Cryosurgery is a method of selectively destroying unwanted tissue using cold liquids or gases. The aim is to cause maximum tissue destruction in the target lesion with minimal collateral damage to the surrounding healthy structures. Cryosurgery does not kill the wart virus; in fact viruses can survive and be preserved in liquid nitrogen. What we are trying to do with cryosurgery is to destroy the cells that are infected with the wart virus by creating intracellular ice crystal formation that ruptures the cell, thus allowing clean, healthy, uninfected cells to take their place. 

Post-cryosurgery there is a lot of swelling which blocks the small feeding vessels causing ischaemic necrosis to the frozen area, enhancing cell death. In addition, cryosurgery has the unique action of ‘cryoimmune stimulation’, whereby some of the wart virus is released from the frozen wart after cryosurgery, presenting wart antigen to the immune system. This acts like a vaccine, helping the body to fight off the human papillomavirus (HPV) in the treated and sometimes even distant untreated warts. Patients who have a suppressed immune system are less likely to benefit from ‘cryoimmune stimulation’. Combining imiquimod (Aldara) with cryosurgery may enhance this response.¹

There is only one important rule in cryosurgery: never freeze any lesion unless you are 100% sure of the diagnosis. If you cannot make a confident named clinical diagnosis, do not freeze – take a biopsy or refer the patient for another opinion.

Success in cryosurgery is dependent of four main factors: cryogen, delivery system, patient selection and technique.

Cryogen

Maximum cell destruction is achieved by a rapid freeze, achieving temperatures of less than -40°C at the base of the lesion, a slow thaw and carrying out at least two freeze thaw cycles.² This can generally only be achieved by using liquid nitrogen which is the coldest (-196°C), most versatile, cheapest cryogen available. 

Over the counter cryogens such as home freezers like Wartner, which contain a mixture of dimethyl ether and propane (DMEP), are much less effective, as most only get down to -32°C at the surface of the wart with a very slow freeze. Hand held medical devices such as Histofreezer or Dermafreeze also contain DMEP and are equally ineffective and far too expensive per unit cost to make them practical in general practice. Nitrous oxide gas, while not as cold as liquid nitrogen, can reach -89°C and can give reasonably good results provided there is meticulous attention to technique. 

Liquid nitrogen cryosurgery via a closed hand held cryogun is the safest, most effective, most versatile method to deliver a freeze. Applying liquid nitrogen with cotton bud is not as affective but is still more effective than nitrous oxide gas or Histofreezer.

Patient selection

Patient selection is crucial in delivering effective cryosurgery. Children under the age of six do not make good candidates for cryosurgery for warts and doctors should resist parental pressure to freeze warts in this age group. The only exception is freezing molluscum contagiosum, which usually clear up with a tiny, almost painless, three second freeze. 

Children between the ages of six and 12 years are generally poor candidates for cryosurgery unless the child (not just the parent) is highly motivated, can understand what is involved and is very eager for treatment. I will not treat children with cryosurgery for warts greater than 4-5mm in diameter or a cluster of warts together, unless the child can tolerate local anaesthetic. 

Other poor candidates for cryosurgery are needle phobics and patients with immune suppression such as diabetes or transplant patients.

Technique

There is a limit to the depth of freeze one can achieve with cryosurgery. As you freeze from the surface down, the isobars get progressively warmer until equilibrium is reached between the cold of the cryogen at the surface and the heat of the skin from the underlying circulation. Hypertrophic warts are often covered with thick keratin, which acts as a thermal insulator. This has to be removed with a blade to allow the freeze to penetrate to the base of the wart. Even after removing keratin, many large warts can be 4-5mm deep. 

Success with cryosurgery is increased dramatically when a wart is debulked. Generally, this can only be achieved by applying local anaesthetic and surgically paring down the wart. For hand warts, I like to have them flush with the surrounding skin before beginning cryosurgery. For plantar warts, I usually pare them out leaving a crater to freeze into. In this way, I aim to remove 75-90% of the wart before starting the freeze. Another bonus is that the local anaesthetic makes the whole procedure far more tolerable for patients and more enjoyable for the doctor.

For most warts greater than 4-5mm in diameter or for a cluster of warts together, the discomfort of a prick with a 30 gauge needle with local anaesthetic is generally a lot less painful than trying to treat the wart using cryosurgery without local anaesthetic. 

Using this technique, I constantly get a success rate of over 90% with a single treatment for hand warts and verrucas³. Another advantage to debulking is that there is less necrotic tissue to die off post-cryosurgery. The only disadvantage is that there can be a lot of bleeding during and after the treatment. You have to be careful not to contaminate your cryogun with blood. I put on a fresh glove just before I pick up my cryogun for the freeze. Post-operative bleeding can usually be controlled with a pressure dressing and elevation. Post-operative pain can usually be controlled by giving paracetamol or ibuprofen immediately after the session of cryosurgery, before the local aesthetic has had time to wear off. Most warts will heal in three to six weeks.

Most bulky warts require two freeze-thaw cycles. There is some controversy, even among expert cryosurgeons, about what constitutes a freeze-thaw cycle. However, most now agree on the following definition:

Freeze-thaw cycle

• Start freezing as quickly as possible until the whole wart is frozen
• Continue freezing until a halo of normal uninfected skin, 1-2mm around the wart, is also frozen
• Continue to freeze (at a slower rate to avoid excessive lateral spread) for 10 seconds
• Then let the wart thaw out completely without heating, before starting a second freeze-thaw cycle in exactly the same way, if required.

Freezing down the auroscope cone is a useful technique for plantar warts, which allows you to get deep penetration of the freeze, without too much lateral spread. This leads to a higher success rate with lower morbidity, such as blisters. Spray down the auroscope cone with a C or E spray tip for 10 seconds only, as this is a much more concentrated form of cryosurgery than using the open spray technique. 

Flat warts (plain warts) are usually quite superficial and so are much easier to treat. They do not usually require paring or debulking because they are usually small and can often be treated without local anaesthetic. Ano-genital and mucous membrane warts are usually soft with no keratin and again do not usually require paring or debulking before cryosurgery. Amitop (tetracaine) topical anaesthetic works well and quickly (about 15 minutes) on mucous membranes.

Periungual warts usually occur as a result of damage to the cuticle, which is normally self inflicted from biting or picking.They can be difficult to manage, as the periungual skin is very delicate. I usually pare them down and freeze them gently with a five to seven second freeze and only one freeze-thaw cycle. 

Side effects

Pigmented changes (hypopigmentation or hyperpigmentation) can sometimes occur, particularly in dark skinned patients, but the pigment usually comes back after a few months, particularly when the freeze-thaw cycle is not more than 10 seconds. Nerve damage is very rare when treating warts. If it does occur, for instance on the digital nerve, it may result in a temporary numbness of the side of the finger that will resolve after a few months. 

Success rate

The maximum number of warts I would treat in any one session is approximately six to 10. The maximum number of times I would freeze any one wart is three different sessions. If they are not cleared after this, there is little point in persisting with cryosurgery. I would usually then revert to other techniques or perhaps try and encourage the patient to simply live with the wart and keep it under control by paring it at home, which makes it look and feel better.

References

1. Gaitanis G et al. Immunocryosurgery for basal cell carcinoma; results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application. J Eur Acad Dermatol Venerol 2009; 23:1427-1431 
2. Baust JG et al. The patho-physiology of thermoablation:optimizing cryoablation, Curr Opin Urol 2009; (19) 127-132
3. Buckley D. Cryosurgery treatment of plantar warts. Ir Med J 2000, 93(5): 140-143