(Version Complète en Anglais)
The cause of plantar wart is not a single virus but a group of non-enveloped viruses that are categorised into more than 150 types according to their similarities in DNA sequencing, being subsequently classified into species of 1 to 5 genera: α, β, γ, µ, and ν[i].
HPV species already isolated in plantar warts include HPV-1, -2, -3, -4, -27, -29, -57, -60, -63, -65, -66, and -69, of which 88 % are associated with types 1, 2, 27 and 57, with type 1 being the most distinct in terms of clinical profile[ii].
Transmission takes place through direct contact with viral particles.
Epidemiology and Risk Factors
It is estimated that about 40% of the population is infected with HPV but only 7 to 12% will develop plantar wart[iii].
This exhibits an annual incidence of about 14% and the most commonly identified risk factors are:
- Prolonged exposure to HPV
- Tissue damage/weakness of the epidermal barrier
- Impaired/diminished immune response
The incidence varies according to gender, age, race and health status, but is also influenced by geographic location, seasonality, behavior and socio-economic factors, although its higher incidence is clearly during the cold and humid winter months.
Plantar Wart – Physiopathology
HPV can survive on surfaces for many months[iv]. The host infection process occurs either through direct contact with the plantar wart or through indirect contact via fomites (passive vectors), such as the floor, socks, towels, sports equipment, etc.
In this type of contagion, HPV does not have a viraemic phase or systemic dissemination, and therefore contact with body fluids (except for those emanating from the lesion itself) does not transmit the virus[v].
The existence of a continuity solution in the skin (a wound or microtrauma) allows the entry of the virus[vi] which, when in contact with the host, penetrates the basal epithelial layer where the stem cells are in division[vii]. It is in this environment that the virus binds to cell receptors and enters cells, which become infected[viii].
After an incubation period of 1 to 20 months, the viral DNA establishes itself within the host cell, usually without integration into its genome, and the infection is installed[ix].
Once the infection occurs, one of 3 situations is expected:
- Clearance of infection – immunity to this particular type of HPV
- Latent infection
- Clinical manifestation – plantar wart[x]
If the infectious process occurs without clearance, the basal keratinocyte is stimulated to divide and replicate the viral DNA via HPV E1 and E2 proteins, a process that produces several stem cells, each of which contains between 20 and 100 copies of the viral DNA[xi].
The cells themselves contain low levels of viral protein which allows the agent to evade the immune response.
As basal cells differentiate into keratinocytes, they progress towards the epithelial surface at the same time as the viral genome promoter is activated, increasing the production of viral proteins that potentiate HPV genomic amplification between each of the cell differentiation phases. It is possible that the E5 membrane protein produced via viral DNA serves to potentiate growth factor signaling, which, in turn, enables cellular DNA replication.
Once the viral DNA copies are sufficient, the viral capsular proteins L1 and L2 are expressed on the surface of the keratinocytes[xii].
E2 proteins recruit copies of viral DNA to the nucleus, where it is wrapped in capsids composed of L1 and L2 proteins, and these particles can be released in large quantities through the keratinocyte desquamation, thus potentiating the infection of other hosts[xiii].
The induction of cell replication through the viral genome amplification process leads to a hyperkeratinized papule characteristic of plantar warts, which tend to develop in areas where the foot is under greater pressure, such as the metatarsal heads and heel. It is these pressure points that potentiate the microtrauma of the epidermal barrier, which increases the possibility of invasion by HPV.
It is also due to the action of this pressure that the lesion tends to progress toward the interior of the skin (the so-called « iceberg effect») instead of forming only an external papule, which is one of the main reasons for resistance to treatment[xiv].
As a result of the normal shedding of the epithelium, viral particles are released and can be transmitted to surfaces, where the virus will remain until it is picked up by a new host or spread to adjacent sites (autoinoculation). Thus, once a plantar wart develops, the host is susceptible to developing additional warts[xv].
Sixty-five to 78% of cutaneous warts regress within 2 years[xvi] however, in individuals older than 12 years, the spontaneous regression ratio decreases significantly[xvii].
Wart regression depends on the development of an effective cellular immune response[xviii]. However, the ability to evade the host’s immune system means that even healthy individuals can be infected[xix].
In most healthy people, HPV infection is controlled through an immune response that is initiated upon contact with viral particles. The viral antigen is verified by Langerhans cells, which migrate to the lymphatic system and later reach a lymph node where they present the antigen to a T lymphocyte, which is activated and induces a specific response in the area of viral contact. Antigen-presenting cells activate keratinocytes to release inflammatory cytokines and promote the migration of neutrophils and monocytes, as well as the activation and migration of Th lymphocytes, the maturation of B cells, and natural-killer (NK) cell activity.
Keratinocytes release tumour necrosis factor α, which enhances the recognition of infected keratinocytes by T lymphocytes, which destroy the infected keratinocytes. This is the response that causes the eradication of the infection and prevents the appearance of the lesion/wart and/or its regression, forming B cells that produce specific antibodies, responsible for the humoral response. It is when this process fails that the wart develops.
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