Hydrogen Peroxide Appears to Treat Pre-Cancerous Oral Lesion in “N-of-One” Experiment

Numerous patients come to Cancer Commons because they wonder if their best cancer treatment option may lie beyond standard care. For many patients, this will mean receiving treatment through a clinical trial. However, with the input and supervision of their medical care team, a select number of patients may arrange to try a non-standard treatment outside of a normal clinical trial. This approach is often called an “N-of-one” experiment, because it is like a clinical trial where the number of participants (N) is just one—the patient.

Here, our Curious Dr. George speaks with Ronald Piana about an N-of-one approach he took to treat his own oral leukoplakia, a condition that can develop into oral cancer. Ronald Piana is a freelance science writer specializing in oncology.

Curious Dr. George: In a recently published study, Neil Mundi, MD, of the University of Western Ontario and colleagues reported success in minimizing or even eradicating biopsy-proven non-melanoma cutaneous malignancies by the topical application of concentrated hydrogen peroxide. You had a similar recent experience with an oral premalignant lesion in an N-of-one clinical trial. What was your experience?

Ronald Piana: In 2018, during a routine dental examination my dentist discovered a small whitish patch on the left lateral border of my tongue. He ordered a biopsy, and the lesion was diagnosed as benign leukoplakia. The lesion recurred and progressed, and approximately 1 year after the initial diagnosis presented as a raised, red-white lesion about 3 cm in diameter that was causing discomfort. On follow-up, my dentist found the lesion “very concerning” and scheduled a consultation with an oral surgeon.

I’m a 25-year veteran science writer in the oncology sector, and I’d chanced to read Mundi’s study, in which he and his colleagues successfully treated non-melanoma skin cancers with topical 33% hydrogen peroxide (H2O2). I decided to do an N-of-1 experiment on my oral lesion. I brushed the lesion until blanching with a cotton swab soaked in a solution of 35% H2O2 twice a day for 2 days prior to my appointment. At the appointment, the oral surgeon viewed a digital image of the lesion obtained by my dentist and prepared for excision. Upon oral examination, however, he found no evidence of the 3 cm lesion. On 3-month follow-up, no visual indication of recurrence could be detected.

Curious Dr. George: What biological effects might explain the result?

Ronald Piana: Hydrogen peroxide is a well-established apoptosis-inducer with broad cytotoxic activity in a range of cell types. Other H2O2 cytotoxic pathways have been identified, such as lysosomal membrane permeabilization (LMP). In LMP, the lysosome (described as a “suicide bag”) is compromised by H2O2-driven oxidative stress, during which large amounts of H2O2 enter the lysosomal compartment, forming abundant hydroxyl radicals, or highly reactive iron-centered radicals, which leads to degradation of cellular structures and, ultimately, cell death. Yet another intriguing explanation considers the Warburg effect, wherein transformed cells, such as those in cutaneous malignancies, undergo a shift from oxidative to glycolytic metabolism, rendering cells more susceptible to H2O2-induced oxidative stress. H2O2 has other cytotoxic pathways, yet, in short, this potent agent kills cancer cells by inducing oxidative stress.

Curious Dr. George: What do you propose as next steps?

Ronald Piana: Mundi’s study is the first in the literature to evaluate high-concentrate H2O2 as a topical treatment for cervicofacial cutaneous malignancies. The results have broad health implications for the millions of Americans diagnosed each year with skin cancers, and further indicate that topical H2O2 treatment could be a valuable clinical option for a variety of healthcare professionals including surgeons, dermatologists, and primary care physicians. Therefore, I hold that prior investigative work coupled with findings from Mundi, et al., should be viewed as proof-of-concept in safety and efficacy leading to larger scale evaluation and recognition of topical H2O2 as a treatment option for select carcinomas and, equally important, opening the investigative door into other exciting clinical opportunities.

My concern is that further serious investigation of this cheap and readily available agent, for various reasons beyond the scope of this post, will be ignored or rebuffed by the research and medical communities. To that end, I encourage others in the healthcare community not to let this valuable clinical opportunity pass.

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