Therapy for oral verrucous carcinoma (VC) is challenging because recurrences are common, and potential anaplastic transformation after radiation therapy may be a concern. The most prevalent treatment in the United States for verrucous carcinoma is surgery alone (69.7%), followed by surgery combined with irradiation (11%), and irradiation alone (10.3%).  Irradiation may be more common in advanced cases than in early cases (see Surgical Care).
Surgical treatments are probably best (see Surgical Care below), and radiation therapy is generally considered a last resort. In oral verrucous carcinomas, irradiation is reported to produce highly malignant behavior with metastases, but some still use this treatment with confidence. [23, 55, 58, 59] In one study, none of the 16 patients with verrucous carcinomas had features of anaplastic transformation after radiation.  Many believe that radiation is an excellent choice for small and large oral and other types of verrucous carcinomas, with results comparable to surgery. [2, 11, 23, 55, 58]
Combined radiochemotherapy with vinblastine, methotrexate, and bleomycin is effective in the treatment of verrucous carcinoma of the head and neck.  It could be successfully used with inoperable verrucous carcinoma or as an alternative to surgery.
The possibility of anaplastic transformation due to radiation must be considered,  although this complication is rare. A risk factor of 10.7% is reported for anaplastic transformation of verrucous carcinoma after radiation therapy.  Caution is advised in the irradiation of an Ackerman tumor, except in advanced tumors for which surgical resection and other modalities are not feasible.
In one study, 17 cases were described. In 7 cases with oral verrucous carcinoma and 1 case with verrucous carcinoma of the nasal cavity, one of several modalities of radiation therapy was the initial treatment. Despite regression of the verrucous carcinoma with irradiation, a rapid anaplastic transformation (as seen at histologic examination) with a corresponding aggressive clinical tumor behavior developed in 3 patients, with an onset at 2, 5, and 8 months after therapy. The ionizing radiation may have produced this lethal clinical outcome. Among 4 patients who underwent irradiation for oral verrucous carcinoma, anaplastic transformation developed in 1 patient, with onset at 3.5 months after treatment. 
In the studies by Perez et al  and Fonts et al,  an excellent immediate response to irradiation was followed by transformation, which was usually heralded by rapid tumor growth. Patients with similar results were described later. [62, 63, 64, 65, 66] These patients included a man with oral verrucous carcinoma who was treated with a 6-MeV linear accelerator and who developed an undifferentiated squamous cell carcinoma in the cells of the verrucous carcinoma. 
In another series of 10 patients with laryngeal verrucous carcinoma, 3 were treated with radiation. Anaplastic transformation occurred in 1 patient, who died from dissemination 10 months later. 
Patients in some of these studies had large or extensive verrucous carcinomas and seem reminiscent of those Goethals et al  examined in a series of 55 cases of verrucous carcinomas of the oral cavity. Three of these patients apparently died from distinct more-undifferentiated lesions that metastasized. Other cases of malignant transformation have been noted. [53, 55, 58]
Proton radiation therapy may induce complete regression in oral verrucous carcinoma. 
Photodynamic therapy using a topical application of 20% 5-aminolevulinic acid followed by multiple 3-min fractionated irradiations with a light-emitting diode (LED) red light may be an effective and successful treatment modality for oral verrucous carcinoma.  Photodynamic therapy with systemic administration of the photosensitizer Photocarcinorin may be effective in the treatment of oral florid papillomatosis.  It can be used once a month for numerous months and may represent a good option for elderly patients.
Bleomycin iontophoretic therapy may be beneficial for lip verrucous carcinoma.  Intra-arterial bleomycin  and oral methotrexate  may be used to treat oral verrucous carcinoma. Intra-arterial methotrexate infusion may be effective as a primary therapy for oral verrucous carcinoma. 
If HPV is determined to be an etiologic agent, the development of a subunit vaccine directed against viral oncoproteins may be a further long-term goal. 
The most prevalent treatment in the United States is surgery alone (69.7%), followed by surgery combined with irradiation (11.0%) and irradiation alone (10.3%).  For oral cavity verrucous carcinomas, surgery alone is more common among early cases (85.8%) than among advanced cases (56.9%), and a larger proportion of patients with advanced disease receive irradiation alone or surgery and irradiation combined. Most laryngeal verrucous carcinomas are treated with surgery (60.3% for early disease, 55.6% for advanced disease). Compared with verrucous carcinomas in the oral cavity, laryngeal verrucous carcinomas are more often treated with radiation alone or surgery combined with radiation.
The best approach to oroaerodigestive verrucous carcinomas is probably tumor destruction combined with careful and frequent follow-up evaluations to assess for recurrence as well as separate new (and higher-grade) squamous cell carcinomas of the aerodigestive tract.
Surgery either by means of traditional excision or a Mohs micrographically controlled excision is a popular option. The latter is a good approach in select patients. [75, 76] Surgical diathermy, or electrocautery with thorough electrocoagulation of the tumor bed and the surrounding regions of leukoplakia or other abnormalities, is another surgical modality.  Radiation therapy has been used with surgery.  A combination of surgical excision and chemotherapy has certain advantages in oral verrucous carcinoma. 
Verrucous carcinoma is a locally aggressive and destructive tumor that advances into adjacent bone and other structures. Regional lymph node metastases occasionally occur, but distant metastases are rare. Rapid anaplastic transformation with widespread metastases has been described in a few patients with oral verrucous carcinoma. This complication mainly occurs after radiation therapy.
Patients with verrucous carcinoma (VC) should be carefully monitored because the following might develop:
Aggressive squamous cell carcinoma
Anaplastic transformation of a preexistent verrucous carcinoma