warts%20-%20anogenital
WARTS - ANOGENITAL
Anogenital warts (condylomas) are caused by human papillomavirus (HPV) with >90% of the lesions caused by genotypes 6 & 11.
Patients who present with visible warts may also be infected with high-risk HPVs (eg types 16 & 18) which can cause subclinical lesions that are associated with intraepithelial neoplasia, cervical cancer and anogenital cancer.
Many HPV infections are subclinical, transient, and clear spontaneously within 12 months but may also remain latent and reactivate after several years.

Principles of Therapy

  • Primary goal of treatment is to eliminate warts that cause physiological or psychological symptoms
  • All treatments have significant failure and recurrence rates as treatment does not eradicate the virus itself
  • No definitive evidence suggests that any of the treatment options are better than the others
  • Warts found in intertriginous areas or moist surfaces respond best to topical therapy
  • Sex partner evaluation is of no proven benefit in preventing transmission/reinfection or complication since the majority of partners are already subclinically infected
    • Assessment of presence of warts and other sexually transmitted infections (STIs) may be beneficial both to the patient and the sexual partner
  • Treatment choice depends on:
    • Morphology, number and distribution of warts
    • Cost and convenience of treatment
    • Adverse effects
    • Available resources
    • Experience of the physician
    • Age of the patient
    • Condition of the patient, eg pregnant or immunocompromised
    • Patient preference
  • Absence of significant response within 4-6 weeks warrants consideration for an alternative diagnosis, change in treatment, or referral to a specialist

Pharmacotherapy

Symptomatic Therapy

Saltwater Bath

  • Helps soothe and heal the genital area during treatment
  • 2 handfuls of plain salt per bath or 2 tbsp in large bowl done at least twice daily

Anesthetic

  • Xylocaine gel (2% preparation)
    • Local anesthetic that may be applied on raw areas prior to micturition and defecation

Local Imidazole Preparation

  • May be used if there is concomitant thrush infection

Silver Sulfadiazine Cream (1% Preparation)

  • May be used for large raw areas after ablation

Patient-Applied

Imiquimod (Topical)

  • May be used for all external anogenital warts, keratinized or nonkeratinized
  • Suitable for women and some men with foreskin-associated warts
  • Particularly useful for carpet warts (eg female introitus and perianal area)
  • Topical immune response modifier that stimulates the production of interferons and cytokines which produces localized immune response at the site of application
  • Wart clearance is comparable with other chemical agents, though response is slow in onset
    • Recurrence rate is said to be low
  • Not recommended in pregnancy or for internal lesions
  • Response to treatment may be delayed for several weeks
  • If warts do not clear up in 4 weeks, continue treatment
  • Therapy may be continued up to 16 weeks with clinical assessment every 4 weeks

Podophyllotoxin (Topical)

  • Podophyllotoxin is the purified extract of Podophyllin
  • May be used for visible, external, nonkeratinized genital warts and in certain urethral meatus warts
  • Binds to cellular microtubules and inhibits mitotic division causing necrosis of condylomas
  • Clearance of warts seems to be better than Podophyllin
    • Soft nonkeratinized warts respond well to treatment
    • Erosions that occur as the warts necrotize are shallow and heal within a few days
  • Not recommended for use in extragenital lesions eg anal warts, wart areas >10 cm2, internal warts, or warts not visualized
  • Exercise caution whenever applying to lesions, total volume used should be <0.5 mL/day
  • Contraindicated in pregnancy, lactation and children

Sinecatechins (Topical) 

  • Applied on external wart for up to 16 weeks 
  • Have antioxidant and immune-enhancing actions though exact mechanism of action is unknown 
  • Should not be used in the anus or vagina or by immunocompromised, pregnant or active-herpes infected women 
  • Can weaken diaphragms and condoms and should be washed off prior to inserting a vaginal tampon or sexual contact

Physician-Applied

TCA (Topical)

  • May be used at most anatomical sites but is most suitable for small acuminate or papular warts
    • Tends to be less effective for keratinized or large lesions but effective for dry and moist warts
    • Not recommended for large-volume warts because ulceration into the dermis may occur
  • Caustic agent that results in cellular necrosis
  • Initial response may be 70-81% but relapse may be up to 36%
  • Multiple applications may be necessary but are not well tolerated
  • Extremely corrosive to the skin
    • Careful application and protection of the surrounding skin with petroleum jelly is recommended
    • Neutralizing agents (eg Na bicarbonate or soap) should always be available
  • An intense burning sensation may be experienced after application
  • Can be used in pregnant women

Non-Pharmacological Therapy

No Treatment

  • An option at any site because of the possibility of spontaneous resolution and the uncertainty with regards to the effect of treatment and future transmission

Physician-Applied

  • Keratinized warts tend to respond better to physical ablative methods

Cryotherapy

  • Suitable for external and internal warts, and both dry and moist warts
  • Damages the cell membranes and organelles by freezing affected cells
    • Human papillomavirus (HPV) is not destroyed but is released into the extracellular area which may produce an immunologic response
  • Studies show efficacy rates between 65-85%
    • Repeated applications are usually needed
  • Liquid nitrogen is applied to each wart until 2 mm of surrounding skin has turned white
    • A freeze-thaw-freeze technique is used, freezing the lesion for 10-30 seconds depending on its size
    • Perform at weekly intervals
    • Due to the risk of vaginal perforation and fistula formation, use of vaginal cryoprobe is not recommended
  • Use of local anesthetic may ease pain if multiple warts or a large area of warts are to be treated
  • 1st-line therapy for pregnant patients
  • If 50% resolution is not achieved after 4 weeks, treat with Imiquimod
  • Contraindicated in patients with cryoglobulinemia
  • Pain followed by necrosis and sometimes blistering is common

Laser Treatment

  • Carbon Dioxide (CO2) Lasers
    • Useful for large-volume/extensive anogenital warts and warts at difficult anatomical sites (eg intra-anal, urethral meatus)
    • Vaporization of warts
    • Treatment can be painful and may leave scars
    • Not considered 1st-line treatment because of cost
    • Adequate protection of healthcare workers should be observed as smoke plume may contain HPV DNA

Photodynamic Therapy

  • Used in sensitive mucosal tissue including venereal warts and intraepithelial neoplasia
  • Uses 5-aminolevulinic acid (ALA) to stimulate porphyrin accumulation in the tissue which then acts as a photosensitizing agent
  • Studies show that results are equal or better than other treatment modalities with less or no scarring
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