Human Papillomavirus (HPV) Organism-Specific Therapy 

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Treatment of human papillomavirus (HPV) infection is directed to the macroscopic (ie, genital warts) or pathologic (ie, precancerous) lesions caused by infection. ^{[1, 2]} Genital HPV infection can clear spontane­ously; therefore, specific antiviral therapy is not recom­mended. In the absence of lesions, treatment is not recommended for subclinical genital HPV infection.

Treatment also is not recommended for cervical intraepithelial neoplasia 1 (CIN1). For CIN2 or greater, refer to the American Society for Colposcopy and Cervical Pathology (ASSCP) ^[3] and American Congress of Obstetricians and Gynecologists (ACOG) guidelines for evaluation and management. ^{[1, 2, 4]}

Genital warts are commonly asymptomatic but, depending on the size and location, may be painful or pruritic. Primary treatment should be targeted at symptomatic relief and removal of warts. Therapy may be applied by the patient or by the provider. There is no evidence that any one treatment is superior to the others. A treatment response is usually seen within 3 months.

Patient-applied therapy is as follows:

Podofilox 0.5% solution applied with a cotton swab or podofilox gel applied with a finger to genital warts BID for 3 days, followed by 4 days of no therapy; repeated as needed for up to 4 cycles (total wart area treated should not exceed 10 cm², and total volume of podofilox should be limited to 0.5 mL/day) or

Imiquimod 5% cream applied at bedtime 3 times weekly for up to 16 weeks; the treatment area should be washed with soap and water 6-10 hours after the application or

Sinecatechins 15% ointment applied with a finger (0.5-cm strand of ointment to each wart) TID to ensure coverage with a thin layer of ointment until complete clearance of warts, but not for >16 weeks; the medication should not be washed off after use; sexual (genital, anal, or oral) contact should be avoided while the ointment is on the skin

Provider-administered therapy is as follows:

Cryotherapy with liquid nitrogen or cryoprobe every 1-2 weeks or

Podophyllin resin 10%-25% in a compound tincture of benzoin every 1-2 weeks as needed or

Trichloroacetic acid (TCA) or bichloracetic acid (BCA) 80%-90% every 1-2 weeks as needed or

Surgical removal by tangential scissor excision, tangential shave excision, curettage, or electrosurgery

Treatment for vaginal warts is as follows:

Cryotherapy with liquid nitrogen (the use of a cryoprobe in the vagina is not recommended because of the risk of vaginal perforation and fistula formation) or

TCA or BCA 80%-90% applied to warts, repeated weekly if necessary; a small amount should be applied only to warts and allowed to dry, at which time a white frosting develops; if an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid

Treatment for urethral meatus warts is as follows:

Cryotherapy with liquid nitrogen or

Podophyllin 10%-25% in compound tincture of benzoin, repeated weekly if necessary; the treatment area and adjacent normal skin must be dry before contact with podophyllin; the safety of podophyllin during pregnancy has not been established; data are limited on the use of podofilox and imiquimod for treatment of distal meatal warts

Treatment for vaginal warts is as follows:

Cryotherapy with liquid nitrogen or

TCA or BCA 80%-90% applied to warts, repeated weekly if necessary; a small amount should be applied only to warts and allowed to dry, at which time a white frosting develops; if an excess amount of acid is applied, the treated area should be powdered with talc, sodium bicarbonate, or liquid soap preparations to remove unreacted acid; or

Surgical removal

HPV vaccines have been demonstrated to protect against diseases and precancerous conditions cause by the HPV types contained in each vaccine in individuals who have not previously been infected with those particular HPV types.

Depending on the HPV type, vaccination offers protection against the HPV types that cause 70% of cervical cancers (ie, types 16 and 18). One HPV vaccine is available in the United States to decrease the risk of certain cancers and precancerous lesions in women and men. The nonavalent HPV vaccine covers types 6, 11, 16, 18, 31, 33, 45, 52, and 58. ^{[7, 8, 9, 10, 14]} Cervarix (2vHPV) and Gardasil (4vHPV) were discontinued in the United States in October 2016. The FDA-approved indications for Gardasil 9 (9vHPV) are listed below (see Table 1).

Table 1. HPV Vaccine (Open Table in a new window)

Cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58

Genital warts (condyloma acuminata) caused by HPV types 6 and 11

Prevention of the following precancerous or dysplastic lesions: cervical intraepithelial neoplasia grades 1 and 2/3, cervical adenocarcinoma in situ, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3, anal intraepithelial neoplasia grades 1, 2, and 3

Anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58

Genital warts (condyloma acuminata) caused by HPV types 6 and 11

Prevention of the following precancerous or dysplastic lesions: anal intraepithelial neoplasia grades 1, 2, and 3

A 3-dose series is standard administration for the vaccine. In children and young adolescents, a 2-dose regimen is approved for the nonavalent vaccine (see Table 2).

Table 2. HPV Vaccine Dose Schedules (Open Table in a new window)

2-dose series at age 0 and 6-12 months*

OR

3-dose series at age 0, 2, and 6 months

Counseling considerations for patients diagnosed with HPV infection

Within an ongoing sexual relationship, both partners are usually infected at the time when one of them is diagnosed with HPV infection, even though signs of infection might not be apparent.

A diagnosis of HPV in one sex partner is not indicative of sexual infidelity in the other.

Treatments are available for the conditions caused by HPV (eg, genital warts), but not for the virus itself.

HPV does not affect a woman’s fertility or ability to carry a pregnancy to term.

Correct and consistent male condom use might lower the chances of transmitting genital HPV, but such use is not fully protective, because HPV can infect areas that are not covered by a condom.

Sexually active persons can lower their chances of getting HPV by limiting their number of partners; however, HPV is common and often goes unrecognized, and persons with only one lifetime sex partner can have the infection.

Genital warts commonly recur after treatment, especially in the first 3 months.

Persons with genital warts should inform current sex partner(s) because the warts can be transmitted to other partners; they should refrain from sexual activity until the warts are gone or removed.

Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines, 2010. MMWR. 2010. 59(No. RR-12):69-73.

Gearhart P, Randall TC, Buckley RM Jr. Human papillomavirus. Medscape Reference. May 4, 2011. [Full Text].

Wright TC, Massad LS, Dunton CJ. 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol. 346-355. 197(4):2007.

ACOG Committee on Practice Bulletins–Gynecology. ACOG Practice Bulletin no. 109: Cervical cytology screening. Obstet Gynecol. Dec 2009. 114(6):1409-20.

Saslow D, Andrews KS, Manassaram-Baptiste D, Loomer L, Lam KE, Fisher-Borne M, et al. Human papillomavirus vaccination guideline update: American Cancer Society guideline endorsement. CA Cancer J Clin. 2016 Sep. 66 (5):375-85. [Medline]. [Full Text].

FDA licensure of bivalent human papillomavirus vaccine (HPV2, Cervarix) for use in females and updated HPV vaccination recommendations from the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. May 28 2010. 59(20):626-9.

Joura E, et al. Efficacy and immunogenicity of a novel 9-valent HPV L1 virus-like particle vaccine in 16- to 26-year-old women. Abstract (SS 8-4) presented at EUROGIN 2014 November 5, 2013.

VanDamme P, et al. Immunogenicity and safety of a novel 9-valent HPV L1 virus-like particle vaccine in boys and girls 9-15 years old; comparison to women 16-26 years old. Abstract (SS 8-5) presented at EUROGIN 2014 November 5, 2013.

Use of 9-Valent Human Papillomavirus (HPV) Vaccine: Updated HPV Vaccination Recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. March 27, 2015. 64(11):300-304. [Full Text].

Gardasil 9 (human papillomavirus 9-valent vaccine, recombinant) [package insert]. Whitehouse Station, NJ: Whitehouse Station, NJ. December, 2015. Available at [Full Text].

Blomberg M, Friis S, Munk C, Bautz A, Kjaer SK. Genital warts and risk of cancer: a Danish study of nearly 50 000 patients with genital warts. J Infect Dis. 2012 May 15. 205(10):1544-53. [Medline].

Snoeck R. Papillomavirus and treatment. Antiviral Res. 2006 Sep. 71(2-3):181-91. [Medline].

Underwood MR, Shewchuk LM, Hassell AM, Phelps WC. Searching for antiviral drugs for human papillomaviruses. Antivir Ther. 2000 Dec. 5(4):229-42. [Medline].

Markowitz LE, Dunne EF, Saraiya M, Chesson HW, Curtis CR, Gee J, et al. Human papillomavirus vaccination: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2014 Aug 29. 63 (RR-05):1-30. [Medline]. [Full Text].

Cervical, vulvar, vaginal, and anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58

Genital warts (condyloma acuminata) caused by HPV types 6 and 11

Prevention of the following precancerous or dysplastic lesions: cervical intraepithelial neoplasia grades 1 and 2/3, cervical adenocarcinoma in situ, vulvar intraepithelial neoplasia grades 2 and 3, vaginal intraepithelial neoplasia grades 2 and 3, anal intraepithelial neoplasia grades 1, 2, and 3

Anal cancer caused by HPV types 16, 18, 31, 33, 45, 52, and 58

Genital warts (condyloma acuminata) caused by HPV types 6 and 11

Prevention of the following precancerous or dysplastic lesions: anal intraepithelial neoplasia grades 1, 2, and 3

2-dose series at age 0 and 6-12 months*

OR

3-dose series at age 0, 2, and 6 months

Shadab Hussain Ahmed, MD, AAHIVS, FACP, FIDSA Professor of Clinical Medicine, The School of Medicine at Stony Brook University Medical Center; Adjunct Clinical Associate Professor, Department of Medicine, New York College of Osteopathic Medicine of New York Institute of Technology; Attending Physician, Department of Medicine, Division of Infectious Diseases, Director of HIV Prevention Services, Administrative HIV Designee, Nassau University Medical Center

Shadab Hussain Ahmed, MD, AAHIVS, FACP, FIDSA is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Thomas E Herchline, MD Professor of Medicine, Wright State University, Boonshoft School of Medicine; Medical Consultant, Public Health, Dayton and Montgomery County (Ohio) Tuberculosis Clinic

Thomas E Herchline, MD is a member of the following medical societies: Alpha Omega Alpha, Infectious Diseases Society of America, Infectious Diseases Society of Ohio

Disclosure: Nothing to disclose.

Kelley Struble, DO Fellow, Department of Infectious Diseases, University of Oklahoma College of Medicine

Kelley Struble, DO is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Human Papillomavirus (HPV) Organism-Specific Therapy 

Research & References of Human Papillomavirus (HPV) Organism-Specific Therapy |A&C Accounting And Tax Services
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