Human papillomavirus (HPV) infection is the most common sexually transmitted disease (STD) in the United States. An estimated 5.5 million to 6 million cases are diagnosed annually, and approximately 20 million people have detectable HPV DNA.1-3 About 75% of sexually active people aged 15-49 have been exposed to HPV or show evidence of previous exposure.4,5 Sensitive amplification techniques have found the prevalence of HPV DNA to be 2.8%-57% in the immunocompetent female population.4,6 Despite these statistics, in a survey of Americans 18 years or older, 70% had never heard of HPV.7

Although most people are exposed to HPV shortly after their first sexual experience, in the majority of cases, genital warts or squamous intraepithelial lesions do not develop.8 HPV infections are usually asymptomatic, subclinical, and unrecognized. In fact, many people do not know they are infected, and they can easily transmit this infection to others.9

What is HPV?

Papillomaviruses are a group of small DNA viruses with the ability to turn off tumor-suppressing genes, thereby inducing replication of the tumor’s DNA. This primarily results in evoking epithelial cell proliferation, or papillomas.10 Papillomaviruses cannot be efficiently grown in tissue culture, and little is known about their life cycle.9

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There are more than 100 different types of HPV, 30 of which are associated with infection of the genital tract.4,9 Clinical manifestations are varied and may present as condyloma acuminatum (genital warts); Pap smear abnormalities; cervical, vulvar, anal, and penile cancers; and rarely, respiratory papillomatosis in infants and children.4,9

While the presence of HPV is necessary in the development of cervical cancer, most infections will not cause significant cervical disease.4,6,9 Persistent infection with “high-risk” types of HPV (e.g., 16, 18, 31, 33, 35, 39, 45, 51, and 52) is associated with cervical and anal cancers. “Low-risk” types (e.g., 6, 11, 42, 43, and 44) are usually associated with benign lesions and rarely linked with squamous cell carcinoma (SCC).4-6,9 The rates of HPV infections in prospective studies of young women decrease over time, with most clearing the virus in one to two years.6,11

How is HPV transmitted?

HPV is easily transmitted by skin-to-skin contact during oral, vaginal, or anal intercourse with an infected partner.9 While infections in virgins are rare, nonpenetrative contact has been associated with increased risk.12

Even though precise risk factors for HPV infection are not well known, chances of contracting the virus are increased with immunocompromised states, smoking, pregnancy, co-infection with other STDs, use of oral contraceptives, number of sex partners, ethnic minority, and younger age. 4,9,12

HPV and genital warts

Visible genital warts are usually caused by low-risk types of HPV (specifically types 6 and 11). The lesions can occur anywhere on the external genitalia as well as the cervix, vagina, urethra, anus, and even the mouth The presence of genital warts is not associated with an increased risk of cancer in the future.9 Intra-anal warts are seen predominantly in patients who have had receptive anal intercourse.

Depending on the size and anatomic location, genital warts can be painful, friable, and pruritic, although they are usually asymptomatic. Lesions may range in color from hyperpigmented to flesh- or pink-colored papules or plaques that may coalesce to form vegetative forms (cauliflowerlike growths). They can spontaneously regress, increase in size, or persist for years.

Low-risk HPV types 6 and 11 have also been associated with conjunctival, nasal, oral, and laryngeal warts. Information about HPV’s link to cervical cancer is presented later in this article.

Diagnosing genital warts

While diagnosis can be confirmed by biopsy, microscopic examination is needed only under certain circumstances, such as when the diagnosis is uncertain, the lesions do not respond to standard therapy, the disease worsens during treatment, the patient is immunocompromised, or the warts are pigmented, indurated, fixed, and ulcerated. No data support the use of type-specific HPV nucleic-acid tests in the routine diagnosis or management of visible genital warts. 

An infection is considered subclinical when there is no evidence of genital lesions or squamous intraepithelial lesions (SILs). Subclinical infections may be detected by Pap smear, colposcopy, or biopsy; by the appearance of a white area on the penis, vulva, or other genital skin following application of acetic acid; or by positive HPV DNA detection on any genital skin. No known therapy eradicates subclinical infection.

Screening for subclinical genital HPV infection using DNA or RNA tests is not recommended, nor is the routine use of acetic acid solution (3%-5%) on genital skin because the sensitivity and specificity have not been determined for HPV.9

Treatment is not recommended for subclinical HPV infection diagnosed by colposcopy, biopsy, acetic acid application, or the detection of HPV by other laboratory methods in the absence of SIL or other manifestations. If an SIL develops, management should be based on histopathologic findings.9

Sex partners of those diagnosed with genital warts may benefit from examination for warts and other STDs. There is no evidence that re-infection plays a role in recurrences.4,9