Intralesional Immunotherapy - A New Method to Treat Stubborn Warts

Doctors have recently started trying a new method to treat these stubborn warts: injecting the HPV vaccine directly into the warts. This method is called intralesional immunotherapy. It's different from the usual way of giving the vaccine as a shot in the muscle, which is meant to prevent HPV infections.

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Treatment for Cutaneous Warts

Cutaneous warts, caused by the human papillomavirus (HPV), are a common and often persistent dermatological problem. Traditional treatments include cryotherapy, electrodesiccation and curettage, topical salicylic acid, imiquimod, 5-fluorouracil, and cantharidin. Less frequently, treatments like immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester, topical/intralesional cidofovir, oral retinoids, and intralesional bleomycin are used. CO2 or pulsed dye lasers, photodynamic therapy, or local hyperthermia can benefit persistent cases. Despite the variety of treatments available, managing recalcitrant warts remains challenging.

The Role of Intralesional Immunotherapy

Intralesional immunotherapy has been explored using agents such as candida antigen, mumps antigen, combined measles, mumps, and rubella (MMR) vaccine, tuberculin purified protein derivative, and bacille Calmette-Guerin vaccine. This approach aims to stimulate a local immune response directly at the wart site, enhancing the body's ability to fight the virus.

Intralesional HPV Vaccine: A New Approach

The intralesional use of the HPV vaccine has shown significant promise. Recent studies have focused on the clinical effectiveness and safety profile of intralesional administration of the 9-valent HPV vaccine for treating recalcitrant warts.

The 9-valent HPV vaccine covers HPV subtypes 6, 11, 16, 18, 31, 33, 45, 52, and 58 and has demonstrated a good response, with complete clearance in 60% of cases and no evidence of recurrence.

Mechanism and Benefits

HPV vaccines contain noninfectious HPV-like particles made from the L1 capsid protein of each HPV subtype. The homology between the L1 capsid proteins of the HPV subtypes responsible for common warts (HPV types 1-4) and those found in the vaccines suggests that cross-immunity may help elicit an immune response against a wide range of HPV subtypes.

The systemic administration of 2-valent and 4-valent HPV vaccines has shown promise in treating common warts. Recently, three case reports documented the routine systemic administration of the 9-valent HPV vaccine, which cleared all existing warts completely.

Comparative studies have found that intralesional injection of HPV vaccines is more beneficial than routine intramuscular administration. For instance, Nofal et al. reported an 81.8% complete clearance rate in patients treated with the intralesional 2-valent HPV vaccine, compared to 63.3% in those receiving the vaccine intramuscularly. These findings suggest that intralesional administration may provide a higher local concentration of the vaccine, enhancing its therapeutic effect.

Immune Response and Long-Term Efficacy

The intralesional HPV vaccine induces a robust cell-mediated immune response. By injecting the vaccine directly into the wart, Th1 cytokines such as interleukin 2 and interferon-gamma are increased, activating cytotoxic and natural killer cells. This response helps eradicate the HPV infection at both injected and noninjected sites. The trauma of the injection itself may also contribute to the immune response.

The long-term immunity induced by HPV vaccines likely explains the lack of recurrences observed in studies. For example, no recurrences were recorded in the present study, or the study by Nofal et al., and only one recurrence was noted in another study using intramuscular vaccination.

Safety and Limitations

The primary adverse effect observed with intralesional HPV vaccine administration was transient localized pain at the injection site. No systemic adverse effects were reported. However, the small number of participants and the retrospective nature of some studies highlight the need for more extensive, prospective, double-blind, placebo-controlled studies.

Conclusion

Given its safety profile, accessibility, and relatively low cost, the intralesional 9-valent HPV vaccine should be considered a potential therapeutic option for treating recalcitrant cutaneous warts. Further research is needed to establish the optimal treatment regimen and confirm the therapeutic value of this approach.

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