Human Papillomavirus

Human papillomavirus (HPV) belongs to the Papovaviridae family of double-stranded DNA viruses. Transmission of genital HPV occurs through skin-to-skin contact. There are more than 200 HPV types identified by PCR techniques. Different HPV types have preferences for different body tissues, with some types preferentially affecting the mucosa, others affecting thinner keratinized skin such as lower legs or dorsal hands, and still others found primarily on palms and soles.

Common, plantar, and flat warts are examples of extragenital skin lesions. Genitomucosal lesions can be associated with significant clinical disease. HPV types 6 and 11 are most often associated with benign disease or low-grade cervical intraepithelial neoplasia. High-grade cervical intraepithelial neoplasia (CIN), cervical squamous cell carcinoma, vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, penile cancer, and anal cancers are traditionally associated with high-risk HPV types 16 and 18. Although 50% of the reproductive age population exhibits signs of exposure to HPV infection, only 1% to 2% of the adult population actively manifests clinical genital warts (11,12). Identifiable risk factors for genital warts and cervical dysplasia include multiple sexual partners, sexual activity at an early age, history of other sexually transmitted diseases, age of first pregnancy, previous abnormal Pap smear, cigarette smoking, poor diet, poor hygiene and immuno-compromised state. Patients with an immunocompromised state often have genital warts that are resistant to treatment. While infection with HPV is strongly linked to cervical dysplasia and invasive cervical cancer, other factors are important as well. Other factors such as immune status and environmental factors are important in the development of cervical neoplasia.

Most HPV infections are temporary and asymptomatic, although occasionally large warts can produce irritation from fissuring or itching. Genital warts can present as a single or multiple papules on the penis, vulva, vagina, cervix, or perineum, on any skin covered by a bathing trunk. Additionally, lesions can extend into the urethra or rectum. Lesions are flesh colored, hyperpigmented, or pink. Otherwise, the morphology varies from acuminate, or pointed (the classic condyloma acuminatum), to flat-topped, to ver-rucous, and to cauliflower appearance with a narrow or broad base (Fig. 5). The lesions vary in size and often coalesce with fusion at the base. Flat, pigmented lesions are the warts that most often exhibit vulvar intra-epithelial neoplasia (VIN) 3 on biopsy, although naturally darkly complexioned patients regularly exhibit benign hyperpigmented warts.

Most lesions are self-limited in the immunocompetent patient and often resolve spontaneously. During pregnancy, lesions may increase in size and number. Patients with condylomata acuminata have an increased risk of HPV-associated cervical pathology. Persistent HPV can be associated with increased age or HPV types 16 and 18. Although genital HPV lesions acquired perinatally can appear in children up to about three years of age, sexual abuse should be considered and children at risk should be evaluated.

Cervical dysplasia is generally not visualized on examination. Evidence of moderate-to-severe dysplasia may be evident on colposcopy by punctuation or mosaicism, or acetowhite changes after treatment with acetic acid.

Mollusca contagiosa, nevi, sebaceous hyperplasia, vulvar papillomatosis, and epidermal cysts are lesions most often mistaken for genital warts. Genital warts are generally diagnosed by physical examination alone, but a biopsy to confirm

Hyperpigmented Labia

Figure 5 Genital warts can exhibit any of several morphologies. These papillomatous and flat lesions are characteristic, and the hyperpigmented nature in a light-complexioned patient should raise the suspicion of vulvar intraepithelial neoplasia, which was not present in this woman.

the diagnosis is indicated in atypical cases, and reveals the presence of koilocytes in the superficial malpighian and granular layer.

Cytologic findings on pap smear often guide the management of patients with cervical dysplasia. HPV DNA testing using hybrid capture techniques can be performed at the time of a pap smear to look for specific HPV high-risk types.

The management of genital warts includes patient education regarding the nature of genital warts, transmission, and treatment issues, as well the increased risk of cervical carcinoma. Although in the past many clinicians sought evidence for HPV in male partners to prevent reinfection, newer evidence does not indicate that a careful search is fruitful or helpful (13). Frequent Papanicolaou smears are indicated, and warts suspicious for vulvar intraepithelial neoplasia should be biopsied. There is no ideal therapy for anogenital warts, as evidenced by the very large number of treatments and treatment regimens (14). Treatments for genital warts include destructive therapies performed in the office, such as cryotherapy, excision, podophyllum resin, trichloroacetic and bichloroacetic acid, and laser (14). Home therapy with podofilox or the immune enhancer imiquimod can also be used. Because imiquimod exerts its effect at least partly by enhancing the immune system, recurrences are fewer (15). Local injections of alpha interferon are useful in some. However, recurrence following treatment is usual, and several courses of therapy are often required for definitive removal. Patients who are immunosuppressed present greater difficulties because elimination of the virus depends upon an intact immune system. Those patients with HIV treated with highly active antiretroviral medications respond much better to therapy for their genital warts than those not on medication for HIV (16).

Vaccines are under investigation, with one showing a beneficial effect for HPV 18 in women. Some reviews suggest that many are late in investigation showing promise as safe and effective prevention, while other reports describe safety but no evidence for efficacy (Table 3) (17,18)a.

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