Human papillomavirus medical therapy: Difference between revisions

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{{Human papillomavirus}}
{{Human papillomavirus}}
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{{CMG}} {{AE}} {{Maliha}} {{AA}} {{Jose}}


== Medical Therapy ==
==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]].<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref><ref name="pmid18360317">{{cite journal| author=Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR| title=Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis. | journal=Sex Transm Dis | year= 2008 | volume= 35 | issue= 4 | pages= 346-51 | pmid=18360317 | doi=10.1097/OLQ.0b013e31815ea8d1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18360317  }} </ref><ref name="pmid16820073">{{cite journal| author=Garland SM, Waddell R, Mindel A, Denham IM, McCloskey JC| title=An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women. | journal=Int J STD AIDS | year= 2006 | volume= 17 | issue= 7 | pages= 448-52 | pmid=16820073 | doi=10.1258/095646206777689161 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16820073  }} </ref><ref name="pmid9449906">{{cite journal| author=Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL et al.| title=Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus. | journal=Arch Dermatol | year= 1998 | volume= 134 | issue= 1 | pages= 25-30 | pmid=9449906 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9449906  }} </ref><ref name="pmid18292715">{{cite journal| author=| title=Veregen: a botanical for treatment of genital warts. | journal=Med Lett Drugs Ther | year= 2008 | volume= 50 | issue= 1280 | pages= 15-6 | pmid=18292715 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18292715  }} </ref><ref name="pmid3531860">{{cite journal| author=Eron LJ, Judson F, Tucker S, Prawer S, Mills J, Murphy K et al.| title=Interferon therapy for condylomata acuminata. | journal=N Engl J Med | year= 1986 | volume= 315 | issue= 17 | pages= 1059-64 | pmid=3531860 | doi=10.1056/NEJM198610233151704 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3531860  }} </ref>


Many sufferers of HPV warts report success using organic Apple Cider Vinegar (acidity 5%).  A paper towel soaked in ACV is applied onto the infected areas, and can be secured with duct tapeThose reporting the best results leave the soaked paper towel on for hours, or even all night during sleepThe result is that the wart turns bright white in color, and after several treatments, begins to turn black and die, eventually peeling off.[http://www.hpvsupport.com/viewtopic.php?p=58497&sid=7c75336b2238d7e3c588bedf4ec7fdf7] Many users report success mixing the ACV with small amounts of garlic and Tea Tree Oil as well when preparing the solutionThe ACV can also be swallowed orally when mixed with waterBecause the ACV can irritate sensitive skin area, some users report alternating treatments with a paper towel soaked in castor oil, which moisturizes skin while assisting in the removal of HPV warts.  [http://www.hpvfaq.com/treatments.asp?treatmentid=1008]
==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:<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref>
*Cytodestructive therapy: aimed to destroy warty lesion
*Immunotherapy: acts by enhancing patient's immune system to clear infection (imiquimod, sinecatechins, interferons, HPV vaccine)<ref name="pmid18360317">{{cite journal| author=Gotovtseva EP, Kapadia AS, Smolensky MH, Lairson DR| title=Optimal frequency of imiquimod (aldara) 5% cream for the treatment of external genital warts in immunocompetent adults: a meta-analysis. | journal=Sex Transm Dis | year= 2008 | volume= 35 | issue= 4 | pages= 346-51 | pmid=18360317 | doi=10.1097/OLQ.0b013e31815ea8d1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18360317 }} </ref><ref name="pmid16820073">{{cite journal| author=Garland SM, Waddell R, Mindel A, Denham IM, McCloskey JC| title=An open-label phase II pilot study investigating the optimal duration of imiquimod 5% cream for the treatment of external genital warts in women. | journal=Int J STD AIDS | year= 2006 | volume= 17 | issue= 7 | pages= 448-52 | pmid=16820073 | doi=10.1258/095646206777689161 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16820073  }} </ref><ref name="pmid9449906">{{cite journal| author=Edwards L, Ferenczy A, Eron L, Baker D, Owens ML, Fox TL et al.| title=Self-administered topical 5% imiquimod cream for external anogenital warts. HPV Study Group. Human PapillomaVirus. | journal=Arch Dermatol | year= 1998 | volume= 134 | issue= 1 | pages= 25-30 | pmid=9449906 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9449906 }} </ref><ref name="pmid18292715">{{cite journal| author=| title=Veregen: a botanical for treatment of genital warts. | journal=Med Lett Drugs Ther | year= 2008 | volume= 50 | issue= 1280 | pages= 15-6 | pmid=18292715 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18292715  }} </ref><ref name="pmid3531860">{{cite journal| author=Eron LJ, Judson F, Tucker S, Prawer S, Mills J, Murphy K et al.| title=Interferon therapy for condylomata acuminata. | journal=N Engl J Med | year= 1986 | volume= 315 | issue= 17 | pages= 1059-64 | pmid=3531860 | doi=10.1056/NEJM198610233151704 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3531860 }} </ref>
*No treatment is considered superior to the other. However, selection of the treatment may depend on the following factors:<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref>
:*Wart size
:*Number of warts
:*Anatomic site of wart
:*Wart morphology
:*Patient preference
:*Cost of treatment
:*Convenience
:*Adverse effects
===Medical Therapy===
* '''Human papillomavirus therapy'''<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref>
:* ''' Anogenital warts'''<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref><ref name="pmid8192173">{{cite journal| author=Bonnez W, Elswick RK, Bailey-Farchione A, Hallahan D, Bell R, Isenberg R et al.| title=Efficacy and safety of 0.5% podofilox solution in the treatment and suppression of anogenital warts. | journal=Am J Med | year= 1994 | volume= 96 | issue= 5 | pages= 420-5 | pmid=8192173 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8192173  }} </ref>
::* 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<ref name="pmid17508490">{{cite journal| author=Brodell LA, Mercurio MG, Brodell RT| title=The diagnosis and treatment of human papillomavirus-mediated genital lesions. | journal=Cutis | year= 2007 | volume= 79 | issue= 4 Suppl | pages= 5-10 | pmid=17508490 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17508490 }} </ref><ref name="pmid9798036">{{cite journal| author=Beutner KR, Reitano MV, Richwald GA, Wiley DJ| title=External genital warts: report of the American Medical Association Consensus Conference. AMA Expert Panel on External Genital Warts. | journal=Clin Infect Dis | year= 1998 | volume= 27 | issue= 4 | pages= 796-806 | pmid=9798036 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9798036  }} </ref><ref name="pmid9486679">{{cite journal| author=Beutner KR, Spruance SL, Hougham AJ, Fox TL, Owens ML, Douglas JM| title=Treatment of genital warts with an immune-response modifier (imiquimod). | journal=J Am Acad Dermatol | year= 1998 | volume= 38 | issue= 2 Pt 1 | pages= 230-9 | pmid=9486679 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9486679  }} </ref><ref name="pmid18292715">{{cite journal| author=| title=Veregen: a botanical for treatment of genital warts. | journal=Med Lett Drugs Ther | year= 2008 | volume= 50 | issue= 1280 | pages= 15-6 | pmid=18292715 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18292715  }} </ref><ref name="pmid18515521">{{cite journal| author=Tatti S, Swinehart JM, Thielert C, Tawfik H, Mescheder A, Beutner KR| title=Sinecatechins, a defined green tea extract, in the treatment of external anogenital warts: a randomized controlled trial. | journal=Obstet Gynecol | year= 2008 | volume= 111 | issue= 6 | pages= 1371-9 | pmid=18515521 | doi=10.1097/AOG.0b013e3181719b60 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18515521  }} </ref><ref name="pmid3336177">{{cite journal| author=Friedman-Kien AE, Eron LJ, Conant M, Growdon W, Badiak H, Bradstreet PW et al.| title=Natural interferon alfa for treatment of condylomata acuminata. | journal=JAMA | year= 1988 | volume= 259 | issue= 4 | pages= 533-8 | pmid=3336177 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3336177  }} </ref><ref name="pmid9310221">{{cite journal| author=Dinsmore W, Jordan J, O'Mahony C, Harris JR, McMillan A, Radcliffe KW et al.| title=Recombinant human interferon-beta in the treatment of condylomata acuminata. | journal=Int J STD AIDS | year= 1997 | volume= 8 | issue= 10 | pages= 622-8 | pmid=9310221 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9310221  }} </ref><ref name="pmid18720702">{{cite journal| author=Cook K, Brownell I| title=Treatments for genital warts. | journal=J Drugs Dermatol | year= 2008 | volume= 7 | issue= 8 | pages= 801-7 | pmid=18720702 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18720702 }} </ref><ref name="pmid11176481">{{cite journal| author=Böhle A, Büttner H, Jocham D| title=Primary treatment of condylomata acuminata with viable bacillus Calmette-Guerin. | journal=J Urol | year= 2001 | volume= 165 | issue= 3 | pages= 834-6 | pmid=11176481 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11176481  }} </ref><ref name="pmid15708031">{{cite journal| author=Metawea B, El-Nashar AR, Kamel I, Kassem W, Shamloul R| title=Application of viable bacille Calmette-Guérin topically as a potential therapeutic modality in condylomata acuminata: a placebo-controlled study. | journal=Urology | year= 2005 | volume= 65 | issue= 2 | pages= 247-50 | pmid=15708031 | doi=10.1016/j.urology.2004.09.025 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15708031 }} </ref>
:::* 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'''<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref><ref name="pmid9798036">{{cite journal| author=Beutner KR, Reitano MV, Richwald GA, Wiley DJ| title=External genital warts: report of the American Medical Association Consensus Conference. AMA Expert Panel on External Genital Warts. | journal=Clin Infect Dis | year= 1998 | volume= 27 | issue= 4 | pages= 796-806 | pmid=9798036 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9798036  }} </ref>
:::* Alternative treatments include [[podophyllin]] resin, intralesional [[interferon]], [[photodynamic therapy]], and topical [[cidofovir]]. Shared decision-making regarding these treatments, weighting on the risks and benefits is highly advisable. [[Podophyllin]] 10-25% is no longer recommended as the alternatives are safer, as severe [[toxicity]] has been described while treating large lesions. Application should be limited to <0.5 mL of [[podophyllin]], and the area affected by the treatment should be smaller than 10 cm2 of warts per session to avoid [[toxicity]]. The area to which treatment is administered also should not contain any open lesions, wounds, or friable tissue and the preparation should be thoroughly washed off 1–4 hours after application.<ref name="pmid34292926">{{cite journal| author=Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I | display-authors=etal| title=Sexually Transmitted Infections Treatment Guidelines, 2021. | journal=MMWR Recomm Rep | year= 2021 | volume= 70 | issue= 4 | pages= 1-187 | pmid=34292926 | doi=10.15585/mmwr.rr7004a1 | pmc=8344968 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34292926  }} </ref>
::* 3.1 '''Urethral meatus warts'''
:::* Preferred regimen: Cryotherapy with liquid nitrogen<ref name="pmid14756893">{{cite journal| author=Ting PT, Dytoc MT| title=Therapy of external anogenital warts and molluscum contagiosum: a literature review. | journal=Dermatol Ther | year= 2004 | volume= 17 | issue= 1 | pages= 68-101 | pmid=14756893 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14756893 }} </ref>
::* 3.2 '''Vaginal warts'''
:::* Preferred regimen: Cryotherapy with liquid nitrogen<ref name="pmid14756893">{{cite journal| author=Ting PT, Dytoc MT| title=Therapy of external anogenital warts and molluscum contagiosum: a literature review. | journal=Dermatol Ther | year= 2004 | volume= 17 | issue= 1 | pages= 68-101 | pmid=14756893 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14756893  }} </ref>  {{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
::* 3.3 '''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.
::* 3.4 '''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.


''Therapies are addressed in main articles covering [[#HPV-induced diseases|the various HPV-related diseases]].''
::* 4. '''Specific considerations'''<ref name=CDC>{{Cite journal| issn = 1545-8601| volume = 64| issue = RR-03| pages = 1–137| last1 = Workowski| first1 = Kimberly A.| last2 = Bolan| first2 = Gail A.| title = Sexually transmitted diseases treatment guidelines, 2015| journal = MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control| date = 2015-06-05| pmid = 26042815}}</ref>
 
:::* 4.1 '''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.
 
:::* 4.2 '''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.
 
:::* 4.3 '''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
 
:::* 4.4 '''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. 
<ref name="pmid8105627">{{cite journal| author=| title=Recurrent condylomata acuminata treated with recombinant interferon alpha-2a. A multicenter double-blind placebo-controlled clinical trial. Condylomata International Collaborative Study Group. | journal=Acta Derm Venereol | year= 1993 | volume= 73 | issue= 3 | pages= 223-6 | pmid=8105627 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8105627  }} </ref><ref name="pmid2032716">{{cite journal| author=Petersen CS, Bjerring P, Larsen J, Blaakaer J, Hagdrup H, From E et al.| title=Systemic interferon alpha-2b increases the cure rate in laser treated patients with multiple persistent genital warts: a placebo-controlled study. | journal=Genitourin Med | year= 1991 | volume= 67 | issue= 2 | pages= 99-102 | pmid=2032716 | doi= | pmc=1194640 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2032716  }} </ref><ref name="pmid7995154">{{cite journal| author=Fleshner PR, Freilich MI| title=Adjuvant interferon for anal condyloma. A prospective, randomized trial. | journal=Dis Colon Rectum | year= 1994 | volume= 37 | issue= 12 | pages= 1255-9 | pmid=7995154 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7995154  }} </ref><ref name="pmid8698355">{{cite journal| author=Armstrong DK, Maw RD, Dinsmore WW, Blaakaer J, Correa MA, Falk L et al.| title=Combined therapy trial with interferon alpha-2a and ablative therapy in the treatment of anogenital warts. | journal=Genitourin Med | year= 1996 | volume= 72 | issue= 2 | pages= 103-7 | pmid=8698355 | doi= | pmc=1195617 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8698355  }} </ref>
 
===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.
 
===Inform Patients About HPV===
The CDC 2021 STD Guidelines recommend patients to be oriented regarding HPV:
*Anogenital HPV infection is common. It usually infects the anogenital area but can infect other areas, including the mouth and throat. The majority of sexually active persons get HPV at some time during their lifetime, although most never know it.
*Partners tend to share HPV, and it is not possible to determine which partner transmitted the original infection. Having HPV does not mean that a person or his or her partner is having sex outside the relationship.
*Persons who acquire HPV usually clear the infection spontaneously, meaning that HPV becomes undetectable with no associated health problems.
*If HPV infection persists, genital warts, precancers, and cancers of the cervix, anus, penis, vulva, vagina, head, or neck might develop.
*Discussion of tobacco use, and provision of cessation counseling, is important because of its contribution to the progression of precancer and cancer.
*The types of HPV that cause genital warts are different from the types that can cause cancer.
*Many types of HPV are sexually transmitted through anogenital contact, mainly during vaginal and anal sex. HPV also might be transmitted during oral sex and genital-to-genital contact without penetration. In rare cases, a pregnant woman can transmit HPV to an infant during delivery.
*Treatments are available for the conditions caused by HPV but not for the virus itself.
*Having HPV does not make it harder for a woman to get pregnant or carry a pregnancy to term. However, certain precancers or cancers that HPV can cause, and the surgical procedures needed to treat them, can affect a woman’s ability to get pregnant or carry a pregnancy to term.
*No HPV test can determine which HPV infection will become undetectable and which will persist or progress to disease. However, in certain circumstances, HPV tests can determine whether a woman is at increased risk for cervical cancer. These tests are not for detecting other HPV-related problems, nor are they useful for women aged <25 years or men of any age.<ref name="pmid34292926">{{cite journal| author=Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I | display-authors=etal| title=Sexually Transmitted Infections Treatment Guidelines, 2021. | journal=MMWR Recomm Rep | year= 2021 | volume= 70 | issue= 4 | pages= 1-187 | pmid=34292926 | doi=10.15585/mmwr.rr7004a1 | pmc=8344968 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=34292926  }} </ref>


==References==
==References==


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Latest revision as of 00:18, 21 September 2021

Sexually transmitted diseases Main Page

Human papillomavirus Microchapters

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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 Anwar, M.B.B.S[3] José Eduardo Riceto Loyola Junior, M.D.[4]

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, 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]
  • Alternative treatments include podophyllin resin, intralesional interferon, photodynamic therapy, and topical cidofovir. Shared decision-making regarding these treatments, weighting on the risks and benefits is highly advisable. Podophyllin 10-25% is no longer recommended as the alternatives are safer, as severe toxicity has been described while treating large lesions. Application should be limited to <0.5 mL of podophyllin, and the area affected by the treatment should be smaller than 10 cm2 of warts per session to avoid toxicity. The area to which treatment is administered also should not contain any open lesions, wounds, or friable tissue and the preparation should be thoroughly washed off 1–4 hours after application.[17]
  • 3.1 Urethral meatus warts
  • Preferred regimen: Cryotherapy with liquid nitrogen[18]
  • 3.2 Vaginal warts
  • Preferred regimen: Cryotherapy with liquid nitrogen[18] 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
  • 3.3 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.
  • 3.4 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.
  • 4. Specific considerations[1]
  • 4.1 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.
  • 4.2 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.
  • 4.3 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
  • 4.4 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. [19][20][21][22]

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.

Inform Patients About HPV

The CDC 2021 STD Guidelines recommend patients to be oriented regarding HPV:

  • Anogenital HPV infection is common. It usually infects the anogenital area but can infect other areas, including the mouth and throat. The majority of sexually active persons get HPV at some time during their lifetime, although most never know it.
  • Partners tend to share HPV, and it is not possible to determine which partner transmitted the original infection. Having HPV does not mean that a person or his or her partner is having sex outside the relationship.
  • Persons who acquire HPV usually clear the infection spontaneously, meaning that HPV becomes undetectable with no associated health problems.
  • If HPV infection persists, genital warts, precancers, and cancers of the cervix, anus, penis, vulva, vagina, head, or neck might develop.
  • Discussion of tobacco use, and provision of cessation counseling, is important because of its contribution to the progression of precancer and cancer.
  • The types of HPV that cause genital warts are different from the types that can cause cancer.
  • Many types of HPV are sexually transmitted through anogenital contact, mainly during vaginal and anal sex. HPV also might be transmitted during oral sex and genital-to-genital contact without penetration. In rare cases, a pregnant woman can transmit HPV to an infant during delivery.
  • Treatments are available for the conditions caused by HPV but not for the virus itself.
  • Having HPV does not make it harder for a woman to get pregnant or carry a pregnancy to term. However, certain precancers or cancers that HPV can cause, and the surgical procedures needed to treat them, can affect a woman’s ability to get pregnant or carry a pregnancy to term.
  • No HPV test can determine which HPV infection will become undetectable and which will persist or progress to disease. However, in certain circumstances, HPV tests can determine whether a woman is at increased risk for cervical cancer. These tests are not for detecting other HPV-related problems, nor are they useful for women aged <25 years or men of any age.[17]

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 Workowski KA, Bachmann LH, Chan PA, Johnston CM, Muzny CA, Park I; et al. (2021). "Sexually Transmitted Infections Treatment Guidelines, 2021". MMWR Recomm Rep. 70 (4): 1–187. doi:10.15585/mmwr.rr7004a1. PMC 8344968 Check |pmc= value (help). PMID 34292926 Check |pmid= value (help).
  18. 18.0 18.1 Ting PT, Dytoc MT (2004). "Therapy of external anogenital warts and molluscum contagiosum: a literature review". Dermatol Ther. 17 (1): 68–101. PMID 14756893.
  19. "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.
  20. 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.
  21. Fleshner PR, Freilich MI (1994). "Adjuvant interferon for anal condyloma. A prospective, randomized trial". Dis Colon Rectum. 37 (12): 1255–9. PMID 7995154.
  22. 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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