Eggert Stockfleth, MD & George Martin, MD
Viral Skin Carcinogenesis – Eggert Stockfleth, MD
Dr Stockfleth reviewed the latest data and the role of the human papillomavirus (HPV) in skin cancer. SCC is prevalent on 80% of sun-exposed areas in cutaneous SCC and the main risk factor is UV radiation (UVA and UVB). There are multiple risk factors during skin carcinogenesis. With a functional immune system, your body can repair DNA image or lead to programmed cell death, i.e, apoptosis.
What about cellular networks? Researchers are looking to identify the “guardian genes”. We have found that HPV 23 and 38 are the most prevalent types of virus and play a role in development of skin cancer. These HPV subtypes (23 and 38) induced anti-apoptotic effects in UV-damaged cells through the expression of two oncogenic proteins E6 and E7 which lead to persistence and accumulation of further mutations. Research is still ongoing regarding vaccination and treatment.
Actinic Keratoses – George Martin, MD
Unfortunately, field therapy for the treatment of AKs continues to remain underutilized in clinical practice even though we have a number of therapies available. Recent studies on dermatologist treatment practices demonstrate that 92% of patients treated for actinic damage are treated with cryotherapy alone; 7% with cryotherapy plus a prescription for a field therapy; and 1% of patients leave the office with a prescription for a field therapy alone. Why is field therapy underutilized? This is, in part, due to prolonged downtime, patient compliance issues, the costs of medication, and patient discomfort during therapy. Therapies such as ingenol mebutate and short duration 0.5% 5-FU and combination therapies have been developed to address the above noted issues.
Our expert panel (George Martin, Eggert Stockfleth, Ted Rosen, Neal Bhatia, Neil Swanson, and Marc Brown) reviewed various challenging clinical cases with AKs. Some of the recommendations and comments are as follows:
How does a dermatologist optimally treat AKs? For facial AKs, 5-FU remains the basis of field therapy in most clinical practices. During phase III clinical trials, clearance rates in excess of 70% were measured 30 days following daily treatment for 1 week using 0.5% 5-FU. Lengthening the therapy to 4 weeks results in better efficacy but is in Dr. Martin’s opinion not worth the additional downtime and patient local skin reactions. Dr. Martin protocol involves treating daily for seven days, then the patient has a rest period of 1 month, then he treats again for 2 weeks or longer depending on the desired clinical result. What about 3.75 imiquimod? The 2 week on-off-on for facial AKs results in significant downtime. Investigator initiated studies are looking at using 3.75% imiquimod daily for 7 days followed by a 2 weeks rest and then instituting once weekly applications. Ingenol Mebutate has also proven to be efficacious as a full-face field therapy using a single tube application to cover the entire face. Complete healing with excellent clinical responses have been observed in larger area therapies. Large controlled studies quantitating efficacy have not been completed.
Actinic damage on the chest of women poses a great challenge to the practitioner. Because of permanent depigmentation, imiquimod 3.75% should be avoided. While PDT has shown to be effective, it is off-label for use on the chest and does not have any well-controlled studies to support its use. Both ingenol mebutate and 5-FU are viable options for treatment of AKs on the chest. Ingenol mebutate 0.05% QD x 2 days results in a “chemical peel” like reaction but produces excellent AK clearance and cosmesis.
What about the management of a patient with significant AK damage on the dorsal hands and forearms? Combined use of 5-FU QD in the morning for seven days with 5% imiquimod QD in the evening for six days followed by three to four weeks of “rest” and repeating the cycle for a total of three cycles has proven effective. Using 0.5% 5-FU QD for ten days followed by ALA PDT (3 hour incubation) is also effective but painful. Ingenol mebutate .05% applied QD for two days, while approved by the FDA for treatment of the hands/forearms, lacks significant efficacy and might benefit from a three to four day regimen. To date there are no published studies looking at a longer treatment regimens for this area. It is important to remember actinic damage is a chronic disease which requires vigilance and therapeutic intervention.