• • Gray or flesh-colored, pedunculated, and moist papules on the penis, urethra, vulva, cervix, anus, or perineal and perianal areas.
  
• • One or several grouped lesions may be present, ranging in size from a few millimeters to several centimeters.
  
• • Symptoms may include burning, itching, pain, and fullness (urethra, vagina, or anus); however, many patients are asymptomatic.

Human papillomavirus (HPV) is one of the most common sexually transmitted diseases (STDs) and is the cause of genital warts (condylomata acuminata), anogenital dysplasia, and invasive cancer. Oral warts may also occur as a direct consequence of HPV infection during sexual activity. At least 75% of sexually active men and women acquire one or more genital HPV types at some point in their lifetime. The incubation period from HPV infection to condyloma is usually 3–4 months, with a range of 1 month to 2 years, but many infected persons have subclinical disease or have regression of disease before it becomes clinically apparent. HIV-infected patients have a higher prevalence of genital warts than HIV-uninfected patients. These may proliferate further during immune reconstitution following the initiation of antiretroviral therapy.

There are more than 100 different HPV types; 40 of these can cause anogenital lesions. HPV types 6 and 11 are most commonly associated with genital warts; these types have a low risk of malignant transformation. Other types (eg, 16, 18, 31, 33, and 35) have a strong association with cervical and other anogenital cancers. Thus, genital warts lie on one spectrum of a continuum of HPV-associated disease, with warts being one variant of low-grade disease that has little risk of malignant potential. High-grade HPV-associated disease such as cervical intraepithelial neoplasia (CIN) types 2 and 3 are likely the direct precursors to invasive cancer and are the target of screening programs that utilize the Papanicolaou (Pap) test.

Most anogenital HPV is believed to be acquired via sexual transmission. Following acquisition of infection, HPV infection is established initially in the basal cells of the anogenital epithelium. As the basal cells differentiate and rise to the epithelial surface, HPV replicates and virions form. A spectrum of disease occurs, depending on the degree of mitotic activity and replacement of the epithelium with immature basaloid cells. In the cervix, this ranges from genital warts or mild dysplasia (CIN 1) to moderate or severe dysplasia (CIN 2 and CIN 3).

The most reliable method of preventing HPV acquisition is abstinence from sexual activity, including skin-to-skin contact. However, there is strong evidence that male latex condoms offer some protection against HPV infection, as well as HPV-associated diseases such as genital warts, CIN 2 or 3, and invasive cervical cancer. Although not recommended by the US Centers for Disease Control and Prevention (CDC), partner evaluation may offer an opportunity to screen and provide education on HPV and other STDs.

Preventive vaccines are promising new options. A multivalent vaccine against four HPV subtypes (6, 11, 16, and 18) was approved by the Food and Drug Administration (FDA) for use in women and girls aged 9–26 years in June 2006. These immunizations use components of the major HPV capsid proteins that assemble into viruslike particles that contain no HPV DNA and thus are not infectious. Vaccination with viruslike particles is designed to induce neutralizing antibodies prior to initial HPV exposure by the host. In large, randomized controlled trials, excellent efficacy has been demonstrated against certain HPV types, including 6, 11 (which can cause anogenital warts), and 16 and 18 (which can cause invasive cervical and other anogenital cancers). Future trials will test the efficacy of combined vaccines for additional types.

Symptoms and Signs

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.

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