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Fruit of the Womb
Fruit of the Womb

Anogenital Warts (Condylomata acuminata) and Pregnancy

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I recently completed a seven-part series on cervical dysplasia and cancer in pregnancy. The incentive to begin that series came from a young patient who had a mildy abnormal Pap test and extensive involvement of her vagina, vulva, and perianal areas with anogenital warts (Condylomata acuminata). In my comments related to her care, I mentioned that we had discussed options for treatment of her warts. Subsequently, one of our readers contacted me and wanted to know specific details about my approach to the treatment of anogenital warts during pregnancy "because the problem seems to be getting worse rather than better." I used that query as an opportunity to complete a set of 'guidelines for managment of anogenital warts' that our residents could use in their clinics. It's rather long and rather 'clinical' but it also contains some useful information and a few 'pearls' so it is presented in its entirety below...

Background

  • Anogenital warts are caused by infection with human papillomaviruses (HPV) of which more than 120 different types have been identified
  • 80-90% anogenital warts are caused by HPV types 6 and 11 (nononcogenic types)
  • It is estimated 15 to 38% of sexually active adolescents have genital warts
  • Women are at increased risk for larger warts and more diffuse anogenital effectively prior to delivery, even if there is extensive involvement of the vagina, vulva, and perianal areas, unless the woman has an underlying involvement than men, but they are often more responsive to any form of therapy
  • Conditions under which there is down-regulation of the cell-mediated immune response, such as pregnancy, are associated with more severe disease
  • Many women will have spontaneous improvement in their condition within months following delivery
  • Genital warts are unsightly, uncomfortable, and psychologically traumatic, and they can be a nidus for superimposed bacterial infection (a source of risk for premature rupture of membranes and premature labor), increase the risk for neonatal HPV infection (anogenital, oral, and laryngeal), and complicate the repair of obstetrical lacerations
  • Anogenital warts found during pregnancy can often can be treated immunodeficiency condition or requires immunosuppressive therapy (e.g., HIV, SLE, pregestational diabetes, renal transplantation, tobacco abuse)

Therapeutic Options

  • Trichloroacetic acid (80%)
  • Imiquimod 5% cream
  • Cryotherapy
  • Surgical excision
  • Laser ablation
  • Podofilox 0.5%, podophyllin 25-50% in benzoin, and 5-fluorouracil are not recommended for use during pregnancy

Approaches to Therapy

  • Trichloroacetic acid (TCA) and/or Imiquimod 5% cream (Aldara 5%) are my preferred choices of topical therapy during pregnancy
  • TCA can be applied both externally and internally, but is extremely painful applied to any surface area external to the hymenal ring
  • Imiquimod cream should only be applied externally. Unpredictable, severe, painful, erosive reactions can occur when this drug is applied intravaginally . (Furthermore, because of the Th-1 augmenting effects of Imiquimod, the increased vascularity of the vagina during pregnancy, and the undocumented extent of systemic absorption under these circumstances, intravaginal application is not advised as it may pose an unrecognized risk to the baby, although I am not aware of any such complications actually occuring).

A recommended approach to therapy of both internal and external disease using these compounds is as follows:

Internal disease

  • Use a speculum for visualization
  • Cleanse the vagina with 5% acetic acid (be careful you do NOT use the TCA by mistake)
  • Dry the vagina
  • Apply TCA using a Q-tip to all visible intravaginal disease (trying to stay inside the hymenal ring), including visible cervical disease, starting at the apex of each wart and ending just around the base
  • Allow to dry before removing the speculum
  • Inform the patient she may feel a warm sensation.

External disease (minimal)

  • Isolated external lesions may be treated with TCA as well
  • First cleanse with 5% acetic acid, then dry
  • Apply TCA quickly to as many lesions as tolerated (you must work quickly because it will hurt)
  • Allow to dry thoroughly after application
  • CAUTION: Externally, TCA may cause scarring (internally it does not), particularly if reapplied to incompletely healed skin

External disease (extensive)

Imiquimod 5% cream can be used externally in conjunction with intravaginal TCA. The patient should be given a prescription for Imiquimod 5% cream and the following instructions:

  • At bedtime, wash, thoroughly rinse, and dry the vulvar and perianal areas that need to be treated (you may need to point out the warts to the patient in the clinic using a mirror)
  • Using a very small amount of the cream on a finger tip, rub the cream into each wart and just around the base until the cream vanishes
  • Suggest use of absorbent (cotton) underwear
  • Do not wash the areas until the next morning
  • Initially, prescribe three times per week application
  • If redness and irritation develops, discontinue therapy until it begins to resolve, then resume treatment (If the reaction is poorly tolerated, reduce to a twice weekly dosing schedule)
  • If the patient has no significant skin reaction within two weeks (and her warts have also not improved), increase the application frequency to daily until a reaction develops
  • Inform the patient at the outset that even if she develops a severe reaction, she will heal completely and without scarring
  • Imiquimod can be used for up to 16 weeks if necessary

Adjuncts to Therapy

  • If extensive intravaginal disease is treated, place the patient on metronidazole 500mg BID 7-14 days
  • Advise to discontinue smoking
  • Advise to refrain from intercourse during treatment
  • Suggest partner evaluation and treatment
  • Identify and control underlying medical conditions
  • Minimize doses of concurrent immunosuppressive therapy if possible

Follow-up

  • Schedule return visit in no less than 2-3 weeks; resolution of disease, regardless of therapeutic approach, depends on the inducement of a sufficient immune response and this can take time
  • Repeat evaluation and treatment as detailed above
  • Continue treatment up to 37 weeks
  • If the patient has no response to therapy, local excision or laser ablation can be offered, but this is not recommended beyond 34 weeks. (Combinations of Imiquimod and ablative therapy of external disease are safe and can be effective in recalcitrant cases

Management of Delivery

  • There is no indication for cesarean delivery if there is minimal disease
  • Indeed, even extensive disease presents only a relative contraindication to vaginal delivery
  • Cesarean can be discussed with the patient as an option, although this may not prevent the baby from acquiring HPV
  • If a baby is delivered through a birth canal with condylomata, try to avoid vigorous oropharyngeal suction to reduce the risk of inoculation of the respiratory tree

Genital Warts and Recurrent Respiratory Papillomatosis (RRP)

  • 7 of every 1000 children born to mothers with vaginal condylomata develop RRP, also referred to as ‘juvenile laryngeal papillomatosis (JLP) or ‘juvenile-onset recurrent respiratory papillomatosis (JORRP)
  • The risk is 231-fold higher than that of births in women without a history of genital warts
    RRP is the most common benign neoplastic disease of the larynx in children and adolescents
  • The mean age of onset in children is 4 years, so it is easy for us not to recognize the association between RRP and maternal genital warts
  • Labor > 10 hours in women with genital warts is accompanied by a two-fold greater risk of RRP in their children than those laboring
  • Cesarean delivery does not appear to be protective against RRP
  • Birth by cesarean section may be associated with increased risk for more severe disease among those who develop RRP, but the reasons for this are unclear
  • RRP can be a source of lifetime morbidity and mortality for the child, and incurs enormous costs to the health care system, estimated to range from $60,000 to $470,000 or more per patient
  • Although spontaneous remission is possible, pulmonary spread and malignant transformation have been reported.

References

Reeves WC, Ruparelia SS, Swanson KI, et al. National registry for juvenile-onset recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg. 2003;129:976-82.

Silverberg MJ, Thorsen P, Lindeberg H, et al. Condyloma in pregnancy is strongly predictive of juvenile-onset recurrent respiratory papillomatosis. Obstet Gynecol. 2003;101:645-52.

Stamataki S, Nikolpoulos TP, Korres S, Felekis D, et al. Juvenile recurrent respiratory papillomatosis: still a mystery disease with difficult management. Head Neck 2007;29:155-62.

Wiatrak BJ, Overview of recurrent respiratory papillomatosis. Curr Opin Otolaryngol Head Neck Surg. 2003;11:433-41.

Wiatrak BJ, Wiatrak DW, Broker TR, Lewis L. Recurrent respiratory papillomatosis: a longitudinal study comparing severity associated with human papilloma viral types 6 and 11 and other risk factors in a large pediatric population. Laryngoscope. 2004;114:1-23.

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