**4. Treatment**

Warts are usually self-limiting. Large studies have shown complete spontaneous remission in 42% of patients after 2 months; in 53%, after 6 months; and in 65%, after 2 years [2]. The intact immune system plays the most important role for preventing HPV infection. This can be seen in patients with primary immunodeficiency or in immunosuppressed patients.

HPV-induced warts are the most common skin disorder in organ transplant recipients [3]. Children with recalcitrant extragenital wart may suffer from primary immunodeficiency. It has been shown that immunosuppressed patients experience resolution of treatment-refractory warts once their immune status has improved [4]. The known spontaneous remission of HPV-induced warts, which is attributed to cellbound mechanisms, underscores the role of the immune system, including an increase in Th1 cytokines and infiltration of T cells (CD4+ , CD8+ ) around the diseased tissue [5].

Guidelines for the management of cutaneous warts have been prepared for dermatologists on behalf of the British Association of Dermatologists [6]. The guideline highlighted the ideal aims of treatment of warts as follows: (i) Removal of wart without recurrence. (ii) Treatment should result with no scars. (iii) Immunity that induced by treatment should be lifelong [5]. The general principles observed in the treatment of warts are the following: (1) There is no need to treat all warts. (2) Treatment indications are pain, interference with function, cosmetic embarrassment and risk of malignancy. (3) All the treatments have success rate not very high (average 60 ± 70% clearance in 3 months). (4) An immune response is usually essential for clearance. Immunocompromised individuals may never show wart clearance. (5) Younger individuals with short duration of illness usually have the highest clearance rates for various treatments [5].

There is a high rate of spontaneous remission, especially in children, so 'wait-andsee' approach is feasible in many cases. Regular filing or paring down the hyperkeratotic layer makes the lesion thin and comfortable. Simple measure to limit the spread of lesion should be encouraged. The treatment of warts can be broadly classified into destructive, antimitotic, virucidal, immunotherapy, and some folk and alternative therapies which have recently become popular again.

The goals of wart treatment are to resolve all or a maximum number of warts, make it painless, need only one or a part of a wart treated, only need minimum number of treatments, leave no scar, offer lifetime HPV immunity and be easily available for all patients [7]. The criteria for wart treatment, developed by the American Academy of Dermatology in 1995, [7] include (1) the patient's desire for therapy; (2) symptoms of pain, bleeding, itching or burning; (3) disabling or disfiguring lesions; (4) large numbers or large sizes of lesions; (5) the patient's desire to prevent the spread of warts to unblemished skin of self or others; and (6) an immunocompromised condition [6].

### **4.1 Destructive therapy**

The lesions are damaged or removed by different procedures followed by clinical cure. The destructive therapies include surgical removal by curettage and cautery, chemical cautery, cantharidin, cryotherapy, electrocautery, radiocautery ablation, infrared coagulation, photodynamic therapy, and lasers.

### *4.1.1 Surgery*

Curettage followed by cautery was an early and still widely practiced method of surgical removal of warts. A success rate of 65–85% has been reported in surgical

therapy, but scarring and recurrence rate are high (30%), and the sole of the foot is the site where scarring is particularly problematic. Curettage followed by cautery is most commonly used for filiform warts on the limbs and face [8]. Excision is usually to be avoided as scarring is inevitable, and there is frequent chance of recurrence in the scar.

### **4.2 Salicylic acid**

It is keratolytic, reduces the thickness of warts and may also stimulate an inflammatory response. Over-the-counter preparations are available as 17% salicylic acid combined in a base of flexible collodion or as a 40% salicylic acid plaster patch [9]. It is minimally expensive, convenient and reasonably effective, with negligible pain, but results require weeks to months of treatment. Occasionally, contact dermatitis due to colophony may develop, and to avoid systemic toxicity, it should be applied only in limited area. Treatment result with salicylic acid therapy extremely depends on patient compliance. Before pairing or debridement of the dead, hyperkeratotic tissue, wart(s) should be soaked in warm water for 5 min. The salicylic acid preparation should then be applied to the debrided wart [10].

### **4.3 Chemical cautery**

Strong chemicals can destroy tissue. Trichloroacetic acid (**TCA**) and bichloroacetic acid (**BCA**) are not readily absorbed by tissue; it kills warts by denaturing and destroying the proteins in the cells. Treatment via **chemical cautery** with a solution of 60–90% trichloroacetic acid (TCA) is most effective when treating few small, moist lesions. There is a complete clearance of warts in 70% of patients who received up to 6 treatments of trichloroacetic acid. Thirty percent of patients who were treated with trichloroacetic acid developed ulcerations at the site of its application [11]. Recurrence rate is not clear. Silver nitrate is probably most widely recognised in its historical use to prevent conjunctivitis in newborns [12]. This treatment for warts is currently more widely used in the United Kingdom where non-prescription 95% silver nitrate caustic applicator pencils are available [13]. Chances of excessive burn and pigmentation are there.

### **4.4 Cantharidin**

A terpenoid secreted by blister beetles, which is absorbed by lipids in keratinocytes, activates serine proteases and leads to acantholysis [14, 15]. Depending on the amount, concentration, duration of exposure and occlusion, an intraepidermal blister will form and resolve, within a week [16]. The superficial nature of the injury reduces the risk of scarring. One randomised control trial shows that cantharidin is effective, is safe, yields better cosmesis and requires fewer applications than TCA for the treatment of warts when used sufficiently far from mucosal and intertriginous areas. It was also shown to be well tolerated and that patients being treated with Cantharone were significantly more satisfied than those treated with TCA. This may be attributed to less pain during application and during the entire treatment, better cosmetic results and perhaps fewer visits [17].

### **4.5 Phenol (carbolic acid)**

It is a strong caustic agent that can penetrate deep into tissue, produces chemical burn with escher and is not used routinely for treatment of common wart.

**35**

*4.8.2 Liquid nitrogen therapy*

*Human Papillomavirus Infection: Management and Treatment*

Strong (80%) phenol solution for the treatment of common warts showed that phenol was an effective form of treatment for warts. It must be used by a physician

Topical tretinoin, although currently recommended for the treatment of acne,

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid has a good curative effect, especially in recalcitrant facial flat warts [20–22]. It is unclear, but selective photothermolysis of oxyhaemoglobin within the dilated microvasculature of the warts leads to destruction of capillaries followed by improvement of warts, may be the mechanism of action of this curative effect [23]. Many factors affect the efficacy of PDT, including photosensitizer concentration; solvent type; incubation time; type, dose, and time of irradiation of the light; and the area of exposed parts. ALA gel (10%) was applied topically to lesions and incubated for 3 h. The lesions were irradiated by an LED light of 630 ± 10 nm at dose levels of 60–100 mW/cm**.** At the 24-week follow-up, the average effective rate was 88.8%, with no recurrences.

Cryotherapy induces cold thermal injury in the lesion. Cryotherapy may have an effect on wart clearance either by simple necrotic destruction of HPV-infected keratinocytes or possibly by inducing local inflammation conducive to the development of an effective cell-mediated response [25]. Dimethyl ether spray, carbon dioxide snow and liquid nitrogen all produce cold thermal damage to the skin. Different types of devices and techniques are used to induce targeted cold injury to

It is in aerosol form, easy to handle and stored in normal room temperature, and its preservation time is very high (nearly 3 years), available in market and easy to buy. As the evaporation temperature reaches −57°, therefore, it is likely to be less effective, and efficacy in inducing tissue temperatures adequate for cell necrosis appears low [26]. But one multicentre RCT on comparing effects of DMEP and LN2 shows that no clinically relevant differences between the efficacy, tolerance and safety of the two cryogenic agents used in primary care were found. The low freez-

Having a temperature of −196°C, the coldest freeze, is the most commonly used method in medical practice. It is very effective in elimination of a large

warts. Carbon dioxide slush (−79°C) is now less commonly used.

ing of DMEP was sufficient for the cryotherapy of benign lesions [27].

*4.8.1 Mixture of dimethyl ether and propane (DMEP)*

has also been reported to be of benefit in plane warts. A study of 25 children with plane warts treated with 0.05% topical tretinoin cream (applied once daily for 6 weeks) was compared with a control group of 25 untreated children. After 12 weeks, clearance of warts was observed in 84.6% of the treated group as compared with 32% of the control group. It was well tolerated with some redness and

*DOI: http://dx.doi.org/10.5772/intechopen.92397*

**4.6 Retinoic acid**

and should not be used in extensive areas [18].

peeling in 42.3% of the treated group [19].

No significant side effects were reported [24].

**4.7 Photodynamic therapy**

**4.8 Cryotherapy**

Strong (80%) phenol solution for the treatment of common warts showed that phenol was an effective form of treatment for warts. It must be used by a physician and should not be used in extensive areas [18].
