Skin cancers are the most common malignancy in the United States and worldwide. Between 1994 and 2014, the diagnosis and treatment of melanoma and nonmelanoma skin cancers in the United States increased by 77%.1 The cost of treating melanoma and nonmelanoma skin cancers to the health-care system alone is estimated at more than $8 billion per year.2 The most common type of treatment for nonmelanoma skin cancers is surgical excision.
A recent single-institution case series study by Canadian researchers evaluated the use of hydrogen peroxide (33% H2O2) as a neoadjuvant treatment in the surgical excision of nonmelanoma skin cancers.3 The ASCO Post spoke with lead author Neil Mundi, MD, about the study results.
Neil Mundi, MD
Current Work
Please tell us a bit about your position and current work.
I am a head and neck oncologic and microvascular reconstructive surgery fellow at Mount Sinai Hospital in New York. My current research interest centers on the genetic landscape of head and neck cancers as well as the improvement of functional outcomes for patients who undergo reconstructive surgery. I’m also very interested in the management of skin cancers.
Novel Study
While you were at the University of Western Ontario in Canada, you were the lead author on a study looking at the use of 33% hydrogen peroxide as a neoadjuvant treatment prior to the surgical excision of nonmelanoma skin cancers. What initiated the interest in this novel approach?
For one, our group had come across papers describing the use of high-concentration hydrogen peroxide in the treatment of seborrheic keratoses and actinic keratoses. In addition, we’d seen papers on injected high-dose hydrogen peroxide as a radiosensitizer in the treatment of malignant melanoma. From there, we thought we could investigate whether high-concentrate hydrogen peroxide could have a similar shrinking effect on basal and squamous cell carcinomas before surgical excision.
The second catalyst for the project came from the practice pattern in our center, which is surrounded by a farming community. We saw a large number of people with head and neck skin cancers on whom we performed excisions and reconstructive surgeries, including skin grafting and local rotational flaps. Although cosmetic outcomes with these procedures are generally favorable, it’s always a good idea to minimize reconstructive surgery. Therefore, the prospect of using a topical solution to shrink the tumors and limit the incisions was of interest to us.
Goals and Methodology
Please briefly describe the methods and goals of the study.
The study’s goal was to discover whether a single application of 33% hydrogen peroxide to nonmelanoma skin cancers of the head and neck could significantly reduce tumor sizes prior to definitive surgical excision. We wanted to start the study with a proof-of-concept exercise to evaluate the safety profile associated with hydrogen peroxide.
It was a single-center case series study, for which we accrued 11 people with histologically confirmed nonmelanoma cervicofacial cutaneous malignancies. We carefully measured the width and length of 17 lesions and applied concentrated hydrogen peroxide to the cancer with a cotton swab, rubbing until the lesion blanched. The patients returned to our clinic several weeks later for a follow-up to remeasure the skin lesion and resect when appropriate.
We did notice a significant reduction in both the length and width of the skin lesions after a single treatment with hydrogen peroxide, and, in all cases, it simplified the surgical procedure and avoided the need for a local flap, which is always a good thing in head and neck cancers. Interestingly, for 53% of the lesions, [histopathologic analysis showed] there was complete resolution of the cancer after treatment with hydrogen peroxide. In those cases, we did not have to perform an excision and reconstruction procedure. More important, after 6 months of follow-up, we did not record any cases where the cancer recurred.
Besides a slight tingling, the patients had no side effects from the hydrogen peroxide treatment. The skin blanching that was observed during treatment did not last more than about 30 minutes, and the patients were able to continue with their daily activities.
Limitations and Implications
What were the takeaways from your study?
First, I need to point out that our trial was small—only 11 patients—so any result we arrived at should be looked at with caution. That said, we concluded that highly concentrated hydrogen peroxide is safe and well tolerated in treating these skin cancers. It’s also been shown that it could be deployed as an effective neoadjuvant treatment, as it significantly reduced the size of the lesions, and, in fact, it may be the only treatment patients need, obviating surgery.
The potential clinical implications are quite vast, and if our findings are validated, high-concentration hydrogen peroxide, which is inexpensive and easily accessed, could be used in the office and administered by a primary care physician, a nurse practitioner, or a dermatologist to patients who are waiting for surgical consultations about their skin cancer. There are many ways to use hydrogen peroxide in the clinic, and I think this primary research is going to open up interesting new pathways.
"There are many ways to use hydrogen peroxide in the clinic, and I think this primary research is going to open up interesting new pathways."— Neil Mundi, MD
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Why Now?
Given the simplicity of your study and the remarkable nature of your findings, why do you suppose it took until 2020 to initiate a study such as yours?
I think most individuals, and admittedly myself included until this study, have a hard time grasping that hydrogen peroxide has proven anticancer effects. If you hear that a common household chemical may be able to successfully treat a cancer, it seems like a very farfetched concept. So I think most people do not have the motivation to conduct a study that involves a lot of paperwork and time spent writing the grant application and accruing patients.
Ideas like this take time before they are processed and accepted by the medical community. It’s just part of the too-good-to-be-true skepticism that accompanies many new ideas.
Underlying Mechanisms
Do we know why high-concentrate hydrogen peroxide has efficacy in these skin cancers?
Although the exact mechanism of action is not known, hydrogen peroxide is a potent oxidizing agent that can exert a role in oxidative stress. Previous research has indicated that it may interact with hemoglobin in the dermal capillaries, producing oxidized forms of hemoglobin in the dermal capillaries, such as ferryl hemoglobin, which is highly reactive.4 Thus, hydrogen peroxide might cause necrogenous oxidation and oxygen-induced apoptosis in nonmelanoma skin cancers. That’s just one of many possible hypotheses.
Looking Ahead
Please share a closing thought on your plans moving forward.
During the data analysis for this study, we realized that these findings could be a springboard for more research in studying hydrogen peroxide in skin cancers. Now that we have established that hydrogen peroxide is safe in this clinical setting, we need to take it to the next level, looking at it in randomized controlled trials and comparing topical hydrogen peroxide with other topical treatments, such as fluorouracil. In addition, we could conduct a “wet lab” experiment to try to determine the exact mechanism of action of hydrogen peroxide, which could help motivate others in the scientific community to study this agent.
We followed our patients for 6 months, and I think longer-term follow-up will be beneficial, just to ensure there are no recurrences. Finally, I think we should look at the value and efficacy of multiple applications of hydrogen peroxide on skin lesions, as our study was based on just one application. So, the prospects for clinical benefit are exciting, given that these skin cancers are so prevalent among people in a wide age range.
Dr. Mundi is a Fellow in the Department of Head and Neck Oncologic and Microvascular Reconstructive Surgery at the Head and Neck Institute of Mount Sinai Hospital in New York. At the time the study was published, Dr. Mundi was with the Department of Otolaryngology–Head and Neck Surgery, London Health Sciences Centre, Victoria Hospital, University of Western Ontario, in London, Ontario.
DISCLOSURE: Dr. Mundi reported no conflicts of interest.
REFERENCES
1. Mohan SV, Chang AL: Advanced basal cell carcinoma: Epidemiology and therapeutic innovations. Curr Dermatol Rep 3:40-45, 2014.
2. Guy GP, Machlin SR, Ekwueme DU, et al: Prevalence and costs of skin cancer treatment in the United States, 2002-2006 and 2007-2011. Am J Prev Med 48:183-187, 2015.
3. Mundi N, Jordan K, Doyle P, et al: 33% hydrogen peroxide as a neoadjuvant treatment in the surgical excision of non-melanoma skin cancers: A case series. J Otolaryngol Head Neck Surg 49:33, 2020.
4. Giulivi C, Davies KJ: A novel antioxidant role for hemoglobin: The comproportionation of ferryl hemoglobin with oxyhemoglobin. J Biol Chem 265:19453-19460, 1990.
