Human Papillomavirus (HPV) Infection

Human papillomavirus (HPV) causes warts. Some types cause skin warts, and other types cause raised or flat genital warts (lesions of the skin or mucous membranes of the genitals). Infection with certain HPV types can lead to cancer. Diagnosis of external warts is based on their clinical appearance. Multiple treatments exist, but few are highly effective unless applied repeatedly over weeks to months. Genital warts may resolve without treatment in immunocompetent patients but may persist and spread widely in patients with decreased cell-mediated immunity (eg, due to pregnancy or HIV infection). Vaccines are available to protect against many of the HPV strains that can cause genital warts and cancer.

(See also Overview of Sexually Transmitted Infections.)

 

HPV is the most common sexually transmitted infection (STI). HPV is so common that 80% of sexually active unvaccinated men and women get the virus at some point in their life ( 1). 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.

 

Etiology of HPV Infection

There are > 100 known types of HPV. Some cause common skin warts. Some infect primarily the skin and 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, anus, or penis

Anal, laryngeal, bladder, and oropharyngeal cancers

Bowenoid papulosis

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. Virtually all cervical cancer is caused by HPV; about 70% is caused by types 16 and 18, and many of the rest result from types 31, 33, 35, and 39. HPV types that affect mainly the anogenital area can be transmitted to the oropharynx by orogenital contact; type 16 appears responsible for many cases of oropharyngeal cancer. HPV types 16 and 18 can also cause cancer in other areas, including the vulva, vagina, and penis.

 

Pearls & Pitfalls

Virtually all cervical cancer is caused by HPV.

HPV is transmitted from lesions during skin-to-skin contact. The types that affect the anogenital region are usually transmitted sexually by penetrative 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.

 

Symptoms and Signs of HPV Infection

Warts 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 homosexual 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 flat endocervical or anal warts that are difficult to see and diagnose clinically.

 

 

 

Diagnosis of HPV Infection

Clinical evaluation, sometimes including colposcopy, anoscopy, or both

Genital warts are usually diagnosed clinically. Their appearance usually differentiates them from condyloma lata of secondary syphilis (which are flat-topped) and from carcinomas. However, serologic 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.

 

Endocervical and anal warts can be visualized only by colposcopy and anoscopy. Applying a 3 to 5% solution of acetic acid for a few minutes before colposcopy causes warts to whiten and enhances visualization and detection of small warts.

 

Clinicians should check for malignant oral lesions potentially caused by HPV during routine examination of the mouth and oral cavity.

 

Nucleic acid amplification tests (NAAT) for HPV DNA confirm the diagnosis and allow typing of HPV, but their role in HPV management is not yet clear.

 

Treatment of HPV Infection

Mechanical removal (eg, by cryotherapy, electrocauterization, laser, or surgical excision)

Topical treatment (eg, with antimitotics, caustics, 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] 2015 Sexually Transmitted Diseases Treatment Guidelines: Anogenital Warts).

 

Genital warts may be removed by

·         Cryotherapy

·         Electrocauterization

·         Laser

·         Surgical excision

·         Sometimes, topical treatments

A local or general anesthetic is used depending on the size and number to be removed. 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 newer 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.

 

For intraurethral lesions, thiotepa (an alkylating drug), instilled in the urethra, is effective. In men, 5-fluorouracil applied twice a day to three 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.

 

Endocervical lesions should not be treated until Papanicolaou (Pap) test results rule out other cervical abnormalities (eg, dysplasia, cancer) that may dictate additional treatment.

 

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

 

Sex partners of women with endocervical warts 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.

 

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

 

Prevention of HPV Infection

A 9-valent vaccine and a quadrivalent vaccine that protect against the 2 types of HPV (types 6 and 11) that cause > 90% of visible genital warts are available. 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 that protects against only types 16 and 18 is also available. The current recommendations from the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control are as follows:

 

For both males and females 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.

 

Key Points

·         Genital warts are caused by a few types of human papillomavirus (HPV).

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

·         Diagnose warts by inspection; HPV testing is available, but its role in HPV management is unclear.

·         Remove warts mechanically or using various topical treatments.

·         HPV vaccination is recommended for children and young adults of both sexes.

 

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