Freeze-thaw-freeze Method for HPV Infection This method is more effective as compared to single-apply method. In this method, the application continues till 5 mm margin of skin or mucosa is frozen. When the skin turns white freezing continues for another 30 seconds and then the skin is ready to thaw. Since it is painful, patient’s pain tolerance must be considered. If the patient can tolerate the pain, second cycle is applied. After 24 hours of the treatment a bulla forms over the thawed region. If necessary, another course of treatment is applied for 1-2 weeks.