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Human Papillomavirus (HPV) Infection

(Genital Warts; Condylomata Acuminata; Venereal Warts; Anogenital Warts)

By

Sheldon R. Morris

, MD, MPH, University of California San Diego

Last review/revision Jan 2023
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Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts. Skin or anogenital warts are diagnosed based on clinical appearance and are usually treated with topical medications or cytodestructive treatments. Genital warts may persist and spread widely in patients with decreased cell-mediated immunity (eg, due to pregnancy or HIV infection). Some types that infect mucosal epithelium can lead to anogenital or oropharyngeal cancer. Pap tests and/or HPV testing is recommended to screen for cervical cancer and anal cancer in high-risk patients. Vaccines are available to protect against many of the HPV strains that can cause genital warts and cancer.

HPV is the most common sexually transmitted infection (STI). HPV is so common that 80% of sexually active unvaccinated people get the virus at some point in their life (1 General reference Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts... read more General reference ). In the US, about 14 million people become newly infected with HPV each year; before the HPV vaccine became available, each year roughly 340,000 to 360,000 patients sought care for genital warts caused by HPV.

Most HPV infections clear spontaneously within 1 to 2 years, but some persist.

General reference

Etiology of HPV Infection

There are > 100 known types of HPV. Some infect cutaneous epithelium and cause common skin warts Warts Warts are common, benign, epidermal lesions caused by human papillomavirus infection. They can appear anywhere on the body in a variety of morphologies. Diagnosis is by examination. Warts are... read more Warts . Some infect primarily the mucosa of the anogenital region, as well as the oropharyngeal and laryngeal areas.

Important manifestations of anogenital HPV include

  • Genital warts (condyloma acuminatum)

  • Intraepithelial neoplasia and carcinoma of the cervix, vulva, vagina, anus, or penis

  • Laryngeal and oropharyngeal cancers

  • Bowenoid papulosis

Some data suggest HPV plays a role in the pathogenesis of some bladder cancers.

Condylomata acuminata are benign anogenital warts most often caused by HPV types 6 and 11, as are laryngeal and oropharyngeal warts. Low- and high-grade intraepithelial neoplasia and carcinoma may be caused by HPV.

Pearls & Pitfalls

  • Virtually all cervical cancer is caused by human papillomavirus (HPV).

HPV is transmitted from lesions during contact with skin or mucosa. The types that affect the anogenital region are usually transmitted sexually by vaginal or anal intercourse, but digital, oral, and nonpenetrative genital contact may be involved.

Genital warts are more common among immunocompromised patients. Growth rates vary, but pregnancy, immunosuppression, or maceration of the skin may accelerate the growth and spread of warts.

Reference

  • 1. Serrano B, Alemany L, Tous S, et al: Potential impact of a nine-valent vaccine in human papillomavirus related cervical disease. Infect Agent Cancer 7(1):38, 2012. doi:10.1186/1750-9378-7-38

Symptoms and Signs of HPV Infection

Warts caused by HPV appear after an incubation period of 1 to 6 months.

Visible anogenital warts are usually soft, moist, minute pink or gray polyps (raised lesions) that

  • Enlarge

  • May become pedunculated

  • Have rough surfaces

  • May occur in clusters

The warts are usually asymptomatic, but some patients have itching, burning, or discomfort.

In men, warts occur most commonly under the foreskin, on the coronal sulcus, within the urethral meatus, and on the penile shaft. They may occur around the anus and in the rectum, especially in men who have sex with men.

In women, warts occur most commonly on the vulva, vaginal wall, cervix, and perineum; the urethra and anal region may be affected.

HPV types 16 and 18 usually cause endocervical or anal intraepithelial lesions that are difficult to see and diagnose clinically.

Images of Genital Warts

Diagnosis of HPV Infection

  • Physical examination

  • HPV testing

  • Cervical, and sometimes anal, cytology (Pap test)

  • Sometimes colposcopy, anoscopy, or both

Genital warts are usually diagnosed with gross visual inspection. Their appearance usually differentiates them from condyloma lata Secondary syphilis Secondary syphilis of secondary syphilis (which are flat-topped) and from carcinomas. However, serologic tests for syphilis Diagnostic tests for syphilis Syphilis is caused by the spirochete Treponema pallidum and is characterized by 3 sequential symptomatic stages separated by periods of asymptomatic latent infection. Common manifestations... read more Diagnostic tests for syphilis (STS) should be done initially and after 3 months. Biopsies of atypical, bleeding, ulcerated, or persistent warts may be necessary to exclude carcinoma.

Cervical and anal intraepithelial lesions can be visualized only by colposcopy and anoscopy. Applying a 3 to 5% solution of acetic acid for a few minutes before colposcopy causes lesions to whiten and enhances visualization and detection of small lesions. Screening for cervical cancer Diagnosis Cervical cancer is usually a squamous cell carcinoma; less often, it is an adenocarcinoma. The cause of most cervical cancers is human papillomavirus infection. Cervical neoplasia is often asymptomatic... read more Diagnosis is discussed elsewhere in THE MANUAL.

Nucleic acid amplification tests (NAATs) for oncogenic HPV subtypes are used as part of routine cervical cancer screening in women. Initial tests typical detect any one of at l3 common high-risk types. Follow-up HPV genotype tests may be done to detect the most high-risk types, typically 16, 18, or 45. No HPV testing for men is available for clinical use.

Diagnosis references

  • 1. World Health Organization (WHO): Human papillomavirus (‎HPV)‎ nucleic acid amplification tests (‎NAATs)‎ to screen for cervical pre-cancer lesions and prevent cervical cancer; policy brief; 16 March 2022

  • 2. International Agency for Research on Cancer: A practical manual on visual screening for cervical neoplasia; Anatomical and pathological basis of visual inspection with acetic acid (VIA) and with Lugol’s iodine (VILI). IARC Technical Publication No. 41, 2003. ISBN 92 832 2423 X

Treatment of HPV Infection

  • Cytodestructive therapy or excision (eg, by caustics, cryotherapy, electrocauterization, laser, or surgical excision)

  • Topical medications (eg, with antimitotics or interferon inducers)

No treatment of anogenital warts is completely satisfactory, and relapses are frequent and require retreatment. In immunocompetent patients, genital warts may resolve without treatment. In immunocompromised patients, warts may be less responsive to treatment.

Because no treatment is clearly more efficacious than others, treatment of anogenital warts should be guided by other considerations, mainly wart size, number, and anatomic site; patient preference; cost of treatment; convenience; adverse effects; and the practitioner's experience (see the Centers for Disease Control and Prevention [CDC] 2021 Sexually Transmitted Infections Treatment Guidelines: Anogenital Warts).

Genital warts may be treated with

  • Caustics

  • Topical medications

  • Cryotherapy

  • Electrocauterization

  • Laser

  • Surgical excision

A local or general anesthetic is used depending on the size and number to be removed. Extensive vulvovaginal warts may require laser ablation. For anal warts, removal with a resectoscope may be the most effective treatment; a general anesthetic is used.

Topical treatments include antimitotics (eg, podophyllotoxin, podophyllin, 5-fluorouracil), caustics (eg, trichloroacetic acid), interferon inducers (eg, imiquimod), and sinecatechins (a botanical product with an unknown mechanism). These are widely used but usually require multiple applications over weeks to months and are frequently ineffective. Before topical treatments are applied, surrounding tissue should be protected with petroleum jelly. Patients should be warned that after treatment, the area may be painful.

Interferon alfa (eg, interferon alfa-2b, interferon alfa-n3), intralesionally or IM, has cleared intractable lesions on the skin and genitals, but optimal administration and long-term effects are unclear. Also, in some patients with bowenoid papulosis of the genitals (caused by type 16 HPV), lesions initially disappeared after treatment with interferon alfa but reappeared as invasive cancers.

By removing the moist underside of the prepuce, circumcision may prevent recurrences in uncircumcised men.

Current sex partners of people with genital warts should be examined and, if infected, treated.

For intraurethral lesions, thiotepa (an alkylating medication), instilled in the urethra, is effective. In men, 5-fluorouracil applied 2 to 3 times a day is highly effective for urethral lesions, but rarely, it causes swelling, leading to urethral obstruction. Intraurethral lesions are typically managed by a urologist.

Vulvar and vaginal intraepithelial neoplasia are treated with surgical excision.

Sex partners of patients with cervical intraepithelial neoplasia or carcinoma and of patients with bowenoid papulosis should be counseled and screened regularly for HPV-related lesions. A similar approach can be used for HPV in the rectum.

Management of cancers caused by HPV is discussed elsewhere in THE MANUAL.

Prevention of HPV Infection

A 9-valent vaccine and a quadrivalent vaccine protect against the 2 types of HPV (types 6 and 11) that cause > 90% of visible genital warts. These vaccines also protect against the 2 types of HPV (types 16 and 18) that cause most cervical cancers. The 9-valent vaccine also protects against other types of HPV (types 31, 33, 45, 52, and 58) that cause about 15% of cervical cancers. A bivalent vaccine protects against only types 16 and 18.

Only the 9-valent vaccine is available in the US.

The current recommendations from the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control are as follows:

For both females and males up to age 26 years: HPV vaccine is recommended at age 11 or 12 years (can start at age 9 years) and for previously unvaccinated or not adequately vaccinated patients up through age 26 years.

For adults 27 to 45 years: Clinicians should engage in a shared decision-making discussion with patients to determine whether they should be vaccinated.

Because HPV can be transmitted by skin-to-skin contact, condoms do not fully protect against infection.

Key Points

  • Anogenital warts are caused by human papillomavirus (HPV), most commonly types 6 and 11.

  • HPV types 16 and 18 cause about 70% of cervical cancers and can cause cancer in other areas, including the vulva, vagina, penis, anus, and oropharynx.

  • Diagnose warts by inspection; HPV testing is available to screen for cervical cancer.

  • Treat warts with cytodestructive treatments, topical medications, or surgical excision.

  • Treat cervical, vaginal, vulvar, or anal intraepithelial neoplasia with ablation or excision or manage with close surveillance.

  • HPV vaccination is recommended for children and young adults.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

Drug Name Select Trade
Acetasol, Borofair, VoSoL
Adrucil, Carac, Efudex, Fluoroplex, Tolak
Tri-Chlor
Aldara, Zyclara
Veregen
Intron A, Intron A Multidose Pen
Alferon N
TEPADINA
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