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 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.

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:

• Cytodestructive therapy: aimed to destroy warty lesion
• Immunotherapy: acts by enhancing patient's immune system to clear infection (imiquimod, sinecatechins, interferons, HPV vaccine)
• No treatment is considered superior to the other. However, selection of the treatment may depend on the following factors:

• Wart size
• Number of warts
• Anatomic site of wart
• Wart morphology
• Patient preference
• Cost of treatment
• Convenience
• Adverse effects

Medical Therapy

• Human papillomavirus therapy

• Anogenital warts

• 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
• 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

• 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.

• 3.1 Urethral meatus warts

• Preferred regimen: Cryotherapy with liquid nitrogen

• 3.2 Vaginal warts

• Preferred regimen: Cryotherapy with liquid nitrogen 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

• 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.

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.