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Diagnosis: Human Papillomavirus

Filippone, Lisa M. MD

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Dr. Filippone is an assistant professor of emergency medicine at Drexel University College of Medicine and the director of the Division of Emergency Ultrasound at Mercy Hospital of Philadelphia.

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This patient has an extensive oral infection caused by human papillomavirus (HPV). He also is infected with human immunodeficiency virus, and according to his last CD4 count, has acquired immunodeficiency syndrome. Patients with HIV who are infected with HPV are difficult to manage. Because of their inability to mount an effective immune response against HPV infection, the clinical manifestations are severe. Standard therapy for HPV is often not efficacious. Referral to an infectious disease specialist and a dermatologist is required to help control his HIV infection and minimize the concurrent HPV infection.

Human papillomavirus is a double-stranded DNA virus of the papillomaviridae family of viruses. They consist of more than a hundred genotypes with varying oncogenic potential. Subtypes 16, 18, and 31 are associated with the highest risk of malignant transformation. Infection with HPV may result from direct person-to-person transmission, contact with a contaminated object, vertical transmission, or contact with the virus in the environment. HPV can survive for months at low temperatures without a host. Infection usually takes place via contact of the virus to abraded skin or during sexual activity. HPV infects the host's basal cells. As these cells become differentiated as they move toward the skin surface, viral genes are activated and viral particles are produced. As a result of the natural degeneration of desquamating cells, viral particles are released at the skin surface and into the environment.

HPV infection may be latent, subclinical, or clinical. In latent infection, viral DNA is present in tissue, but complete viral particles are not assembled. The virus is only identified by techniques such as PCR or DNA hybridization. Subclinical infection is characterized by the presence of viral proteins and infectious particles, and can be identified by microscopy or colposcopy. Clinical infection is identified by visible skin changes, which are seen with the naked eye.

The clinical spectrum of HPV infection can be classified in many ways. The simplest classification system I have seen is found in the American Academy of Dermatology's Committee on Guidelines of Care for Warts. (J Am Acad Derm 1995;32[1]:98.) They classify lesions according to the clinical location and morphology. In general, there are three categories: cutaneous, anogenital, and extracutaneous.

Cutaneous lesions include the common wart (verrucae vulgares), flat warts, plantar and palmar warts, and mosaic warts. Anogenital lesions include the cauliflower-like growths referred to as condylomata acuminata as well as subclinical lesions. Bowenoid papulosis also is included in this category, and refers to a flat-appearing lesion, which has histological features of intraepidermal squamous cell carcinoma. Extracutaneous lesions include those found on the conjunctiva, within the oral cavity and sinuses and laryngeal papillomatosis (lesions may extend into the bronchial tree). Special mention must be made of the inherited disorder epidermodysplasia verruciformis. In this rare condition, patients have a genetic defect in their cell-mediated immunity that results in infection with HPV and often with uncommon subtypes. They have an increased risk of malignant transformation particularly of those lesions present on sun-exposed areas.

There is no definitive therapy for HPV infection, and recurrence rates are high. Spontaneous regression of infection is not uncommon. This is particularly true of cutaneous lesions, in which 60 percent to 70 percent of lesions will resolve within two years of appearance. Anogenital warts are less likely to resolve spontaneously. Treatment of HPV infection depends on the location and extent of the lesions. Treatment modalities can be classified into several following categories: cytodestructive, antimetabolic, antiviral, and immune modulators.

Cytodestructive therapy is the most diverse category. Cryotherapy with liquid nitrogen is commonly used for anogenital and cutaneous warts. It is best for limited disease. Side effects include pain, blistering, and skin discoloration. For more extensive disease, carbon dioxide laser therapy is a better option. Bichloroacetic acid and trichloroacetic acid can be applied topically and destroy warts by coagulation of cellular proteins. Podophyllin and podophyllotoxin are mitotic poisons, and are used topically for anogenital warts. The most common over-the-counter medication for the treatment of cutaneous warts is salicylic acid. When applied topically, it aids in the removal of excessive keratin. Finally, either conventional surgery or electrosurgery may be needed for refractory lesions.

The main antimetabolic treatment used is 5-FU. It is applied topically or injected into the wart, and destroys the lesion by inhibiting DNA synthesis and RNA function, disrupting cell division. It is used for the treatment of anogenital warts, and common side effects are pain and ulceration.

Cidofovir is an antiviral nucleoside analog that may be useful for treating anogenital warts, but further study is required.

The most commonly used immune modulation therapies are imiquimod and interferon. Imiquimod is applied topically, and induces production of alpha and gamma interferon and interleukin 1, 6, and 8, enhancing cell-mediated activity against HPV. Intralesional injection of alpha interferon also stimulates cell-mediated immunity and induces antiviral protein synthesis.

A vaccine for the prevention of HPV-16 infection, a high-risk genotype for cancer, is currently undergoing clinical trials. Until a safe and reliable vaccine is ready, focus must be paid to prevention. Unfortunately, traditional safe-sex methods are less helpful in the prevention of anogenital warts. Infection can be transmitted during foreplay and during nonvaginal sex. The spermicide nonoxynol-9 is not active against HPV, but detergents such as sodium dodecyl sulfate (SDS) are effective against HPV, and can be used in combination with a spermicide.

© 2004 Lippincott Williams & Wilkins, Inc.