Human Papilloma Virus

Human papilloma virus (HPV) infections have two important clinical manifestations: external genital warts (EGWs) and squamous intraepithelial lesions (30). A discussion of these neoplasms is beyond the scope of this chapter but screening and treatment issues can be found elsewhere (2). The majority of newly acquired HPV infections are asymptomatic. EGWs are diagnosed when visible warts occur in the genital area; they can be discrete or coalesce into confluent plaques (30). The acetowhite test has not been definitely established as useful for diagnosis and has a low positive predictive value (30). Biopsy is seldom needed and is reserved for atypical lesions; uncertain diagnosis; progression of disease during treatment; warts that appear pigmented, indurated, ulcerated, or fixed to underlying structures; or warts that are >1 cm2.

An entire examination of the genitalia is warranted because EGWs frequently occur on multiple genital sites. Speculum examination assessing for vaginal and cervical warts is recommended for women with genital warts. Instrumentation (colposcopy, anoscopy, or urethroscopy) is recommended for women with cervical warts, men and women with recurrent perianal warts (history of anoreceptive intercourse), or men with warts at distal urinary meatus and terminal hematuria or abnormal stream (31). The differential diagnosis of EGWs is broad and includes normal anatomic structures, acquired conditions (e.g., molluscum contagiosum), and neoplasms such as vulvar neoplasia (2).

An estimated 24 million Americans are infected with HPV (1). Surveillance systems for HPV are rudimentary, and some experts estimate the incidence of HPV infections to be closer to 5 million per year (16). Genital HPV is transmitted primarily sexually; however, perinatal transmission can occur (laryngeal papillomatosis) (2). Immunocom-promised patients such as HIV-seropositive patients and renal allograft recipients are at high risk for genital HPV infection (30). An association between increasing number of sex partners and detection of HPV has been noted (32). There are inconclusive data on the association between smoking or estrogen stimulation (oral contraceptives or pregnancy) and HPV infection.

The 70 HPV genotypes are divided into low-risk types (including 6 and 11) and high-risk types (e.g., 16, 18, 31, 33, 35) based on their association with anogenital cancers (30). Visible EGWs are caused by types 6 and 11 and have been associated with conjunctival, nasal, oral, and laryngeal warts (2).

The primary goal of treatment of EGWs is to eliminate warts that cause physical or emotional distress (30). There is no evidence that treatment eradicates HPV or decreases infectivity (2). If left untreated, EGWs may resolve, remain unchanged, or increase in size. Patient education concerning such issues as HPV treatment and the association of certain types of HPV infection to cancers is essential. Patients should be cautioned that several treatment sessions are often required to achieve a wart-free state. After clearance, patients should be advised to watch for recurrences. Annual cervical cytologic screening is recommended for all women whether or not they have EGWs. The presence of genital warts is not an indication for colposcopy (2).

Treatment is divided into patient-applied (podofilox and imiquimod) and provider-administered (cryotherapy, podyphyllin resin, trichloroacetic, or bichloroacetic acid [TCA/BCA] interferon and surgery) therapies (see Table 4). Podofilox and podyphyllin are antimitotic agents. Imiquimod is an immune-response-enhancing agent that induces interferon a and other cytokines. Cryotherapy with liquid nitrogen causes cry-ocytolysis resulting in sloughing and wart destruction. TCA/BCA are caustic agents that destroy warts by chemical coagulation of proteins. Owing to low viscosity of these agents, care must be taken to prevent "running" of the solution onto unaffected areas (treated areas should be allowed to dry before the patient sits or stands). Surgical removal includes curettage, eletrocautery/electrotherapy, and ablative therapy (laser). Intralesional injections of interferon have been shown to be effective while systemic and topical treatments have not. Cidofovir and 5-fluorouracil (5-FU/ipinephrine/bovine collagen gel) implants are under development.

There are no guidelines regarding which treatment to use first. Treatment of EGWs should be guided by patient preference and the patient's ability to follow directions, number and location of warts, and clinical expertise (2). Experts suggest that treatment should be changed or the patient referred to a specialist when three treatment sessions have resulted in no improvement, if there is incomplete clearance after six treatment sessions or when continued treatment extends beyond manufacturer's recommendations (2,30). Clinicians must monitor patient progress and avoid overtreatment. Most experts agree that combining modalities on a single wart does not increase efficacy (2). All wart treatments may cause mild local irritation, ulceration, or erosion. Ablative modalities can result in hypopigmentation, hyperpegmentation, or hypertophic scars. Pregnancy and immunodeficiency are associated with larger or more numerous EGWs (30). There are reports of immunocompromised patients having EGWs with high-risk types of HPV (30,33). Although current treatments are imperfect, most patients can eventually be wart free. There is no reported resistance for genital HPV currently.

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