Warts are benign skin and mucous membrane growths due to the human papillomavirus (HPV), which exists in more than 100 subtypes. HPV can be found in any part of the body and there are formations such as skin warts, genital warts, flat warts, deep warts on palms and soles known as Myrmecia, focal epithelial hyperplasia, Epidermodysplasia verruciformis, plantar cysts and others. Warts can be transmitted through direct or indirect contact and instances where the skin barrier is compromised and increases the chances of developing warts. Some of the HPV types include 6, 11, 16, 18, 31, and 35, are associated with cancers especially in case of in persons with genital warts or immunocompromised persons. Also, HPV types such as 5, 8, 20, and 47 fall under the oncogenic group that causes epidermodysplasia verruciformis. 

• Frequency: Common warts are widespread around the world and affect approximately 10% of the general population. Among school-aged children, they are present with frequencies of 10 to 20%.
• Age: However, these are not restricted to any age of life since they can grow at any stage of life. It is rare in infants and very young children, but the cases are prevalent when children join school and the number increases between 12 and 16 years of age.
• Race: Although there are no significant differences in the incidence of warts between males and females, warts occur approximately twice as frequently in Caucasians as in Blacks or Asians. For instance, focal epithelial hyperplasia, also called Heck disease, occurs more frequently among Native American people.
• Sex: There is a balance of the occurrence of this skin condition between males and females.

Of the 100 HPV subtypes, some of them are considered high-risk HPV as they are associated with cancerous cells. These include types 6, 11, 16, 18, 31, and 35, of which the ones that transform more malignantly are those associated with genital warts and immunocompromised persons. However, HPV types 5, 8, 20, and 47 may also lead to malignancy in cases of epidermodysplasia verruciformis. 

Although most warts are usually benign, there have been instances where the disease has advanced to verrucous carcinoma. This type of carcinoma is a malignant neoplasm, very slow growing and well-differentiated squamous cell cancer that resemble a verruca vulgaris. It may occur at any site on the body but is more commonly found in the plantar region.  

HPV has over 100 types and of them only a few results in the formation of skin warts at certain body regions. However, HPV tends to move around the different parts of the body through skin. It regularly results in genital warts, flat warts and palmoplantar warts. It spreads through direct or indirect touch due to skin to skin contact especially when the outer skin barrier has been broken. In most instances, HPV affects only the epithelial layers of the skin; therefore, systemic spread is highly rare. Virus targets the upper epithelial layers, but it has been observed that viral particles may also reside in the basal layer. 

Specific HPV types are associated with different types of warts: 

Common warts: Types 2 and 4 were most common, then types 1, 3, 27, 29, and 57. 

Flat warts: Types 3, 10 and 28. 

Deep palmoplantar warts: Type 1 was most frequently observed, with types 2, 3, 4, 27, and 57 also present. 

Cystic warts: Type 60. 

Focal epithelial hyperplasia: Types 13 and 32. 

Butcher’s warts: Type 7. 

About 66% of warts are known to naturally disappear gradually within the duration of 2 to 3 years, thus making it difficult to determine the efficacy of therapies. Warts that tend to resolve independently are not likely to have residual effects, such as scarring. On the other hand, most of the topical treatments for warts can cause moderate to severe skin scarring. Also, the number of patients who fail to respond to treatment is high, causing pain and severe scarring.  

Age group 

Warts in children and teenagers within the age group of 12 to 16 years are particularly at risk of developing warts and these include plantar warts, flat warts, and common warts. Warts can also develop in adults; they can develop genital warts, or they may develop warts in certain workplaces. Even elderly people develop warts, though they might not as frequently as they used to since HPV exposure is limited and immune responses change. 

• Plantar warts 
• Flat warts 
• Genital warts 
• Focal Epithelial Hyperplasia  

• Immunocompromised individuals 
• Occupational Exposure 
• Eczema 

Acute Onset: Common warts usually appear over time and can take anywhere between weeks and months to fully manifest. It is not usually found, but the warts may begin to stand out, or cause symptoms such as pain, burning or itching if it becomes irritated or infected. 

Chronic: Generally, warts may take several months to even years before they are imprecated without treatment. The changes can be inconspicuous and slow, in some cases the warts may increase in size or numbers. 

Initial Management: Since approximately 60% of warts regress on their own within 24 months, observation is sometimes recommended. This approach reduces the likelihood of a patient receiving treatment when the problem may clear up on its own. However, there are several complications which include chances of developing bigger warts or having them spread on the skin. 

First-Line Treatments: 

Topical Agents: 

• Salicylic Acid: This product is usually selected initially because of the low-price range and the possibility of its application at home. It has an estimated cure rate ranging from 50% to 70%. 
• Tretinoin: A substance related to vitamin A that has been used with some efficacy for flat warts. 
• Podophyllin and Topical 5-Fluorouracil: Used specifically in the treatment of conditions, usually masked.

Second-Line Treatments: 

• Cryotherapy: Freezing and/or destruction of the wart using liquid nitrogen, usually done in a clinic or other health facility.
  Imiquimod: Imiquimod is an immune response modifier that is administered for the treatment of genital warts and of other forms as well.
• Retinoic Acid: Which is applied in specific types of warts like the flat warts.Advanced and Recurrent Cases: 
• Cidofovir: A capsule systemic antiviral for recalcitrant warts; originally used for CMV in AIDS patient. 

Intralesional Injections: 

• Immunotherapy (e.g., Candida): Activates the body’s natural defenses against the wart. 
• Bleomycin and Interferon Alfa: It is applied on hard to remove warts. 

Surgical Treatments: 

• Electrodesiccation: The method electrofuges and by applying electric current, it burns the wart tissue. 
• Laser Therapy: Performs the purpose of wart removal using a laser light.
  Excision: Excision of the wart, which is mostly done for large or recurrent warts that have not been controlled by other means. 

Systemic Treatments: 

• Cimetidine: An oral medication for which scientific evidence to support its efficiency is very scarce. 

Dermatology, General

• Adhesiotherapy: Applied and maintained by covering the affected area with duct tape for six days and then, removed and scraped with fine surface. It is thought that this method starves the wart and at the same time invokes the immune system of a person. 
• Over-the-Counter Freezing Kits: It is a home treatment for warts that will cryotherapy but not as strong due to the freezing agent applied on the kits. It is only advisable to use them in the skin’s treatment since they can harm healthy skin in close contact with the affected skin. 
• Cryotherapy: Another approach that can be administered by a healthcare provider is by using liquid nitrogen treatment where the wart is frozen and later will drop off. Although it is still within the spectrum of the medical approach, it is not invasive in terms of treatment procedures. 
• Hypnosis: It applies the technique of relaxation to eliminate other causes or stress or psychological conditions that would normally result in warts taking longer to disappear. There is very little clinical evidence to be found supporting its effectiveness and this information is mostly given by word of mouth. 

• Salicylic Acid: This product comes in liquid form, gel, pad or ointment. Wash the affected area with warm water for 5-10 minutes then apply it directly on the warts four times daily. The treated area can be covered by a bandage after the treatment. This therapy should be administered for several weeks up to months. The cure rates are established at between 50% and 70%. 
• Imiquimod: It is available as a cream that reduces the probability of those who take fertilizers developing allergy to them. This medicine should be applied on the wart three times a week before going to bed and kept on for 6 to 10 hours then washed off with soap and water. Treatment is usually carried out for up to 16 weeks. It is useful for genital warts, plantar and some skin warts because it enhances the immunologic response at the site of application. 
• Podophyllin and Podofilox: It comes in the form of a Solution or as a gel. Podophyllin is prescribed by a health care provider in the clinic while Podofilox is self-administered by the patient at home, by applying it twice daily in the morning and in the evening for three consecutive days and then leaving it off for four consecutive days. This process is carried out for up to a four-week cycle. 
• 5-Fluorouracil: In its topical formulation, it is available as a cream. Directly applied to the wart and sealed with a plaster or adhesive bandage usually for several weeks. Some warts may be resistant to the initial treatment and this form or treatment is considered appropriate. 
• Tretinoin: Used topically, on the affected area of the wart usually at night before going to bed. It is used in flat warts and continued for several weeks to months.  It is most useful in flat wart conditions, which are usually induced by human papilloma virus. 

Dermatology, General

• Liquid Nitrogen: It is administered employing cryospray, cotton-tipped applicators, or a cryoprobe. The wart is then covered with liquid nitrogen, making it to freeze and in the process forming a blister. The treatment is often conducted progressively at intervals of 1-3 weeks for several sessions. The lesion clearance rate is high for common warts, but their cure may take several treatments. 

Dermatology, General

• Bleomycin: It is an antineoplastic antibiotic that is effective for the inhibition of DNA formation thus causing cell death. An example is when it is administered subcutaneously, it results in necrosis of the wart tissue within the area. Usually administered intralesional to the wart by a health care professional, often with an interval of 2-4weeks. It is suggested for resistant warts, and it gives clearance rates that range from 60% to 90%.  
• Candida Antigen (Immunotherapy): It works locally by causing an immune response to the wart as a foreign body. The immune system recognizes the injected antigen and responds to it in a manner that would also eliminate the wart tissues. It is administered intralesional into the wart, commonly with a separation of 3 to 4 weeks between each session. 
• Interferon Alfa: It is an antiviral drug that helps to boost the body immune response to viruses. It works through stimulating the manufacture of antiviral proteins and increasing the vigilance of immune cells. It is applied topically to the surface of the wart, and often it is used at interval of 1 to 3 times a week for several weeks. 
• 5-Fluorouracil (5-FU): It is anticancer chemotherapeutic agent that acts by preventing DNA synthesis and cell division. When injected into the wart, it interferes with the formation of new skin cells in the wart area. Intralesional injections are commonly administered by a physician and can be administered in conjunction with other treatments to remove lesions such as salicylic acid or cryotherapy. 

Dermatology, General

• Cimetidine: A highly available H2 receptor antagonist employed in the treatment of gastric ulcers more often. It has been believed to increase cell mediated immunity which of helps in the clearance of warts. In the form of oral tablets, these medications are normally administered at 20 to 40 mg/kg/day in three divided doses. 
• Cidofovir: It is an antiviral drug of the SAH class that incorporate into the newly synthesized viral DNA. Off label it is used in warts but its major use is in immunocompromised patients with cytomegalovirus (CMV) infections. This may either be administered intravenously or a topical cream or ointment for use in the affected area. 

Dermatology, General

• Cryotherapy: Involves the use of extremely low temperatures, often in the form of liquid nitrogen, to freeze and eliminate wart tissues. This results in the development of a blister raising the wart above the skin surface. 
• Procedure: Application of liquid nitrogen is done through cryospray, cotton swab and cryoprobe to the affected area with the wart. Each application takes 10 to 20 seconds, and the procedure needs to be repeated 1 to 3 weeks until the wart disappears. 
• Laser Therapy: A type of light energy that directs heat on the wart and destroys the wart tissues. Different kinds of lasers can be applied, exemplified by the pulsed dye lasers, CO2 lasers as well as the Nd laser. 
• Procedure: The laser is pointed at the wart, and this heats up the tissue in the wart and causes its destruction. It is possible to apply local anesthesia to reduce pain. 

Dermatology, General

Wart management is a stepwise process which depends on the signs and symptoms, the patient himself or herself and the response to the treatment.  

First, an attempt is made to classify the wart based on its type and site and to evaluate the patient’s characteristics, such as age and immune system, as 60% of warts disappear within two years without treatment. Initial interventions involve the use of topical medications such as salicylic acid, which forms the basis of most first-line treatments for warts, and cryotherapy in which the wart is exposed to the effect of liquid nitrogen.  

The second line treatment for the hard to remove, unreceptive warts include the invasive methods like laser therapy, electrosurgery, and intralesional bleomycin or candida antigen injections. Benzodiazepines are used for generalized or long-standing manifestations; cimetidine, isotretinoin or cidofovir are regarded as advanced and systemic procedures combined with immunomodulating preparations to enhance the immune functions. Adhesive treatment, hypnosis, and hyperthermia, as well as the use of propolis and plant extracts are also used as non-drug options for managing symptoms.