Papillomaviruses are nonenveloped viruses of icosahedral symmetry with 72 capsomeres that

surround a genome containing double-stranded circular DNA with approximately 8000 base
pairs. Their genome is divided into the following 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

Papillomaviruses are highly species-specific and do not infect other species, even under
laboratory conditions. Humans are the only known reservoir for HPV. Papillomaviruses have
never been grown in vitro but have been characterized by molecular methods. These viruses are
classified by the molecular similarity of their genetic material and are assigned a genotype
number.
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.
HPV infects 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. Autoinoculation of virus into opposed lesions is common. Spread of HPV
infection is usually through skin-associated virus and not blood-borne infection. Cell-mediated
immunity (CMI) probably plays a significant role in wart regression; patients with CMI
deficiency are particularly susceptible to HPV infection and are notoriously difficult to treat.[12]
Papillomaviruses are thought to have 2 modes of replication:

Stable replication of the episomal genome in basal cells

Runaway, or vegetative, replication in more differentiated cells to generate progeny virus

As the epidermal cells differentiate and migrate to the surface, the virus is triggered to undergo
replication and maturation, and at the keratitic 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.
Note the figures below detailing the mechanisms of action for HPV.

The left panel is transudation of

serum antibodies to the site of human papillomavirus infection, and the right panel is exudation
of serum antibodies to the site of human papillomavirus infection.

The figure shows proposed

mechanisms used by the human papillomavirus vaccine to neutralize antibodies and protect
against infection.

Figure showing how human

papillomavirus penetrates the basal layer and eventually is released at the surface.
Although all cells of a lesion contain the viral genome, the expression of viral genes is tightly
linked to the state of cellular differentiation. Most viral genes are not activated until the infected
keratinocyte leaves the basal layer. Production of virus particles can occur only in highly

differentiated keratinocytes; therefore, virus production occurs only at the epithelial surface
where the cells are ultimately sloughed into the environment.
HPV infections have not been shown to be cytolytic; rather, viral particles are released as a result
of degeneration of desquamating cells. The HPV virus can survive for many months and at low
temperatures without a host; therefore, an individual with plantar warts can spread the virus by
walking barefoot.
Viral multiplication is confined to the nucleus. Consequently, infected cells exhibit a high degree
of nuclear atypia. Koilocytosis (from Greek koilos empty) describes a combination of
perinuclear clearing (halo) with a pyknotic or shrunken (raisinoid) nucleus and is a characteristic
feature of productive papillomavirus infection.
Numerous viral genotypes have the potential to transform cells and are associated with epidermal
malignancies. In benign or low-risk HPV lesions, such as those typically associated with HPV
types 6 and 11, the HPV genome exists as a circular episomal DNA separate from the host cell
nucleus. In malignant lesions, the genomes of high-risk HPV types 16 and 18 are typically
integrated into the host cell DNA. Integration of the viral genome into the host cell genome is
considered a hallmark of malignant transformation.
HPV proteins E6 and E7 of high-risk serotypes have been shown to inactivate the hosts tumor
suppressor proteins p53 and Rb, thereby resulting in unregulated host cell proliferation and
malignant transformation.