Human papillomavirus (“HPV”) is a group of viruses that is extremely common worldwide. HPV infection can cause normal cells to turn abnormal. Different types of HPV have different effects. For some “high-risk” HPV types, this change can lead to malignancy in the host. However, out of the more than 150 HPV types, only 13 are known to be cancer causing. The other “low-risk” HPV types lead to skin warts. Some HPV types, such as 6 and 11, have a tendency to target anal and genital areas, while others target the skin in other parts of the body.
Non-genital cutaneous warts are extremely common, especially in children. There are three main types of non-genital warts: common warts (verruca vulgaris), plantar warts (verruca plantaris), and flat warts (verruca plana). Common warts typically present on the fingers and hands and comprise up to 70% of cutaneous warts. Alternatively, plantar warts occur on the soles or toes of the foot, while flat warts may be present on the face or hands.
Common warts are typically associated with HPV types 2 and 4, plantar warts with type 1, and flat warts with types 3, 10, and 28. All of these HPV types carry low malignant potential. Transmission occurs through direct skin contact, and the incubation period is typically between two to six months.
Reliable data regarding incidence and prevalence of non-genital warts is difficult to ascertain. It is hypothesized that up to 20% of children have cutaneous warts, while prevalence in adults is roughly 3.5%. Peak incidence is thought to occur in children ages 12 to 16. Individuals who are immunocompromised, have eczema, or handle meat for a living are also at a greater risk of developing cutaneous warts.
Standard of Care
Visual examination is used for diagnosis. In rare cases, scraping or shave biopsy may be used. It is important to note that within two years, two-thirds of children will experience spontaneous clearance of their warts. Spontaneous remission may also be achieved in adults, albeit at a slower rate. Although intervention is not necessary for cutaneous warts, treatment may be desired due to functional impairment, pain, or cosmetic concerns.
Typical treatment regimens for common and plantar warts include topical application of salicylic acid and cryotherapy either alone or in combination. Salicyclic acid exfoliates the skin to remove the infected lesion, while cryotherapy freezes the lesion off with liquid nitrogen. In some cases, other treatments such as imiquimod, 80% trichloroacetic acid, or 5-fluoruracil may be initiated.
As seen in anogenital warts, current first-line treatments for cutaneous warts have serious limitations. First, the efficacy of both salicylic acid and cryotherapy is controversial, with reported cure rates ranging from no difference from placebo to near-complete clearance. Second, either therapy is inconvenient for the patient, requiring daily application of salicylic acid or bi-monthly cryotherapy procedures until the wart resolves. Moreover, the side effects of cryotherapy greatly limit its use. The frequency of procedure-associated pain generally restricts the treatable population to older children and young adults, and potential hypopigmentation of the treatment site rules out its use for facial flat warts.
Taken together, current treatments are often ineffective, inconvenient, and costly. HPV vaccination does not currently cover the predominant strains implicated in cutaneous warts. The widespread prevalence of cutaneous warts creates a large market opportunity for accessible and cost-effective treatment. As with anogenital warts, targeting the underlying HPV infection could potentially cure the condition, prevent recurrence, and benefit the large population lacking HPV vaccination coverage.