Skin Cancer and Photoprotection: From Sunscreen to Field Therapy

The real culprit: ultraviolet light, UVA vs UVB

Almost every non-melanoma skin cancer is a dose-record of one thing: ultraviolet radiation. Sunlight carries two kinds of ultraviolet that reach the skin, and the distinction runs through this whole chapter. UVB is the shorter, higher-energy wavelength; it is absorbed in the epidermis and directly damages DNA — it is the main driver of sunburn and of the mutations that seed squamous and basal cell carcinoma. A useful mnemonic: UVB = Burning. UVA is longer, penetrates deeper into the dermis, and does its harm more indirectly, generating reactive oxygen species that age the skin and add to carcinogenesis: UVA = Ageing. Both contribute to cancer, so the goal of photoprotection is to block across the whole UV spectrum — "broad spectrum" — not just the wavelengths that redden the skin. This UV-damage theme runs alongside the Pigment chapter, where the same photons drive melasma and sun-triggered pigmentation.

How a sunscreen actually works

There are two entirely different chemical strategies hiding inside that bottle. Organic ("chemical") filters are carbon-based molecules — avobenzone, octocrylene, oxybenzone and relatives — that absorb ultraviolet photons. The molecule takes the UV energy, is bumped to an excited state, then releases that energy harmlessly as a tiny amount of heat. Each covers a particular slice of the UV spectrum, which is why modern products blend several to achieve broad-spectrum cover. Inorganic ("physical" or mineral) filters are different: zinc oxide and titanium dioxide are mineral particles that sit on the skin and reflect and scatter UV — and, in reality, also absorb a good deal of it. Because they are inert and sit on the surface, mineral sunscreens are the gentlest choice for children and for inflamed or sensitive skin, and zinc oxide in particular gives genuinely broad UVA-plus-UVB cover on its own.

What SPF really means — and why it usually lies

SPF — the sun protection factor — is essentially a UVB number: it tells you how much longer skin takes to redden with the product on. But two traps make the printed number misleading. First, the relationship is not linear the way people assume: SPF 30 blocks about 97% of UVB and SPF 50 about 98% — a small real-world gap, not the near-doubling the numbers suggest, and no sunscreen reaches 100%. Second, and far more important, the laboratory SPF is measured at a thick 2 mg/cm² application. Almost nobody applies that much — real-world use is often a third to a half of it, which drags the true protection down disproportionately. So the practical rules matter more than the number on the bottle: apply generously, reapply every two hours and after swimming or sweating, and never treat a high SPF as a licence to stay out longer. And note the number says nothing about UVA — for that you rely on the "broad spectrum" label (or star / PA ratings, depending on region).

Field cancerisation: treating skin, not spots

Actinic keratoses are the visible tip of a much larger iceberg of sun-damaged skin. An actinic (solar) keratosis is a rough, scaly patch of atypical keratinocytes — a pre-malignant lesion, a small minority of which progress to invasive squamous cell carcinoma. But the crucial concept is field cancerisation: the sun did not damage a few tidy spots, it mutated a whole area of skin, so that the visible keratoses sit in a much larger field of sub-clinical damage primed to erupt into new lesions. This reframes treatment. Freezing (cryotherapy) each visible keratosis is fine for a lesion or two, but it ignores the field. When the whole area is affected, dermatology reaches for field therapies — topical agents spread across the entire region to treat the visible and invisible damage together. Each works by a different, exam-worthy mechanism.

The field therapies and their mechanisms

Four topical strategies, four completely different ways to clear a sun-damaged field. 5-Fluorouracil (5-FU) cream is a topical antimetabolite. It is fluorinated uracil that, once inside cells, blocks thymidylate synthase — the enzyme that makes the DNA building block thymidine — so rapidly dividing atypical keratinocytes cannot replicate their DNA and die. Normal skin, dividing slowly, is relatively spared, which is why 5-FU selectively "burns off" the damaged field, producing a brisk, alarming-looking red, crusted, inflammatory reaction that signals it is working. This is the exact same molecule and thymidylate-synthase mechanism used intravenously against colorectal and other cancers — a direct link to the Antimetabolites chapter, here delivered to the skin surface. Imiquimod works by a wholly different route: it is an immune activator, an agonist at Toll-like receptor 7 (TLR7) that switches on the local innate immune response, driving interferon and cytokine release so the patient's own immune system destroys the atypical cells. (The same imiquimod, and the same TLR7 trick, treats genital warts — cross-referenced in the Viral chapter.) Diclofenac gel is a topical NSAID; by inhibiting cyclo-oxygenase (COX) it dampens the prostaglandin pathway that abnormal keratinocytes rely on — the gentlest, slowest option, with the least inflammation. And photodynamic therapy (PDT) is a two-step trick: a photosensitising pro-drug, aminolevulinic acid (or its methyl ester), is applied and selectively taken up by the atypical cells, where it is converted to protoporphyrin IX; shining the right wavelength of light on it then generates a burst of reactive oxygen species that destroys those cells — chemotherapy triggered by a lamp.

Superficial non-melanoma cancers: topical options and the hedgehog pathway

Basal cell carcinoma (BCC) is the commonest human cancer — slow-growing, locally destructive, almost never metastasising. Most are simply excised (and a low-recurrence surgical technique called Mohs surgery is used for tricky facial tumours), but pharmacology enters at both ends of the spectrum. For a thin, superficial BCC, the same topical field agents — imiquimod or 5-FU — can clear the tumour without surgery. At the opposite extreme, locally advanced or metastatic BCC that cannot be cut or irradiated is treated with a targeted drug class built on the tumour's own biology: hedgehog-pathway inhibitors. Nearly all BCCs are driven by inappropriate activation of the Hedgehog signalling pathway, usually through loss of a brake called PTCH1, which leaves a signalling protein named Smoothened (SMO) permanently switched on. Vismodegib and sonidegib are SMO inhibitors — they plug the stuck accelerator and shut the pathway down. Their characteristic side effects flow straight from blocking a pathway the body still uses: muscle spasms, hair loss, and taste disturbance (dysgeusia), and they are strictly teratogenic, so pregnancy must be excluded and prevented.

Melanoma and advanced disease: where dermatology hands off to oncology

Everything above is dermatology's turf. Invasive melanoma is where the baton passes. Early melanoma is cured by excision, and that is dermatology's job — catch it early, cut it out. But once melanoma spreads, treatment moves into systemic oncology, and the last decade transformed it as dramatically as any cancer in medicine. Two systemic strategies dominate. About half of melanomas carry an activating BRAF V600 mutation that locks a growth-signalling pathway on; these respond to targeted BRAF inhibitors (such as vemurafenib or dabrafenib), almost always paired with a MEK inhibitor (trametinib) downstream to delay resistance. The other pillar is immunotherapy — the immune checkpoint inhibitors (anti-PD-1 pembrolizumab or nivolumab, and anti-CTLA-4 ipilimumab) that release the brakes on the patient's own T cells. Melanoma was the flagship success of that entire class. This chapter deliberately does not re-teach those drugs — the mechanisms, the biomarkers, and the immune-related adverse events live in the Oncology section, and the BRAF/MEK and checkpoint stories are told there in full. The dermatologist's role is to recognise melanoma, stage it, and refer; the pharmacology of the invasive disease is oncology's.

The high-risk patient: transplants and immunosuppression

One group deserves special mention because it ties this chapter to the rest of pharmacology: solid-organ transplant recipients. Kept on long-term immunosuppression to protect the graft, their weakened immune surveillance lets sun-driven skin cancers — especially squamous cell carcinoma — arise far more often and behave far more aggressively than in the general population. For these patients photoprotection is not cosmetic advice but essential preventive medicine, and their whole skin needs regular surveillance. This links straight to the Immunosuppression chapter, where the very drugs that save the transplanted kidney (calcineurin inhibitors, antimetabolites) are the reason the skin becomes a cancer field. It is a clean illustration of the immune system's double role: the same checkpoint-inhibitor era that rescues melanoma patients also reminds us that a suppressed immune system is a skin-cancer risk, and a released one is a cancer treatment.