Human papillomavirus can survive months to years on surfaces.
21,24,25 Infection of a host requires direct contact with viral particles, which can occur through either direct contact via a plantar wart or indirect contact via fomites, such as flooring, socks, shoes, towels, and sports equipment.
4,23 There is no systemic dissemination or viremic phase to HPV infection. As such, contact with body fluids, except those directly from the plantar wart itself, does not transmit HPV.
14,21 Preexistent microtrauma of the epidermal barrier of the plantar aspect of the foot allows entry of the virus on contact.
5,26-29 Once in contact with a host, HPV gains entry to the basal epithelial layer, where actively dividing stem cells are located.
29,30 In the basal epithelium, the virus binds with cellular receptors and is subsequently taken up by the now-infected cell.
8,31 After an incubation period of 1 to 20 months, viral DNA is then established within the host cell, usually without integration into the host cell genome.
24,29,30
Once infection occurs, 3 outcomes are possible: clearance of the infection with resultant immunity to that particular HPV type, latent infection, or clinically manifested infection as a plantar wart.
4 After infection, if the virus is not cleared, the host basal keratinocyte is stimulated to divide and replicate viral DNA via HPV E1 and E2 proteins.
29,30 This process produces numerous stem cells that each contain 20 to 100 copies of the viral DNA.
11,29 The basal stem cells contain very low levels of viral proteins, which enhances the virus's ability to evade the host's immune response.
11,27,30 As the basal cells undergo normal differentiation into keratinocytes, they progress toward the outer surface of the epithelium. At the same time, the viral genome promoter region is activated, leading to increased production of viral proteins that enhance HPV genome amplification within each differentiating cell. It is thought that E5, a membrane protein produced via the viral DNA template, serves to enhance signaling from growth factor, which in turn maintains the cell's capacity for DNA replication.
29,30 Once viral DNA copies are sufficient, L1 and L2 viral coat proteins are expressed by surface keratinocytes.
11 Protein E2 recruits viral DNA copies to the host cell nucleus, where the viral DNA is packaged into capsids composed of proteins L1 and L2.
11,30 The infectious viral particles can then be released in high numbers from desquamated keratinocytes on the surface of the plantar wart to infect other sites or hosts.
8
The induction of cellular replication throughout the process of viral genome amplification leads to the hyperkeratinized papule that constitutes a plantar wart.
31 Plantar warts tend to develop at areas of increased pressure on the sole of the foot, including the heel and metatarsal heads.
5,25,27 Such pressure points are regions of increased microtrauma to the epidermal barrier, which increases the likelihood of HPV invasion.
15,26 Owing to the pressure exerted on the forming plantar wart, the lesion tends to progress deeper into the skin (creating an “iceberg effect”) as opposed to forming a rounded papule, which can contribute to their resistance to therapy.
1,26 As a result of normal sloughing of the epithelium, viral particles are released and may be transmitted to surfaces where the virus will lie until picked up by a new host or spread to adjacent sites (autoinoculation).
7,21 Thus, once a plantar wart develops, the host is susceptible to additional warts developing.
23
Sixty-five percent to 78% of cutaneous warts have been shown to regress within 2 years.
32 In persons older than 12 years, the rate of spontaneous regression significantly decreases.
2,33 Wart regression relies on the development of an effective cellular immune response.
8,34 However, plantar warts may develop in an otherwise healthy person when HPV gains entry to the epithelium and evades the host's immune response.
35 In the most healthy persons, HPV infections are controlled by an immune response that begins on contact with the HPV particle.
1,8,27 The viral antigen is first taken up by Langerhans cells of the epidermis, which then enter the regional lymphatic drainage and thereby enter a lymph node. There they present the antigen to T cells, which are activated and induce an antigen-specific immune response in the area of viral penetration. The antigen-presenting cells activate keratinocytes to release inflammatory cytokines that promote migration of neutrophils and monocytes, activation and migration of helper T cells, maturation of B cells, and activity of natural killer cells. Tumor necrosis factor α, which is released from keratinocytes, improves the recognition of virally infected keratinocytes by T cells, which are then responsible for destroying the infected keratinocytes.
8 This response should lead to eradication of the infection and prevent a plantar wart from occurring or lead to regression of established plantar warts. If this process fails, a persistent plantar wart is established.
36 Humoral immunity, if established by antibody-producing B cells, prevents future reinfection by that HPV type.
27