Human papillomavirus medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maliha Shakil, M.D. [2] Aysha Aslam, M.B.B.S[3]

Overview

There is no definitve medical treatment of HPV infection. However, treatment is mainly aimed to treat warts or precancerous lesions. Two types of medical therapy which may be considered are cytodestructive therapy and immunotherapy. No treatment is considered superior to the other. However, selection of the treatment may depend on the wart size, number of warts, anatomic site of wart, wart morphology, patient preference, cost of treatment, convenience, adverse effects. Medical therapies for human papillomavirus infection include either imiquimod, sinecatechins, or podofilox.[1][2][3][4][5][6]

Medical Therapy

There is no definitve medical treatment of HPV infection. However, treatment is mainly aimed to treat warts or precancerous lesions. Two types of medical therapy may be considered:[1]

  • Cytodestructive therapy: aimed to destroy warty lesion
  • Immunotherapy: acts by enhancing patient's immune system to clear infection (imiquimod, sinecatechins, interferons, bacillus calmette-Guerin, HPV vaccine)[2][3][4][5][6]
  • No treatment is considered superior to the other. However, selection of the treatment may depend on the following factors:[1]
  • Wart size
  • Number of warts
  • Anatomic site of wart
  • Wart morphology
  • Patient preference
  • Cost of treatment
  • Convenience
  • Adverse effects

Medical Therapy

  • Human papillomavirus therapy[1]
  • 1.Preferred regimen for External Anogenital Warts(i.e., penis, groin, scrotum, vulva, perineum, external anus, and perianus)
  • 1.1 Patient-applied: Imiquimod 3.75% or 5% cream OR Podofilox 0.5% solution or gel OR Sinecatechins 15% ointment[8][9][10][5][11][12][13][14][15][16]
  • 1.2 Provider-administered: Cryotherapy with liquid nitrogen or cryoprobe OR Trichloroacetic acid (TCA) OR Bichloroacetic acid (BCA) 80%-90% solution
  • Note (1): Many persons with external anal warts also have intra-anal warts. Thus, persons with external anal warts might benefit from an inspection of the anal canal by digital examination, standard anoscopy, or high-resolution anoscopy.
  • Note (2): Might weaken condoms and vaginal diaphragms.
  • 2.Alternative regimens for external genital warts[1][9]
  • 2.1 Urethral meatus warts
  • Preferred regimen: Cryotherapy with liquid nitrogen[17]
  • 2.2 Vaginal warts
  • Preferred regimen: Cryotherapy with liquid nitrogen[17] OR TCA OR BCA 80%–90% solution
  • Note: The use of a cryoprobe in the vagina is not recommended because of the risk for vaginal perforation and fistula formation
  • 2.3 Cervical warts
  • Preferred regimen: Cryotherapy with liquid nitrogen OR TCA OR BCA 80%–90% solution
  • Note: Management of cervical warts should include consultation with a specialist.For women who have exophytic cervical warts, a biopsy evaluation to exclude high-grade SIL must be performed before treatment is initiated.
  • 2.4 Intra-anal warts
  • Preferred regimen: Cryotherapy with liquid nitrogen OR TCA OR BCA 80%–90% solution
  • Note: Management of intra-anal warts should include consultation with a specialist.
  • 3. Specific considerations[1]
  • 3.1 Management of sex partners
  • Persons should inform current partner(s) about having genital warts because the types of HPV that cause warts can be passed on to partners. Partners should receive counseling messages that partners might already have HPV despite no visible signs of warts, so HPV testing of sex partners of persons with genital warts is not recommended.
  • 3.2 Pregnancy
  • Podofilox (podophyllotoxin), Podophyllin, and Sinecatechins should not be used during pregnancy. Imiquimod appears to pose low risk but should be avoided until more data are available.
  • Cesarean delivery is indicated for women with anogenital warts if the pelvic outlet is obstructed or if vaginal delivery would result in excessive bleeding.
  • Pregnant women with anogenital warts should be counseled concerning the low risk for warts on the larynx of their infants or children (recurrent respiratory papillomatosis).
  • Trichloroacetic acid may be used during pregnancy as it has no known fetal side effects.
  • 3.3 HIV infection
  • Data do not support altered approaches to treatment for persons with HIV infection.
  • Squamous cell carcinomas arising in or resembling anogenital warts might occur more frequently among immunosuppressed persons, therefore requiring biopsy for confirmation of diagnosis for suspicious cases
  • 3.4 High-grade squamous intraepithelial lesions
  • Biopsy of an atypical wart might reveal HSIL or cancer of the anogenital tract. In this instance, referral to a specialist for treatment is recommended.

Refractory or recurrent disease

For recurrent and refractory cases, there is no specific treatment modality. However, combination of immunotherapy with cytoreduction may be used. In case of multiple recurrent events, diagnosis should be reconsidered and biopsy may be warranted. [18][19][20][21]

Follow-up

  • Most anogenital warts respond within 3 months of therapy.
  • Factors that might affect response to therapy include immunosuppression and treatment compliance.
  • In general, warts located on moist surfaces or in intertriginous areas respond best to topical treatment.
  • A new treatment modality should be selected when no substantial improvement is observed after a complete course of treatment or in the event of severe side effects; treatment response and therapy-associated side effects should be evaluated throughout the course of therapy.

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Workowski, Kimberly A.; Bolan, Gail A. (2015-06-05). "Sexually transmitted diseases treatment guidelines, 2015". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 64 (RR-03): 1–137. ISSN 1545-8601. PMID 26042815.
  2. 2.0 2.1 Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR (2008). "Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis". Sex Transm Dis. 35 (4): 346–51. doi:10.1097/OLQ.0b013e31815ea8d1. PMID 18360317.
  3. 3.0 3.1 Garland SM, Waddell R, Mindel A, Denham IM, McCloskey JC (2006). "An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women". Int J STD AIDS. 17 (7): 448–52. doi:10.1258/095646206777689161. PMID 16820073.
  4. 4.0 4.1 Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL; et al. (1998). "Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus". Arch Dermatol. 134 (1): 25–30. PMID 9449906.
  5. 5.0 5.1 5.2 "Veregen: a botanical for treatment of genital warts". Med Lett Drugs Ther. 50 (1280): 15–6. 2008. PMID 18292715.
  6. 6.0 6.1 Eron LJ, Judson F, Tucker S, Prawer S, Mills J, Murphy K; et al. (1986). "Interferon therapy for condylomata acuminata". N Engl J Med. 315 (17): 1059–64. doi:10.1056/NEJM198610233151704. PMID 3531860.
  7. Bonnez W, Elswick RK, Bailey-Farchione A, Hallahan D, Bell R, Isenberg R; et al. (1994). "Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts". Am J Med. 96 (5): 420–5. PMID 8192173.
  8. Brodell LA, Mercurio MG, Brodell RT (2007). "The diagnosis and treatment of human papillomavirus-mediated genital lesions". Cutis. 79 (4 Suppl): 5–10. PMID 17508490.
  9. 9.0 9.1 Beutner KR, Reitano MV, Richwald GA, Wiley DJ (1998). "External genital warts: report of the American Medical Association Consensus Conference. AMA Expert Panel on External Genital Warts". Clin Infect Dis. 27 (4): 796–806. PMID 9798036.
  10. Beutner KR, Spruance SL, Hougham AJ, Fox TL, Owens ML, Douglas JM (1998). "Treatment of genital warts with an immune-response modifier (imiquimod)". J Am Acad Dermatol. 38 (2 Pt 1): 230–9. PMID 9486679.
  11. Tatti S, Swinehart JM, Thielert C, Tawfik H, Mescheder A, Beutner KR (2008). "Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: a randomized controlled trial". Obstet Gynecol. 111 (6): 1371–9. doi:10.1097/AOG.0b013e3181719b60. PMID 18515521.
  12. Friedman-Kien AE, Eron LJ, Conant M, Growdon W, Badiak H, Bradstreet PW; et al. (1988). "Natural interferon alfa for treatment of condylomata acuminata". JAMA. 259 (4): 533–8. PMID 3336177.
  13. Dinsmore W, Jordan J, O'Mahony C, Harris JR, McMillan A, Radcliffe KW; et al. (1997). "Recombinant human interferon-beta in the treatment of condylomata acuminata". Int J STD AIDS. 8 (10): 622–8. PMID 9310221.
  14. Cook K, Brownell I (2008). "Treatments for genital warts". J Drugs Dermatol. 7 (8): 801–7. PMID 18720702.
  15. Böhle A, Büttner H, Jocham D (2001). "Primary treatment of condylomata acuminata with viable bacillus Calmette-Guerin". J Urol. 165 (3): 834–6. PMID 11176481.
  16. Metawea B, El-Nashar AR, Kamel I, Kassem W, Shamloul R (2005). "Application of viable bacille Calmette-Guérin topically as a potential therapeutic modality in condylomata acuminata: a placebo-controlled study". Urology. 65 (2): 247–50. doi:10.1016/j.urology.2004.09.025. PMID 15708031.
  17. 17.0 17.1 Ting PT, Dytoc MT (2004). "Therapy of external anogenital warts and molluscum contagiosum: a literature review". Dermatol Ther. 17 (1): 68–101. PMID 14756893.
  18. "Recurrent condylomata acuminata treated with recombinant interferon alpha-2a. A multicenter double-blind placebo-controlled clinical trial. Condylomata International Collaborative Study Group". Acta Derm Venereol. 73 (3): 223–6. 1993. PMID 8105627.
  19. Petersen CS, Bjerring P, Larsen J, Blaakaer J, Hagdrup H, From E; et al. (1991). "Systemic interferon alpha-2b increases the cure rate in laser treated patients with multiple persistent genital warts: a placebo-controlled study". Genitourin Med. 67 (2): 99–102. PMC 1194640. PMID 2032716.
  20. Fleshner PR, Freilich MI (1994). "Adjuvant interferon for anal condyloma. A prospective, randomized trial". Dis Colon Rectum. 37 (12): 1255–9. PMID 7995154.
  21. Armstrong DK, Maw RD, Dinsmore WW, Blaakaer J, Correa MA, Falk L; et al. (1996). "Combined therapy trial with interferon alpha-2a and ablative therapy in the treatment of anogenital warts". Genitourin Med. 72 (2): 103–7. PMC 1195617. PMID 8698355.

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