Genital warts appear as characteristic well-circumscribed, exophytic
papules that may be pedunculated. Some warts may be flat. The adjacent
skin usually appears normal. They range in size from a few millimeters
to several centimeters, with some warts coalescing to form larger
plaques. The median number of warts in an individual patient is
seven although there is a large range from patient to patient.
Most genital warts in circumcised men occur in the penile shaft.
In uncircumcised men, they occur mainly in the preputial cavity
where the penile shaft meets the glans (see Figure 15–1). Other
common locations for genital warts in men include the perianal area
(see Figure 15–2), particularly among men who have sex
with men (MSM), and the urethral meatus. Less frequently, genital
warts are seen on the scrotum and perineum. Although not the focus
of this chapter, intra-anal warts can be very common as well. Among
women, most lesions are found in the posterior introitus, the labia
majora and minora (see Figure 15–3), and the clitoris.
Other less common locations in women are the perineum, vagina, anus,
cervix, and urethra.
Penile warts. Multiple soft papules on the glans penis
and the prepuce. (Reproduced, with permission, from Wolff K, Johnson
RA, Summond D. Fitzpatrick’s Color
Atlas and Synopsis of Clinical Dermatology, 5th ed. McGraw-Hill,
Large, circumferential perianal genital warts in an
HIV-infected patient. Multiple verrucous papules have coalesced
into a large plaque causing obstructive symptoms. (Courtesy of Tina
Clark, NP, University of California at San Francisco.)
Vulvar warts. Multiple soft papules on the labia. (Reproduced,
with permission, from Wolff K, Johnson RA, Summond D. Fitzpatrick’s
Color Atlas and Synopsis of Clinical Dermatology, 5th ed. McGraw-Hill,
Patients with genital warts may complain of itching, burning,
bleeding, and pain. Patients with large genital warts may have a
sensation of fullness and this may interfere with intercourse, vaginal
delivery, and defecation. However, many patients have no symptoms.
Laboratory Findings and Special Examinations
Most genital warts are diagnosed by the characteristic appearance
on clinical examination only. If lesions look atypical or have features
that may be consistent with malignancy such as induration, ulceration,
and pigmentation, biopsy with histologic evaluation should be considered.
Colposcopy with Acetic Acid
Colposcopy uses a powerful light source and binocular lenses to
enable providers to identify HPV-associated lesions. Typically colposcopy
is used in conjunction with acetic acid to aid in the visualization
of affected tissue. Following the application of 3–5% acetic
acid for 3–5 minutes, an acetowhite area signifies HPV
infected tissue in contrast to normal surrounding tissue. Although originally
designed to evaluate the female genital tract, the application of
colposcopy has expanded to evaluate other anatomic sites such as
the penis and the anus. Cervical colposcopy and high-resolution
anoscopy (“colposcopy” of the anal canal) are
typically performed after an abnormal cytologic test on cervical
and anal cancer screening, respectively. However, this method is occasionally
used for the evaluation of genital warts as well.
The Pap test is the cornerstone of cervical cancer and CIN screening
and has been very successful in lowering cervical cancer incidence
and mortality where it has been implemented. There is no role for
the use of cytologic tests to diagnose genital warts, but women
presenting with genital warts should be screened with Pap tests.
The CDC recommends that providers perform a cervical Pap test at
the time of a pelvic examination for STD screening in women who
have not had a Pap test within the preceding 12–36 months.
This is because women attending STD clinics have a five times higher
prevalence of CIN than women attending family planning clinics,
and a history of STDs is a risk factor for invasive cervical cancer.
Cervical cancer screening guidelines have been issued by the American
Cancer Society, the US Preventative Services Task Force, and the
American College of Obstetricians and Gynecologists.
Cervical cytologic findings are classified as abnormal or normal.
The abnormal category includes high-grade squamous intraepithelial
lesions (HSIL), low-grade squamous intraepithelial lesions (LSIL),
atypical squamous cells that may be of undetermined significance
(ASC-US), or those that are suspicious for HSIL (ASC-H). (For further
discussion of abnormal cervical findings, see Chapter 29.)
Similar to the association between genital warts and CIN, there
is a risk of anal intraepithelial neoplasia in men and women with
anogenital warts. We believe that certain groups, such as MSM, HIV-infected
women and men regardless of sexual orientation, women with a history
of vulvar or cervical cancer, and transplant recipients, are at
the highest risk of anal intraepithelial neoplasia and anal cancer
and should be screened with anal cytology. Anal cytologic testing
every 1–2 years has been projected to be a cost-effective
intervention to prevent anal cancer in HIV-infected MSM, with cytologic
testing every 2–3 years for HIV-uninfected MSM. To perform
anal cytologic testing, we insert a water-moistened Dacron swab
in the anal canal, then withdraw the swab slowly while maintaining
some pressure against the anal canal. In this way, we obtain exfoliated
cells from the lower rectum, squamocolumnar junction, and anal canal.
Similar to the system used in cervical cancer and CIN screening,
anal cytologic findings are classified as normal, ASC-US, ASC-H,
LSIL, and HSIL. Individuals with abnormal findings (ASC-US, ASC-H,
LSIL, and HSIL) are referred for high-resolution anoscopy, in which
equipment identical to that used in cervical colposcopy is employed
to aid in the identification of lesions that have contributed to abnormal
Histologic examination of genital warts reveals HPV-induced abnormalities
in the epidermis, including acanthosis (thickening of the stratum
spinosum), parakeratosis (retention of nuclei in the cells of the
stratum corneum), and hyperkeratosis (thickening of the stratum
corneum), leading to a typical papillomatosis formation. Other characteristic
findings on tissue examination of a biopsy specimen are koilocytes
(squamous epithelial cells with an abnormal nucleus within a large
cytoplasmic halo). Biopsies are not necessary for the diagnosis
of genital warts, given their unique clinical appearance. However,
we recommend obtaining a biopsy specimen if there are atypical findings
such as pigmentation, ulceration, or firm, nodular masses, to rule
out high-grade dysplasia or malignant disease.
Techniques using polymerase chain reaction (PCR) and hybrid capture
technology are sensitive and specific methods of diagnosing HPV
infection. PCR technology uses the action of DNA polymerase on specific
primers to amplify target HPV DNA. HPV type-specific PCR assays
are available. Hybrid capture employs RNA probes specific for the
identification of certain grouped oncogenic (high-risk) or nononcogenic
(low-risk) HPV types, but does not give individual type-specific
information. PCR and hybrid capture methods can be used to diagnose
HPV infection using both exfoliated cells and tissue specimens obtained
by biopsy. Although PCR and hybrid capture are commonly used in
research settings, only hybrid capture is cleared by the FDA as
an adjunct to cervical cytologic screening to detect CIN. PCR and
hybrid capture are not routinely used for the diagnosis or management
of genital warts.
Enzyme-linked immunoabsorbent assay (ELISA) technology is used to
provide IgM and IgG serologic measures of HPV infection by targeting
type-specific viruslike particles. Patients with genital warts and
other HPV-associated diseases have been found to have type-specific
HPV serologic responses to HPV-6 and HPV-11. The significance of
HPV serologic measures is unclear, and these measures are currently
used only in research settings. Antibody responses to HPV may persist
for several years or resolve with the resolution of disease, and
thus may indicate either current or past infection. There is currently
no clinical indication for the use of HPV serology.