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.
Other articles worth reading