Advancements in Pharmacotherapy for Noncancerous Manifestations of HPV

Ramya Kollipara, Erfon Ekhlassi, Christopher Downing, Jacqueline Guidry, Michael Lee, Stephen K Tyring, Ramya Kollipara, Erfon Ekhlassi, Christopher Downing, Jacqueline Guidry, Michael Lee, Stephen K Tyring

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted disease. Via infection of the basal epithelial cells, HPV causes numerous malignancies and noncancerous cutaneous manifestations. Noncancerous cutaneous manifestations of HPV, including common, plantar, plane, and anogenital warts, are among the most common reasons for an office visit. Although there are various therapies available, they are notoriously difficult to treat. HPV treatments can be grouped into destructive (cantharidin, salicylic acid), virucidal (cidofovir, interferon-α), antimitotic (bleomycin, podophyllotoxin, 5-fluorouracil), immunotherapy (Candida antigen, contact allergen immunotherapy, imiquimod) or miscellaneous (trichloroacetic acid, polyphenon E). The mechanism of action, recent efficacy data, safety profile and recommended regimen for each of these treatment modalities is discussed.

Keywords: HPV; condyloma; pharmacotherapy; treatment; warts.

References

    1. Forman D., de Martel C., Lacey C.J., Soerjomataram I., Lortet-Tieulent J., Bruni L., Vignat J., Ferlay J., Bray F., Plummer M., et al. Global burden of Human Papillomavirus and related diseases. Vaccine. 2012;30 doi: 10.1016/j.vaccine.2012.07.055.
    1. Cardoso J.C., Calonje E. Cutaneous manifestations of human papillomaviruses: A review. Acta. Dermatoven. APA. 2011;20:145–154.
    1. Rivera A., Tyirng S.K. Therapy of cutaneous human Papillomavirus infections. Dermatol. Ther. 2004;17:4411–4418. doi: 10.1111/j.1396-0296.2004.04047.x.
    1. Massing A.M., Epstein W.L. Natural history of warts. A two-year study. Arch. Dermtol. 1963;87:306–310. doi: 10.1001/archderm.1963.01590150022004.
    1. Moed L., Shwayder T.A., Chang M.W. Cantharidin revisited: A blistering defense of an ancient medicine. Arch. Dermatol. 2001;137:1357–1360. doi: 10.1001/archderm.137.10.1357.
    1. Baumbach J.L., Sheth P.B. Topical and intralesional antiviral agents. In: Wolverton S., editor. Comprehensive Dermatologic Drug Therapy. Walter Burns Saunders Company; Philadelphia, PA, USA: 2001. pp. 524–536.
    1. DeBengoa Vallejo R.B., Iglesias M.E.L., Gomez-Martın B., Sánchez Gómez R., Sáez Crespo A. Application of cantharidin and podophyllotoxin for the treatment of plantar warts. J. Am. Podiatr. Med. Assoc. 2008;98:445–450.
    1. Boull C., Groth D. Update: Treatment of cutaneous viral warts in children. Pediatr. Dermatol. 2011;28:217–229. doi: 10.1111/j.1525-1470.2010.01378.x.
    1. Ramirez-Fort M.K., Au S.C., Javed S.A., Loo D.S. Management of cutaneous human papillomavirus infection: Pharmacotherapies. Curr. Probl. Dermatol. 2014;45:175–185.
    1. Kwok C.S., Gibbs S., Bennett C., Hollard R., Abbbot R. Topical treatments for cutaneous warts. Cochrane Database Syst. Rev. 2012;9 doi: 10.1002/14651858.CD001781.pub3.
    1. Lipke M.M. An Armamentarium of Wart Treatments. Clin. Med. Res. 2006;4:273–293. doi: 10.3121/cmr.4.4.273.
    1. De Clercq E. Clinical potential of the acylic nucleoside phophonates cidofovir, adefovir, and tenofovir in treatment of DNA virus and retrovirus infections. Clin. Microbiol. Rev. 2003;16:569–596. doi: 10.1128/CMR.16.4.569-596.2003.
    1. Stern P.L., van der Burg S.H., Hampson I.N. Therapy of human papillomavirus-related disease. Vaccine. 2012;30(Suppl. S5) doi: 10.1016/j.vaccine.2012.05.091.
    1. Espana L.P., Del Boz J., Morano T.F., Villafranca J.A., Martin M.T. Topical cidofovir for plantar warts. Dermatol. Ther. 2014;27:89–93. doi: 10.1111/dth.12061.
    1. Broganelli P., Chiaretta A., Fragnelli B., Bernengo M.G. Intralesional cidofovir for the treatment of multiple and recalcitrant cutaneous viral warts. Dermatol. Ther. 2012;25:468–471. doi: 10.1111/j.1529-8019.2012.01477.x.
    1. Espana L.P., Boz J.D., Morano T.F., Villafranca J.A., Troya M. Successful treatment of periungal warts with topical cidofovir. Dermatol. Ther. 2014;27:337–342. doi: 10.1111/dth.12161.
    1. Gromley R.H., Kovarik C.L. Human papillomavirus—Related genital disease in the immunocompromised host: Part II. J. Am. Acad. Dermatol. 2014 doi: 10.1016/j.jaad.2010.12.049.
    1. Tasca R.A., Clarke R.W. Recurrent respiratory papillomatosis. Arch. Dis. Child. 2006;91:689–691. doi: 10.1136/adc.2005.090514.
    1. Broekema F.I., Dikkers F.G. Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis. Eur. Arch. Otorhinolaryngol. 2008;265:871–879. doi: 10.1007/s00405-008-0658-0.
    1. Cha S., Johnston L., Natkunam Y., Brown J. Treatment of verruca vulgaris with topical cidofovir in an immunocompromised patient: A case report and review of the literature. Transplant Infect. Dis. 2005;7:158–161. doi: 10.1111/j.1399-3062.2005.00099.x.
    1. Mulhem E., Pinelis S. Treatment of nongenital cutaneous warts. Am. Fam. Physician. 2011;84:288–293.
    1. Aksakal A.A., Ozden M.G., Atahan C., Onder M. Successful treatment of verruca plantaris with a single injection of interferon-α2a. Clin. Exp. Dermatol. 2008;34:16–19. doi: 10.1111/j.1365-2230.2008.02924.x.
    1. Viera M.H., Amini S., Huo R., Konda S., Block S., Berman B. Herpes simplex virus and human papillomavirus genital infections: New and investigational therapeutic options. Int. J. Dermatol. 2010;49:733–749.
    1. Dall’Oglio F., D’Amico V., Nasca M.R., Micali G. Treatment of cutaneous warts: An evidence-based review. Am. J. Clin. Dermatol. 2012;13:73–96. doi: 10.2165/11594610-000000000-00000.
    1. Yang J., Pu Y.G., Zeng Z.M., Yu Z.J., Huang N., Deng Q.W. Interferon for the treatment of genital warts: A systematic review. BMC Infect. Dis. 2009;9 doi: 10.1186/1471-2334-9-156.
    1. Brockmeyer N.H., Poffhoff A., Bader A., Hochdorfer B., Schlottmann R., Rasokat H., Altmeyer P., Kreuter A. Treatment of condylomata acuminate with pegylated interferon alfa-2b in HIV-infected patients. Eur. J. Med. Res. 2006;11:27–32.
    1. Dorr R.T. Bleomycin pharmacology: Mechanism of action and resistance, and clincal pharmacokinetics. Semin. Oncol. 1992;19(Suppl. S5):3–8.
    1. Dhar S.B., Rashid M.M., Islam A., Bhuiyan M. Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy. Indian J. Dermatol. Venereol. Leprol. 2009;74:262–267. doi: 10.4103/0378-6323.48428.
    1. Shelley W.B., Shelley E.D. Intralesional bleomycin sulfate therapy for warts. A novel bifurcated needle puncture technique. Arch. Dermatol. 1991;127:234–236.
    1. Munn S.E., Higgens E., Marshall M., Clement M. A new method of intralesional bleomycin therapy in the treatment of recalcitrant warts. Br. J. Dermatol. 1996;135:969–971. doi: 10.1046/j.1365-2133.1996.d01-1104.x.
    1. Abess A., Keel D.M., Graham B.S. Flagellate hyperpigmentation following intralesional bleomycin treatment of verruca plantaris. Arch. Dermatol. 2003;139:337–339.
    1. Allen A.L., Fosko S.W. Lymphangitis as a complication of intralesional bleomycin therapy. J. Am. Acad. Dermatol. 1998;39:295–297. doi: 10.1016/S0190-9622(98)70097-0.
    1. Vanhooteghem O., Richert B. Raynaud phenomenon after treatment of verruca vulgaris of the sole with intralesional injection of bleomycin. Pediatr. Dermatol. 2001;18:249–251. doi: 10.1046/j.1525-1470.2001.018003249.x.
    1. Gonzalez U.F., Gil C.M.C., Aguilar Martinez A., Guerra Rodriguez P., Sánchez de Paz F., García-Pérez A. Cutaneous toxicity of intralesional bleomycin administration in the treatment of periungal warts. Arch. Dermatol. 1986;122:974–975. doi: 10.1001/archderm.1986.01660210022008.
    1. Saitoh T., Kuramochi K., Imai T., Takata K., Takehara M., Kobayashi S., Sakaguchi K., Sugawara F. Podophyllotoxin directly binds a hinge domain in E2 of HPV and inhibits an E2/E7 interaction in vitro. Bioorg. Med. Chem. 2008;16:5815–5825. doi: 10.1016/j.bmc.2008.03.053.
    1. Kamal A., Srinivasa Reddy T., Polepalli S., Shalini N., Reddy V.G., Subba Rao A.V., Jain N., Shankaraiah N. Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors. Bioorg. Med. Chem. 2014;22:5466–5475. doi: 10.1016/j.bmc.2014.07.031.
    1. Yan J., Chen S.L., Wan H.N., Wu T.X. Meta-analysis of 5% imiquimod and 0.5% podophyllotoxin in the treatment of condylomata acuminate. Dermatology. 2006;213:218–223. doi: 10.1159/000095039.
    1. Komericki P., Akkilic-Materna M., Strimitzer T., Aberer W. Efficacy and safety of imiquimod versus podophyllotoxin in the treatment of anogenital warts. Sex. Transm. Dis. 2011;38:216–218. doi: 10.1097/OLQ.0b013e3181f68ebb.
    1. Kirby P., Dunne A., King D.H., Corey L. Double-blind randomized clinical trial of self-administered podofilox solution versus vehicle in the treatment of genital warts. Am. J. Med. 1990;88:465–469. doi: 10.1016/0002-9343(90)90424-C.
    1. Scheinfeld N., Lehman D.S. An evidence-based review of medical and surgical treatments of genital warts. Dermatol. Online J. 2006;12:5.
    1. Edwards A., Atma-Ram A., Thin R.N. Podophyllotoxin 0.5% v podophyllin 20% to treat penile warts. Genitourin. Med. 1988;65:263–265.
    1. Salk R.S., Grogan K.A. Topical 5% 5-fluorouracil cream in the treatment of plantar warts: A prospective, randomized, and controlled clinical study. J. Drugs Dermatol. 2006;5:418–424.
    1. Longley D.B. 5-Fluorouracil: Mechanisms of action and clinical strategies. Nat. Rev. Cancer. 2003;3:330–338. doi: 10.1038/nrc1074.
    1. Batista C.S., Atallah A.N. 5-FU for genital warts in non-immunocompromised individuals. Cochrane Database Syst. Rev. 2010;4 doi: 10.1002/14651858.CD006562.pub2.
    1. Gladsjo J.A., Alió Sáenz A.B., Bergman J., Kricorian G., Cunningham B.B. 5% 5-Fluorouracil cream for treatment of verruca vulgaris in children. Pediatr. Dermatol. 2009;26:279–285. doi: 10.1111/j.1525-1470.2008.00800.x.
    1. Swinehart J.M., Skinner R.B., McCarty J.M., Miller B.H., Tyring S.K., Korey A., Orenberg E.K. Development of intralesional therapy with fluorouracil/adrenaline injectable gel for management of condylomata acuminate: Two phase II clinical studies. Genitourin. Med. 1997;73:481–487.
    1. De Anda M.C., Dominguez J.G. Melonychia induced by topical treatment of periungual warts with 5-fluorouracil. Dermatol. Online J. 2013;19:10.
    1. Majid I., Imran S. Immunotherapy with intralesional Candida albicans antigen in resistant or recurrent warts: A study. Indian J. Dermtol. 2013;58:360–365. doi: 10.4103/0019-5154.117301.
    1. Johnson S.M., Roberson P.K., Horn T.D. Intralesional injection of mumps or Candida skin test antigens: A novel immunotherapy for warts. Arch. Dermatol. 2001;137:451–455.
    1. Horn T.D., Johnson S.M., Helm R.M., Roberson P.K. Intralesional immunotherapy of warts with mumps, Candida, and Trichophyton. Skin test antigens: A single-blinded, randomized, and controlled trial. Arch. Dermatol. 2005;141:589–594.
    1. Wilmer E.N., Burkhart C.N. Goodbye warts, hello vitiligo: Candida antigen-induced depigmentation. Pediatr. Dermatol. 2013;30:214–215. doi: 10.1111/pde.12049.
    1. Perman M., Sterling J.B., Gaspari A. The painful purple digit: An alarming complication of Candida albicans antigen treatment of recalcitrant warts. Dermatitis. 2005;16:38–40.
    1. Tyring S.K., Arany I., Stanley M.A. A randomized, controlled, molecular study of condylomata acuminata clearance during treatment with Imiquimod. J. Infect. Dis. 1998;2:551–555. doi: 10.1086/517472.
    1. Arican O., Guneri F., Bilgic K., Karaoglu A. Topical Imiquimod 5% cream in external anogenital warts: A randomized, double-blind, placebo-controlled study. J. Dermatol. 2004;8:627–631. doi: 10.1111/j.1346-8138.2004.tb00568.x.
    1. Hengge U.R., Esser S., Schultewolter T., Behrendt C., Meyer T., Stockfleth E., Goos M. Self-administered topical 5% imiquimod for the treatment of common warts and molluscum contagiosum. Br. J. Dermatol. 2000;143:1026–1031. doi: 10.1046/j.1365-2133.2000.03777.x.
    1. Baker D.A., Ferris D.G., Martens M.G., Fife K.H., Tyring S.K., Edwards L., Nelson A., Ault K., Trofatter K.F., Liu T., et al. Imiquimod 3.75% cream applied daily to treat anogenital warts: Combined results from women in two randomized, placebo-controlled studies. Infect. Dis. Obstet. Gynecol. 2011;2011 doi: 10.1155/2011/806105.
    1. Smith W.A., Siegel D., Lyon V.B., Holland K.E. Psoriasiform eruption and oral ulcerations as adverse effects of topical 5% imiquimod treatment in children: A report of four cases. Pediatr. Dermatol. 2013;30 doi: 10.1111/j.1525-1470.2012.01780.x.
    1. Rosenblatt A., de Campos Guidi H.G. Local and systemic adverse effects of imiquimod therapy for external anogenital warts in men: Report of three cases. Int. J. STD AIDS. 2012;23:909–910. doi: 10.1258/ijsa.2012.012076.
    1. Khandpur S., Sharma V.K., Sumanth K. Topical immunomodulators in dermatology. J. Postgrad Med. 2004;50:131–139.
    1. Park H.J., Choi Y.W., Kim S.H., Shin M.S., Lee S.W., Oh M.K., Choi H.Y. Change in cytokines in patients with warts after contact immunotherapy with squaric acid dibutylester. Clin. Exp. Dermatol. 2013;38:775–781.
    1. Choi Y., Kim do H., Jin S.Y., Lee A.Y., Lee S.H. Topical immunotherapy with diphenylcyclopropenone is effective and preferred in the treatment of periungual warts. Ann. Dermatol. 2013;25:434–439. doi: 10.5021/ad.2013.25.4.434.
    1. Aghaei S. Treatment of disseminated facial warts through contact immunotherapy with diphenylcyclopropenone (DPCP) Dermatol. Online J. 2006;12:10.
    1. Lee A.N., Mallory S.B. Contact immunothereapy with squaric acid dibutylester for the treatment of recalcitrant warts. J. Am. Acad. Dermatol. 1999;41:595–599.
    1. Dall’Oglio F., Nasca M.R., D'Agata O., Micali G. Adult and paediatric contact immunotherapy with squaric acid dibutylester (SADBE) for recurrent, multiple resistant, mucocutaneous anogenital warts. Sex Transm. Infect. 2002;78:309–310. doi: 10.1136/sti.78.4.309-a.
    1. Sanders B.B., Smith K.W. Dintrochlorobenzene immunotherapy of human warts. Cutis. 1981;27:389–392.
    1. Dunne E.F., Friedman A., Datta S.D., Markowitz L.E., Workowski K.A. Updates on human papillomavirus and genital warts and counseling messages from the 2010 sexually transmitted diseases treatment guidelines. Clin. Infect. Dis. 2011;53(Suppl. S3):143–152. doi: 10.1093/cid/cir703.
    1. Munoz-Santos C., Pigem R., Alsina M. New treatments for human papillomavirus infection. Actas Dermosifiliogr. 2013;104:883–889. doi: 10.1016/j.ad.2013.03.003.
    1. Hoy S.M. Polyphenon E 10% ointment: In immunocompetent adults with external genital and perianal warts. Am. J. Clin. Dermatol. 2012;13:275–281. doi: 10.2165/11209370-000000000-00000.
    1. Karnes J.B., Usatine R.P. Management of external genital warts. Am. Fam. Physician. 2014;90:312–318.
    1. Yanofsky V.R. Genital Warts. J. Clin. Aesthet. Dermatol. 2012;5:25–36.
    1. Godley M.J., Bradbeer C.S., Gellan M., Thin R.N. Cryotherapy compared with trichloroacetic acid in treating genital warts. Genitourin. Med. 1987;63:390–392.
    1. Pezeshkpoor F., Banihashemi M., Yousefzadeh H., Sharghi M., Hoseinzadeh H. Comparative study of topical 80% trichloroacetic acid with 35% trichloroacetic acid in the treatment of the common wart. J. Drugs Dermatol. 2012;11:e66–e69.
    1. Kodner C.M., Nasraty S. Management of genital warts. Am. Fam. Physician. 2004;70:2335–2342.

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