Genital Warts

What are Genital Warts

Genital warts are small growths in the genital area or anal area. They are caused by a type of germ (HPV virus).

This germ is spread from person to person during sex. It can be spread through vaginal, anal, and oral sex. Genital warts can lead to other problems if they are not treated.

Follow these instructions at home:

Medicines

• Apply over-the-counter and prescription medicines only as told by your doctor.
• Do notuse medicines that are meant for treating hand warts.
• Talk with your doctor about using anti-itch creams.

General instructions

• Do nottouch or scratch the warts.
• Do nothave sex until your treatment is done.
• Tell your current and past sexual partners about your condition. They may need treatment.
• Keep all follow-up visits as told by your doctor. This is important.
• After treatment, use condoms during sex.

Other Instructions for Women

• Women who have genital warts may need to be checked more often for cervical cancer.
• If you become pregnant, tell your doctor that you have had genital warts. The germ can be passed to the baby.

Contact a doctor if:

• You have redness, swelling, or pain in the area of the treated skin.
• You have a fever.
• You feel generally sick.
• You feel lumps in and around your genital area or anal area.
• You have bleeding in your genital area or anal area.
• You have pain during sex.

Detailed Info of Genital Warts 

6 Interesting Facts of Genital Warts

1. Genital warts are benign growths on anogenital skin or mucosa caused by sexually transmitted HPV, primarily serotypes 6 and 11
2. Usually no abnormal discoloration, but vary in size and appearance; size ranges from pinhead to large plaque, and appearance may be flat-topped, dome-shaped, or cauliflowerlike
3. Diagnosis is made by visual identification of lesions found in or around the genital area or anus; definitive diagnosis based on biopsy is not usually required
4. Treatment depends on size and number of warts, anatomic site, cost, adverse effects, and patient and physician preference
   • Options include patient-applied treatments (eg, podofilox, sinecatechins, imiquimod) and provider-administered treatments (eg, cryotherapy, trichloroacetic acid, bichloroacetic acid, surgical therapy)
5. No treatment is superior to any another; recurrences may occur after any form of therapy, and all treatments can result in local skin reactions
6. Untreated warts may resolve spontaneously, remain stable, or increase in size or number; spontaneous resolution occurs in up to one-third of patients within 1 year 

Pitfalls

• Failure to diagnose condyloma latum, a manifestation of secondary syphilis that has similar appearance, may delay adequate treatment and allow ongoing transmission of syphilis 

• Genital warts are benign growths on anogenital skin or mucosa caused by sexually transmitted HPV, primarily serotypes 6 and 11 
  • Also referred to as condylomata acuminata or venereal warts

Clinical Presentation

History

• Flat, papular, or pedunculated growths in or around the anogenital area
  • Vary in size from pinhead-sized to large cauliflowerlike masses
  • Commonly arise in areas of trauma, friction (during intercourse), or shaving 
• Typically no other symptoms occur
  • Depending on size and location, may present with pain, bleeding, or pruritus due to local irritation; large plaques may result in dyspareunia 
  • Rarely, large warts become macerated or infected 

Physical examination

• Warts are highly variable in size and appearance
  • May be flat-topped, dome-shaped, or cauliflowerlike 
  • Typically range in size from 1 to 5 mm in diameter, but may coalesce to form large plaques 
  • Warts usually match the skin tone but may be more heavily pigmented 
  • Never appear velvety or pearly 
• In males, warts may be found on the shaft of penis, glans, inner aspect of foreskin, urethral meatus, groin, pubis, scrotum, perineum, perianal area, and anal canal
• In females, warts may be found on the pubis, labia majora, labia minora, clitoris, introitus, urethral meatus, perineum, perianal area, anal canal, vagina, and ectocervix

Causes

• Infection with HPV
  • HPV-6 and HPV-11 (90% of patients)
    • Characterized as nononcogenic; primarily associated with genital warts and respiratory papillomatosis 
  • Other types (occasionally present, usually as coinfection with HPV-6 or HPV-11)
    • HPV-16
    • HPV-18
    • HPV-31
    • HPV-33
    • HPV-35
  • Sexually transmitted via oral, anal, or genital contact; transmission rates between sexual partners are high and transmission may occur in the absence of visible warts
    • Intrapartum transmission is also possible

Risk factors and/or associations

Age

• Highest prevalence in males: ages 25 to 29 years (estimated 5 cases per 1000 person-years) 
• Highest prevalence in females: ages 20 to 24 years (estimated 6.2 cases per 1000 person-years)

Sex

• More prevalent in females than in males

Other risk factors/associations

• Immunosuppressed state or HIV infection
• Multiple sexual partners
• Smoking 
• Unprotected sexual intercourse
• History of sexually transmitted infection
• Hormonal contraceptive use

Diagnostic Procedures

Primary diagnostic tools

• Diagnosis is made by visual inspection of external genital lesions; examination under magnification (eg, with colposcope) may be required
  • When examining males, include the urethral meatus and perianal area; digital rectal examination and proctoscopy can be offered when there is a suspicion for anal canal warts
  • When examining females, include the perianal area and a speculum examination for vaginal or cervical lesions; digital rectal examination and proctoscopy can be offered when there is a suspicion for anal canal warts
• Biopsy is necessary if lesions are atypical; biopsy may also be appropriate if lesions do not respond to standard therapy or worsen during therapy, particularly in immunocompromised patients (including those with HIV) 
• Offer screening tests to patients for other sexually transmitted infections
• HPV serotyping is not recommended, as it does not guide management
• Acetic acid application to detect subclinical lesions is not recommended

Procedures

• Small tissue sample is surgically removed for pathologic examination
• Lesions are atypical (eg, indurated, affixed to underlying tissue, bleeding, ulcerated) or diagnosis is uncertain
• Lesions do not respond to standard therapy or worsen during therapy, particularly in an immunocompromised (including HIV) patient
• Characteristic finding is the presence of koilocytes (mature squamous cells with clear perinuclear zone) 

Differential Diagnosis

Most common

• Condyloma latum
  • Manifestation of secondary syphilis (caused by Treponema palladium) 
  • Wartlike white-gray papules or plaques on intertriginous areas (eg, groin, labia, buttocks); may resemble flat genital warts 
    • Surface may erode and ooze 
  • Associated systemic symptoms and signs include lymphadenopathy, fever, generalized maculopapular or papulosquamous rash, alopecia, and leukoplakic or erythematous lesions on mucous membranes
  • Diagnosis is confirmed by demonstration of Treponema palladium spirochetes on darkfield examination, or fluorescent microscopy of lesion exudate or biopsy tissue and positive serologic test results
  • Failure to diagnose may delay adequate treatment and allow ongoing transmission of syphilis 
• Vulval, cervical, anal, or penile neoplasia
  • Premalignant or invasive lesions may appear similar to or coexist within anogenital warts
  • Suspect on basis of atypical clinical manifestations (eg, bleeding, ulceration, induration, pigmentation, palpable fixture to underlying tissue)
    • Maintain higher index of suspicion in immunocompromised patients, including patients with HIV
    • Also consider if lesions worsen or fail to respond to standard therapy for anogenital warts
  • Diagnose on basis of biopsy findings
• Bowenoid papulosis
  • Associated with oncogenic HPV infection 
  • Papules are composed of focal epidermal hyperplasia and dysplasia and are thought to represent an intermediate state between a genital wart and Bowen disease, analogous to squamous cell carcinoma in situ
  • Single or multiple red-brown flat-topped papules on the genitalia 
  • Papules are painless and nonpruritic
  • Definitive diagnosis requires biopsy
• Buschke-Löwenstein tumor (ie, giant condyloma)
  • Rare form of verrucous carcinoma associated with HPV-6 and HPV-11
  • Lesion slowly grows to form cauliflowerlike mass up to 15 cm in diameter
  • Associated with aggressive local infiltration into dermis and possible ulceration
  • Diagnose on basis of biopsy findings
• Molluscum contagiosum 
  • Common cutaneous viral infection caused by Molluscum contagiosum virus
  • Characterized by small, pearly, gray or flesh-colored papules with central umbilication
  • Lesions are usually asymptomatic
  • Diagnose on basis of characteristic clinical appearance; microscopic examination of stained central core of lesion may demonstrate Molluscum contagiosum virus or inclusion bodies
• Pearly penile papules
  • Normal anatomic variant of the glans; appearing as multiple 1-mm white papules arranged circumferentially around the corona or sulcus
  • Not associated with any other symptoms
  • Diagnose on basis of characteristic appearance
• Vestibular papillomatosis 
  • Normal anatomic variant of the vulva, akin to pearly penile papules in men
  • Not associated with any other symptoms
  • Diagnose on basis of characteristic appearance
• Fordyce granules
  • Visible sebaceous glands
  • Smooth 1- to 2-mm flesh-colored papules appearing on scrotum or labia
  • Not associated with any other symptoms
  • Diagnose on basis of characteristic appearance

Treatment Goals

• Elimination of warts and any associated symptoms or cosmetic concerns
  • Treatment may reduce, but likely does not eliminate, HPV; it is unknown whether treatment reduces future transmission 

Disposition

Recommendations for specialist referral

• Refer women with cervical warts to a gynecologist for evaluation and treatment 
• Refer patients with intra-anal or intrameatal warts for surgical management 
• Patients with bulky or extensive warts may require referral for surgical treatment

Treatment Options

Urgent biopsy or specialist referral is required if anogenital warts have atypical features (eg, bleeding, ulceration, pigmentation, palpable dermal infiltration), which suggest neoplastic change

Treatment depends on wart characteristics, anatomic site, cost, adverse effects, and patient and physician preference

• No definitive evidence supporting 1 treatment over another; recurrences may occur after all forms of therapy and all treatments can result in local skin reaction
  • For less extensive and smaller condylomata acuminata, topical treatment is usually recommended first 
  • Often a combination of treatment modalities is used 
  • Bulky, large clusters or extensive warts may require surgical removal
• Warts may resolve spontaneously within 1 year; it is acceptable for patients to forgo treatment and await spontaneous resolution
• In female patients, manage cervical warts in consultation with a gynecologist; biopsy exclusion of high-grade squamous intraepithelial neoplasia is required before treatment 
  • Exclude pregnancy before initiating treatment, as some modalities are contraindicated in pregnancy
• In patients with intra-anal and intrameatal warts, manage in consultation with a specialist
• The European Academy of Dermatology and Venereology Position Statement on anogenital warts (2019) suggests the following approach:
  • If more than 5 warts 
    • 2 months of immunotherapy (e.g., imiquimod, sinecatechins)
    • If warts still present, ablative therapy
    • A second 2-month treatment period of immunotherapy, for remaining warts and to prevent recurrence
    • If recurrence, ablative therapy and immunotherapy
  • If 1 to 5 warts 
    • Ablative therapy
    • Lesions heal
    • Immunotherapy (e.g., imiquimod, sinecatechins) for 2 months, for remaining warts and to prevent recurrence
    • If recurrence, ablative therapy and immunotherapy

Treatment may be applied by patient at home or administered by provider at clinic/office

• Patient-applied treatments of external warts include:
  • Podofilox solution or gel (clearance rates of 45%-94%)
  • Sinecatechins ointment (clearance rates of 40%-81%) 
  • Imiquimod cream (clearance rates of 35%-75%)
• Provider-administered agents or removal methods may be used to treat external and internal (vaginal, cervical, or intra-anal) warts, consisting of:
  • Cryotherapy with liquid nitrogen or cryoprobe (clearance rates of 46%-96%)
    • Use of cryoprobe in the vagina is not recommended owing to risk of perforation and fistula formation
    • A systematic review suggested that cryotherapy is an acceptable first line therapy to treat anogenital warts 
  • Application of trichloroacetic acid solution (clearance rates of 70%-100%) 
    • Not recommended for warts at urethral meatus
  • Various energy-based methods or surgical resection (eg, carbon dioxide laser, tangential scissor excision, shave excision, loop electrosurgical excision, electrocautery; followed by curettage)
    • Clearance rate depends on method but approaches 100% 
    • Surgical treatment may eliminate all warts in a single visit, but recurrence is possible
    • Requires appropriate training and office equipment

Drug therapy

• Podofilox 
  • Podofilox Topical gel; Infants†, Children† and Adolescents†: Using minimum amount to cover lesion, apply twice daily (morning and evening) with applicator for 3 days, then withhold use for 4 days. This 1-week cycle may be repeated 4 times or until there is no visible wart tissue. Max: 0.5 g/day. Limit treatment area to 10 cm2 or less of wart tissue.
  • Podofilox Topical gel; Adults: Using minimum amount to cover lesion, apply twice daily (morning and evening) with applicator for 3 days, then withhold use for 4 days. This 1-week cycle may be repeated 4 times or until there is no visible wart tissue. Max: 0.5 g/day. Limit treatment area to 10 cm2 or less of wart tissue.
• Sinecatechins 
  • Sinecatechins Topical ointment; Adults: Cover each wart with 0.5 cm strand ointment 3 times daily, leaving a thin layer on top. Use until warts gone or Max of 16 weeks. Retreatment has not been studied.
• Imiquimod (5% cream)
  • Imiquimod Topical cream; Infants† and Children 1 to 11 years†: In HIV-infected patients, guidelines recommend applying thin layer 3 time/week just before bedtime. Leave on for 6 to 10 hours, then wash off with soap and water. Continue until total clearance or Max: 16 weeks.
  • Imiquimod Topical cream; Adults, Adolescents, and Children >= 12 years: Apply thin layer 3 times/week just before bed. Leave on for 6 to 10 hours, then wash off with soap and water. Continue until total clearance or Max: 16 weeks.
• Trichloroacetic acid 
  • Trichloroacetic Acid Topical solution; Adults and adolescents: Apply a small amount directly to the wart 1- to 3-times per week. Affected area may be covered for 5 to 6 days. May reapply prn for 6 to 10 consecutive weeks. Use small amount to avoid spreading of liquid to adjacent skin areas. Protect surrounding skin with petroleum jelly. Patients should not sit or stand until the acid dries, at which time a white frosting will develop.

Nondrug and supportive care

Procedures

Cryotherapy 

General explanation

• Liquid nitrogen or a cryoprobe is applied to destroy warts by thermal cytolysis 

Indication

• External warts 
• Urethral meatus warts
• Cervical warts
• Intra-anal warts

Contraindications

• Use of a cryoprobe in the vagina is not recommended owing to the risk of vaginal perforation and fistula formation 

Interpretation of results

• Relatively high rate of recurrence (25%-40%), even after multiple treatments 

Surgical excision or energy-based methods of removal 

General explanation

• Abnormal tissue is removed under local anesthesia using 1 of the following methods: 
  • Carbon dioxide laser
  • Tangential scissor excision
  • Shave excision
  • Loop electrosurgical excision
  • Electrocautery
• Followed by curettage procedure or formal surgical excision
• Diode lasers have also been studied; further research is needed 

Indication

• Primary therapy for external warts
• Warts that are unresponsive or unsuitable for other treatments (eg, intraurethral, anal, or intra-anal warts)
• Bulky or extensive warts 

Special populations

• Patients in an immunosuppressed state or who are infected with HIV 
  • May develop larger or more numerous lesions
  • Management is same as for immunocompetent patient; however, patient may not respond as well to therapy or have more frequent recurrences after treatment 
• Pregnant women
  • Warts may enlarge and proliferate or become friable during pregnancy 
  • Presence of genital warts at delivery is associated with risk of respiratory papillomatosis in infant (rare) 
  • Avoid use of podofilox, imiquimod, and sinecatechins as data are insufficient
  • Management in consultation with an obstetrician is recommended

Complications

• Associated with treatment
  • Hypo- or hyperpigmentation or scarring may occur at site of treatment with some modalities 
  • Rarely, treatment can result in chronic pain syndromes (eg, vulvodynia, hyperesthesia of treatment site) or, in the case of intravaginal or intra-anal warts, scarring or fistula formation 
• Associated with disease
  • Neoplasia
    • Premalignant (eg, vulval, anal, or penile carcinoma in situ) or invasive lesions (eg, vulval, anal, or penile cancer) may arise within existing anogenital warts 

Prognosis

• Untreated warts may resolve spontaneously, remain stable, or increase in size or number 
  • Spontaneous resolution occurs in up to one-third of cases within 1 year Response rates vary with treatment modality and range from 45% to 94% 
  • Most anogenital warts respond to topical treatments within 3 months 
  • Surgical treatment may eliminate all warts in a single visit
• Recurrence is common, particularly within the first 3 months of treatment, with rates ranging from 25% to 67% 

Prevention

• HPV vaccination
  • Recommended to protect against cervical and other HPV-associated cancers in men and women; some vaccines also provide protection against HPV serotypes associated with genital warts
    • Bivalent HPV vaccine protects against HPV-16 and HPV-18, which are most commonly associated with cervical cancer (66% of cases); does not protect against types associated with genital warts 
    • Quadrivalent vaccine protects against HPV-6 and HPV-11 (commonly associated with genital warts), as well as HPV-16 and HPV-18 
      • Quadrivalent vaccine efficacy is reported to be as high as 90% for genital warts 
    • 9-valent vaccine protects against:
      • HPV-16
      • HPV-18
      • HPV-6
      • HPV-11
      • Plus 5 additional types that account for 15% of cervical cancers:
        • HPV-31
        • HPV-33
        • HPV-45
        • HPV-52
        • HPV-58
  • The Advisory Committee on Immunization Practices recommends routine HPV vaccination at 11 or 12 years of age (can be given starting at age 9 years); catch-up HPV vaccination is recommended for all persons through age 26 years who are not adequately vaccinated 
    • Catch-up HPV vaccination is not recommended for all adults older than 26 years 
      • Shared clinical decision-making regarding HPV vaccination is recommended for some adults aged 27 through 45 years who are not adequately vaccinated 
      • HPV vaccines are not licensed for use in adults older than 45 years 
    • For persons initiating vaccination before age 15, the recommended immunization schedule is 2 doses of vaccine; second dose should be administered 6 to 12 months after the first dose 
    • For persons initiating vaccination on or after 15th birthday, the recommended immunization schedule is 3 doses of vaccine; second dose should be administered 1 to 2 months after the first dose, and third dose should be administered 6 months after the first dose 
• Consistent and correct use of male condoms is recommended; however, these do not provide complete protection 

References

1: Karnes JB et al: Management of external genital warts. Am Fam Physician. 90(5):312-8, 2014  Reference