Excerpt from Papillomavirus

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Background

Infections due to papillomaviruses are common and lead to a wide variety of clinical manifestations that involve the epidermal surfaces. Manifestations include common warts (verrucae vulgaris), palmo-plantar warts, flat warts (verrucae plana), oral warts, focal epithelia hyperplasia, epidermodysplasia verruciformis (EDV), genital warts (condyloma acuminata), Bowen papulosis, Bowen disease, papillomas of the mucosal surfaces, and intraepithelial neoplasias. Strong evidence indicates that certain papillomaviruses are involved in cervical and genital cancers.

Pathophysiology

Papillomaviruses are small (55 nm) double-stranded DNA viruses. Papillomaviruses are widely disseminated in the animal kingdom, and more than 200 genotypes of human papillomaviruses that infect the skin and mucosal surfaces have been characterized. These viruses are highly species-specific. Papillomaviruses have never been grown in vitro but have been characterized by molecular methods.

The genome of papillomaviruses is approximately 8000 base pairs divided into 3 major functional regions. The early (E) region codes for 6 nonstructural genes, several of which are associated with cellular transformation. The late (L) region codes for 2 structural proteins, L1 and L2, that form the capsid. The long control region is a noncoding region that regulates replication and gene function.

These viruses are classified by the molecular similarity of their genetic material and are assigned a genotype number.

The viruses infect the basal keratinocyte of the epidermis, presumably through disruptions of the skin or mucosal surface. At this location, the virus remains latent in the cell as a circular episome in low copy numbers. As the epidermal cells differentiate and migrate to the surface, the virus is triggered to undergo replication and maturation and, at the keratinic layer, the virus is present in high copy numbers and is shed in the exfoliation cells. The process of virus replication alters the character of the epidermis, resulting in cutaneous or mucosal excrescences known as warts. Human papillomaviruses are broadly grouped into cutaneous and mucosal type, based on the clinical location of the lesion.

Although some overlap exists, most papillomaviruses have distinct anatomic predilections, infecting only certain epidermal sites, such as skin or genital mucosa. The virus has the potential to integrate into host DNA frequently with the loss of the early regulatory function. Numerous viral genotypes have the potential to transform cells and are associated with epidermal malignancies. This appears involve interactions of E6 and E7 proteins with host cell function. The mechanism for transformation is not known, but the viral DNA appears to integrate into the genome of the host cell.

Table 1. Association of HPV Types With Morphology and Site of Skin Lesions

Table 2. HPV Types Associated With Anogenital Lesions

Frequency

United States

The United States has no reporting system for papilloma infections. Infections and the development of warts appear to be common throughout life. In general, in the past several decades, the prevalence of genital papilloma virus infections is considered to have increased dramatically, and it is now one of the most common sexually transmitted diseases. The frequency of genital infections is associated with the number of sexual partners. In cervical neoplasias, the HPV genome can be detected in more than 90% of tumors.

Mortality/Morbidity

• Most common warts are of cosmetic concern and generally cause little problem unless their anatomic location induces mechanical problems. For example, plantar warts can disrupt ambulation because of their location. Laryngeal papillomas may disrupt breathing or speaking. Genital warts occasionally cause problems such as urethral obstruction. Condyloma acuminata can become extremely large, resulting in tissue breakdown or secondary infection. In the context of immune deficiency, such as HIV infection, the growth of warts due to papillomavirus can be augmented, significantly enhancing the associated anatomical problems.
• The major morbidity and mortality related to papillomavirus infections are due to the development of malignancies. Cervical cancer is the second most common cause of morbidity and death in women in the United States. Malignancies, such as Bowen tumors, may also lead to morbidity and death.

Race

Papillomavirus infections have no racial predilection.

Sex

Papillomavirus infections have no sexual predilection.

Age

People of any age may develop common warts. Human papillomavirus infects more than 50% of sexually active adults. Genital infection generally occurs during the sexually active period in a person's life, and infections increase with the number of sexual partners.

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