Supermarkets, foreheads and PD-1 inhibitors

As I left the supermarket last Friday night, the squamous cell carcinoma caught my eye as I zipped down the escalator. It wasn’t a large tumour but was very prominent on the man’s forehead—an open sore on a raised wart-like lesion. Fascinating.

A classical presentation in an elderly man on a sun-exposed surface. So, what’s the story? I have recently completed a course of topical 5-fluorouracil on my own forehead to remove two actinic keratoses, the precursors of these relatively common squamous cell carcinomas. A brutal treatment, but effective. It burnt my forehead off literally, and I am now the proud owner of a new forehead. In my 50’s now, it is the closest I will get to having young, wrinkle-free skin on my face and I am running with it, and with factor 50 sunscreen to make sure it stays that way and there is no recurrence.

But what of the chap on the escalator? The vast majority are curable, but for something like 1 in 20, the spectre of metastatic disease and subsequent death is real. These skin cancers are primarily caused by cumulative, long-term exposure to ultraviolet light from the sun and are distinct from other squamous cell carcinomas, such as in the throat or genitals, that are usually linked to the human papillomavirus or smoking. The sunlight is mutagenic, and the squamous cell tumour mutation frequency is one of the highest ever seen across cancers, and higher than melanoma. And therein lies a clue to a new treatment—the high tumour mutational load identifying these tumours as potentially responsive to immunotherapy. So, it has proven to be, with some complete responses reported in clinical trials of PD-1 inhibitors and with one drug recently licensed for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma.

The avenue of immunotherapy has profoundly changed the treatment paradigm for many advanced cancers, but this is only the beginning. There is much to be done, much to be learned and much to be communicated and I am excited to be working at this edge of clinical medicine.

EDGE—communicating evidence, changing clinical practice