Verruca HPV and the Immune System
The common plantar verruca, also termed viral plantar wart and verruca vulgaris is caused by the double stranded DNA Human Papilloma Virus (HPV). The genome has approximately 8000 base pairs. It is part of a large family of over 200 identified viruses with cervical cancer and genital warts being included. The common HPV sub types for the verruca are HPV 2 and 4. Sub types 1, 3, 26, 29, and 57 have also been identified to cause a papilloma infection, with new strains being identified all the time. They all have a distinct profile. The verruca HPV is a ‘low risk’ type which produces a benign growth (papilomma) with the chances of malignant changes being rare.
Palmar warts appear on the hand. Plantar warts affect the feet.
How do you catch the virus?
The virus is contracted by coming into direct contact with viral particles (virions) which have been left by another infected foot or hand. These commonly are left in warm moist communal areas like showers, swimming pools and gyms, but hypothetically could be caught by simply trying on a shoe in a shoe shop which has just been tried on by an infected individual. It can be very contagious. The virus enters the skin’s epithelium.
The integrity of the skin plays an important deciding etiological factor in whether individuals are more susceptible to contracting the virus. If the skin is macerated from increased water content it creates an ideal environment for entry and spread. Skin subject to repetitive micro-trauma from sport, or a prominent weight bearing point of the foot e.g. a pronounced metatarsal joint, is subject to increased mechanical stress.
In clinic occasionally, individuals have been seen to have a verruca entrenched next to a corn. This can confuse diagnosis.
How does the verruca virus enter the skin?
The virus moves undetected by the immune system through the epithelial cells to enter a cell’s nucleus whereby it rapidly replicates approximately 10 – 200 times, meaning there will be multiple viral genomes. The virus is specific to the skin and will not enter and replicate in live tissue. Verrucae are only ‘skin deep’ and do not have ‘roots’, which invade deeper into the body’s subcutaneous layers.
What is the incubation time?
How quickly a verruca virus ‘takes hold’, to start producing a papilloma growth, depends on the HPV sub type and the health of the individual predominantly the strength of their immune system. The virus once it has entered a cell can remain dormant up to a year, hence many individuals cannot recall where they ‘caught it’.
Why does the immune system not destroy it?
The verruca HPV virus is very clever it can literally go under the radar. In most viral infections when virions enter a cell to cause damage they stimulate the production of cytotoxic T-cells. Think of T-cells being like an army which seeks out and destroy invaders once the alarm flag has been raised. In the case of a verruca no alarm flags get raised. The HPV is concentrated in the skin’s upper shedding epidermal layers so does not produce viral particles deeper down to alert the immune system. The lack of circulating antigen presentation therefor does not trigger an immune response.
To complicate matters further, the HPV proteins are cleverly encoded with specific instructions to be invisible. They activate T-suppressor cells to inhibit an anti-inflammatory response. The virus is the ultimate stealth parasite which decides when it wants to ‘leave’, resolve, which can be anywhere between several months to years. Many patients report having had the same verruca for ‘years’. One patient presenting at our clinic had the same treatment resistant verruca for over 15 years. Why is this? Read on.
Why are some people more susceptible to getting verrucae and warts?
We have already discussed risk factors like walking into infected communal areas, but you can have 5 individuals using the same space and only 1 or 2 get infected. Is this pot luck? No, it appears that some individuals are more susceptible than others with having a lower natural immunity. It does not necessarily mean they have a bad immune system, but potentially are missing the protective genome against the virus? This needs to be studied further.
Another question to be answered and an important area of study, is why do some individuals constantly seem susceptible to getting an infection despite having had an infection before? Is it because they have never developed antibodies against it? This leads us on to the next question.
Does the verruca virus completely go after an infection has resolved?
Many HPV strains can remain dormant in the body long after an infection has occurred and has resolved, then reappear later, much in the same way as Herpes Simplex (Cold Sore). Does this happen with the verruca HPV? There are studies done researching into cervical cancer and immunity, which demonstrate only 50–60% of women develop serum antibodies to HPV after an infection.
Anecdotally many adult patients who get verrucae report having had a stubborn verruca in childhood. This is hard to prove that there may still be some viral elements left behind. Costly genetic profile scanning for traces of the HPV would have to be undertaken regularly from childhood right up into adulthood to validate this. Interestingly very little research is concentrated on the verruca virus. It is the high risk cancerous ones which rightly require the attention and for which vaccinations are developed.
Why do some people respond better to treatment than others?
Children tend to respond very quickly to verruca treatments. They tend to get an early cell mediated response. Is this because their immune systems are better than adults? Children’s immune systems are in a state of constant development, building up natural immunities to common viruses which could mean they establish immune recognition earlier for rapid resolution? By the age of 20 the immune system is pretty much established, with some having a better immune system than others to combat HPV infections.
Why are verrucae viruses hard to treat?
Treating verrucae is challenging for podiatrists when the virus has mechanisms to evade the immune system. The virus creates a pro-inflammatory microenvironment. The T-suppressor cells hinder treatments which are designed to mediate an immune response by causing an inflammatory response through tissue irritation and destruction. There is then the added problems of dormant viral particles laying latent adjacent to an infection waiting to spring into action when they so choose!
Can treatments make verruca infections worse?
Treatments can inadvertently cause collateral damage and increase the area of infection spread by pushing these latent virion particles outwards. Acid treatments can be the worst culprit of all. They can result in uncontrolled skin damage. They break down the skin’s protective barrier.
Treatments which have a more controlled delivery method directly target the verruca. They cause less collateral skin damage to reduce the risk of increasing area of infective spread. The Swift microwave and the Nd:YAG laser directly target verruca tissue, although there is the danger of resulting blisters pushing viral particles outwards. Care must be taken by the podiatrist to ensure this does occur post treatment.
What can be done to boost the verruca immune response?
Diet and nutrition play an important and influential role in boosting the immune system. A diet that is deficient in certain nutrients could be detrimental, or one that is high in processed fats, sugar, caffeine and alcohol. They put additional pressure on the immune system by stressing the liver. This is because these foods contain plentiful amounts of inflammatory chemicals which will motivate your immune system to try and produce more histamine, eventually exhausting your immune cells, making them more sluggish and considerably less effective at protecting your body against viral infection.
Does taking medication effect the body’s immunity in getting rid of verrucae?
Yes. If you are taking medication which is anti-inflammatory like steroids you are suppressing the body’s natural immune responses. The drug methotrexate which is used in the treatment of rheumatoid arthritis, can suppress the immune system as does prednisolone, corticosteroids.
What conditions can make you more susceptible to getting a verruca?
Generally, all conditions which put additional stress on the body’s immune system will potentially make it easier for the verruca virus to get in by the ‘back door’. Having an auto-immune condition like arthritis, psoriasis and eczema, will suppress the immune system. The body’s immune proteins (interleukins) which help to fight off bacteria and viruses mistakenly target the body’s own tissues to cause unwanted and damaging autoimmune reactions. To complicate matters, steroids are prescribed to counteract the pain and inflammation, which in effect suppresses the immune system. You just can’t win!
Does having Hayfever affect the immunity against getting a verruca?
Having a hypersensitivity like hayfever, can dampen the body’s immune system too. The body’s immune system goes into overdrive in an attempt to fight ‘an invader’ which it mistakenly believes is harmful, but in reality is innocuous. Again being prescribed steroids or anti-histamines dampens the body’s immunological responses. If the HPV virus is lurking somewhere, being an opportunist, it can seize the chance to hop on board.
Is stress a factor in getting a verruca and can it affect treatment?
Yes. Just even having a nasty verruca infection can cause stress, which can impede treatment efficacy. Stress puts a huge strain on the immune system. It triggers release of inflammatory chemicals and redirecting the flow of nutrients from critical parts of the body, like your skin, to your major organs. Emotional distress can even upset the digestive system, causing constipation and inhibiting the liver from detoxifying your body, forcing other organs, including your skin, to take over the duty. The skin can become weaker, allowing the HPV virus to permeate your epidermis and stimulate an episode and impede treatment once you have an infection.
Does having an immune system issue mean I will never get rid of my verruca?
The simple answer here is it depends on the severity of your immune issues and the medication you are taking. In the case of the lower severity conditions, the podiatrist will have to work a lot harder with the patient to get a successful outcome. It could take much longer, so more patience is required on both sides. It really is important to modulate patient expectations.
Are there other factors which effect the success of a verruca treatment?
Yes. A person may simply be missing the genome which gives them the immunity to the virus and they never develop an immune response. This does not mean a person has a poor immune system and there is no way for the podiatrist on presentation of a verruca infection to know if this is the case. It often becomes apparent when all forms of treatment fail.
The Swift microwave treatment protocols advise not to treat patients who have immune issues. These are not always apparent even after a thorough consultation. It is only after a treatment failing that this could be considered to be a hindering factor.
What is the future in treating treatment resistant verrucae and warts?
Much more works needs to be done looking at the HPV strains which cause verrucae infections and verruca immunity. There are already developed and used vaccines which protect individuals against some high risk HPV strains. These vaccines stimulate cell-mediated immune responses in the presence of HPV. What we now need is to develop one for the common verruca.
There have been clinical trials undertaken whereby other prophylactic vaccines such as the MMR vaccine are injected into the verruca to mediate an immune response. Intralesional antigen immunotherapy has shown promising efficacy in the treatment of treatment resistant warts.
FURTHER READING:
- https://www.forbes.com/sites/quora/2017/01/30/are-allergies-a-sign-of-a-weak-immune-system/#38b3128e5beb
- Treatment of recalcitrant warts with intralesional measles, mumps, and rubella vaccine: a promising approach. Nofal A et al: Int J Dermatol. 2015 Jun;54(6):667-71
- Human Papillomavirus (HPV) Infection: https://www.ncbi.nlm.nih.gov/books/NBK321770/:
- The Treatment of Verrucae Pedis Using Falknor’s Needling Method: A Review of 46 Cases: Belinda Longhurst, Ivan Bristow;J Clin Med. 2013 Jun; 2(2): 13–2
- Role of Innate Immunity against Human Papillomavirus (HPV) Infections and Effect of Adjuvants in Promoting Specific Immune Response: Alfredo Amador-Molina et al; Viruses. 2013 Nov; 5(11): 2624–2642
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