaccine is effective in preventing HPV infection, particularly if administered prior to the onset of engaging in sexual activity. Gardasil is approved and recommended for use in males and females aged 9 to 26 years.