Skin Cancers - Pre-cancers, Prevention and Keeping them at bay.
Skin Cancers, Pre-cancers, Prevention and Keeping them at bay.
As with cancers anywhere, there are a few that tend to affect one area in particular, and skin is no exception. Skin-cancers are usually grouped into either melanoma-type or non-melanoma-type. Melanomas are nasty and need to be dealt with fast. Non-melanoma-types can be nasty too, but are much more likely to be less serious.
There are always anomalies to any statistics and no set of statistic are going to describe you, or any individual, because they are a snapshot of a bird’s eye view of ‘most people’ so they just describe the average of lots. As many people will have some sort of skin cancer, especially if we’re all determined to live into our 90s, we shuould all start good skin-care habits earlier to help avoid common cancers, which commonly occur! Before detailing the cancers, it’s good to remember that we already have two very effective protective shields, that both need looking after: our skin barrier and the ozone layer.
Natural Protection in Skin - Melanin
Look after your skin and it will continue to do a pretty impressive job of protecting itself from all sorts of injuries, including pre-cancerous, benign and cancerous growths. Understanding how it does this, helps when deciding how to take care of it.
One of the most important protective functions the skin has is an ability to produce melanin. This is a pigment produced by melanocytes cells, responsible for the colour of skin, hair, and eyes and it provides protection against UV radiation. Some people have lots of melanin, and other people have little; it is a genes-thing, so you will know from your relatives and your relative colour where you are on the melanin graph -probably somewhere between pale pink and deep brown. Some people’s melanocytes don’t produce melanin, or just minuscule amounts. This is due to a genetic mutation that causes albinism. There are different forms of it and they vary in severity. Worldwide, about 1 person in 20,000 has albinism. It gives people a very pale appearance, to eyes and hair too. The prevalence is highest in African countries, where as many as 1 in 5,000 people have it. These people need to avoid sunlight as this vital barrier is missing, making their skin very vulnerable.
Melanin v The Sun
Having melanin allows the rest of us to lead comfortable lives outside in daylight. Melanocytes that function normally, respond as soon as sunlight hits the skin, instigating signals to be set off, which ask for extra melanin to be sent up to the surface. This melanin adds a layer of protection, so a suntan is evidence of where the skin has protected itself from UVB light. This is clever, but not foolproof; a lot of sun in one go can overwhelm the melanocytes demand for melanin and the skin will burn. As we age, so melanin production can get a bit sporadic; it can be over-enthusiastic in some areas and leave other bits to fend for themselves. The result looks like little islands of dark brown splodges sitting on otherwise even-coloured skin, or lots of little freckly areas over the skin. The melanocytes learn where the previous skin damage is and keep deliveries coming there - so scars, even superficial ones, tend to be darker. Melanin is great, but a tan is not enough of a barrier against UV radiation, but it is a reminder of where the skin has tried to protect itself.
Part of how melanin protects the skin is in absorbing the UV rays and converting them into heat, which then wafts off, back into the air. This conversion stops the rays from penetrating down to the deeper layers, where the precious DNA lives - if it causes damage to those cells, the results will be eventually become visible. Genes instruct the body’s DNA to make new cells, to replace those that reach the end of their lifespan, they do this by copying and replicating themselves. If a mutation affects one of your genes, your DNA won’t have the instructions to make new cells as it should, instead they mutate which means that as skin cells replicate themselves in new cells, they contain flaws: producing flatter, misshapen and less well functioning skin cells, or just lots, all stuck together. This make skin look lined, have dry patches, sagging and stretched-looking skin. The function is also slower and less efficient. The skin anomalies make cancers more likely. Even people with lots of melanin can still burn and damage skin through sun exposure. Both prolonged sessions in sunshine and exposure to very hot sun can overwhelm the body's natural defences.
Countries with the lowest rates of skin cancers include some in Asian and Africa, in particular, sub-Saharan Africa. And there’s no prize for guessing that Australia has one of the highest rates. The sun there can be very hot, for prolonged periods and the majority of people living there have predominantly fair skin (Fitzpatrick skin types 1 to 3)and there is an ‘outdoor culture’ which means time spent outside in spring and summer. The Australian Aboriginal and Torres Strait Islander peoples, who tend to have more melanin and fall into Fitzpatrick skin types IV to VI, make up about 3% of Australia's total population and they suffer less from skin cancers.
The other natural protection is provided courtesy of the ozone layer…
The Ozone Layer
There is about 3 billion metric tons of this sitting twenty miles above our heads. Ozone in the stratosphere absorbs most of the dangerous UV light, which protects all life on earth, not just us, from obliteration! It screens us from all of the most energetic, UVC rays, most of the UVB rays and about half of the UVA rays. Unfortunately we humans have done a reasonable job of making a hole in it, sending up our unwanted molecules of nitrogen, hydrogen, chlorine and bromine. This hole sits primarily over Antarctica, during the Southern Hemisphere's spring (September to November) and it has lead to increased levels of UV light reaching us and so increasing the prevalence of skin cancers (and cataracts). Efforts to reduce ozone-depleting substances, have resulted in significant progress, so the hole is at least now growing more slowly. But mending it will take a while and for the time being, this hole means there is less protection in some regions, and Australia, during the spring, can see the protective layer reduced by about 5%. Due to this, Australia has seen a significant rise in the incidents of skin cancers in the last thirty years. They took the initiative and campaigned for skin health education and skin cancer prevention, which has worked. As a result the population understands sun-protection better than many other countries, and so they have become good at protecting and understanding their skin and tend to detect skin cancers earlier there.
So, the cancers - I probably don’t need to remind anyone, but just in case, before we get into them… if you have grown anything strange on your skin, or you have a mole that has changed, please show it to a doctor. The main difficulty in answering questions about skin, is that I can’t see it. If we’re discussing acne, I have a good idea of what’s being described, but cancer isn’t acne. Skin cancers are in another league, (just a flick through Rooks Handbook for Dermatology quickly demonstrates how similar a benign actinic keratosis and a life-threatening melanoma can appear). There is no simple description of any skin cancer I could write, that you could confidently use to decide what you’ve got. Even the experts, who see lots, daily, will almost always send a standard-looking squamous cell carcinomas off for analysis. The reason for the precautions and warnings is that some of the most innocuous looking lumps can metastasise, and they can do it very fast. Meanwhile, others can look like a patch of 14th century plague, but actually, it’s only superficial, not going anywhere, just being a bit warty. But you need to know which yours is. At the bottom, I have added a simple mole check that I put up in 2019 - but that’s just moles and it’s an at-home-check, not a definitive diagnosis. (Only 20 to 30 percent of melanomas are found in existing moles, up to 80 percent arise on apparently normal skin).
So, the nastiest first: Melanoma
The incidents of these are generally lower in countries with less intense sunlight exposure, so Northern Europe, Scandinavia and Canada, and countries where people are accustomed to covering their skin whenever they are outside. The education and awareness of melanomas and the need for broad-spectrum sun-cream is now much better understood, with a beneficial effect. However, there is still a belief that people with darker skin are unlikely to suffer, but this is untrue. People of African, Asian, Latino, Middle Eastern and Native American descent tend to report subtle skin changes less often, but a thorough yearly check is still necessary. Melanomas, unlike some of the other skin cancers, more often appear on the trunk and legs, than on the face (according to the Skin Cancer Foundation, women develop them most often on the legs and on men, its the trunk. Although in Black, and Asian people melanomas most often occur on nonexposed skin, up to 75 percent are found on the palms, soles, mucous membranes and nails. Anyone non-white is most like to find them on the plantar portion of the foot (up to 40%). But these are statistics, which are general trends, a melanoma can appear anywhere you have skin - whether it’s a bit that has been in the sun regularly or not). Over 50, significantly more men than women develop melanomas and white men over 55 are the majority group to develop melanomas and 1 in 28 will develop melanoma at some point, (according to Skin Cancer Foundation).
If you have had more than 5 episodes of sunburn, you are twice as likely to develop a melanoma. Sunburn means: any or all of the following: the skin has become red, inflamed, peeled, or painful to touch. If you do develop one, getting to a specialist fast is likely to lead to a complete recovery; 99% of melanoma patients will survive longer than 5 years and many a lot longer. (5 years has become the timeframe accepted that cancers are in remission, but there isn't a universal standard; it is primarily because the risk of recurrence tends to decrease significantly from this point.)
Progression of a Melanoma
Melanoma begins in the cells that bring up the melanin to the surface, the melanocytes. It starts up in the epidermis and this is when you might see a mole or freckle start to look different. They can itch as the melanoma cell breaks the protective skin membrane between the epidermis and the dermis as this often causes localised swelling or bleeding. If the melanoma gets through the basement membrane, it is possible for it to enter blood and lymphatic vessels which can transport it around the body. From here they can lodge in small blood vessels and grow into secondary, metastatic lesion in other organs.
A Rare But Nasty One - Merkel cell Carcinoma (MCC)
First discovered by Freidrich Merkel, Merkel cells are deep inside the epidermis and are a neuroendocrine cell, so they have both a nervous system and endocrine system. MCC is very rare (about 10 in a million people), although becoming more common recently, probably due to better education around skin cancers in general. It affects mainly older people and those with pale skin and eyes. It is aggressive and needs to be treated quickly.
Non-Melanoma Skin Cancers:
We are now able to treat non-melanoma skin cancers fairly routinely and people are much better at spotting and reporting them. Treatment of these skin cancers increased by nearly 80% between the mid 90s and 2015 in the US. Consequently, the numbers having treatment are large; over 5 million people a year are treated annually now (more than all other cancers combined in US), and 90% are caused by UV light exposure. Far fewer people die from non-melanoma cancers, but a number of people still will - roughly 60,000 people yearly, worldwide.
Basal Cell Carcinoma (BCC)
This is the most common form of skin cancer and is often linked to cumulative sun exposure, especially any during childhood. Like other skin cancers, these unusual cells begin to grow as the DNA is affected and this will happen more readily if skin has been exposed to UV light for long periods or to very hot sunshine. Instead of making perfect copies when each new basal cell is made, the process piles up lots together, rather than cleanly moving on to the next cell. This manifests on the surface in clumps of extra skin cells, piled up together, instead of lying flat across the surface.
It affects more men than women and mainly people over 50 (although there is a rare inherited condition -basal cell nevus syndrome where BCC will appear in children). Those with fair skin and light eyes are also more likely to be affected and anyone who has already had one skin cancer confirmed is at a higher risk of others.
BCC originates in the basal cells, which are found in the lower part of the epidermis.They often start looking like a small, shiny lump, as if the top has been scarred or burned and become translucent. Importantly, if this is a BBC, it will begin to grow, it may appear to heal for a short time, but break down again. They are typically slow-growing and do the damage locally, not systemically. If left, they begin to look like ulcers and may crust but won’t heal, the scab can come off in pieces, and it often bleeds before reforming. It can eventually begin to erode down through the skin layers, even reaching subcutaneous tissues. It rarely metastasises, but if left untreated, after reaching these deeper layers it can become more aggressive and burrow deeper still and so spread. They typically grow on the face, especially the bridge of the nose, the top of ears and on the scalp.
4 Types of BCC
There are four main types: The most common is Nodular: It starts as a rounded shaped spot on the skin, as it grows little blood vessels are visible around it. Superficial spreading BCC: These start as slightly dipped, shallow areas of skin that have less melanin that the surrounding tissue. Unlike melanoma, they tend to be easy to treat, but they are often found in similar places to melanomas, like the trunk and legs. Sclerosing: This third type often appears on the face and looks like the skin has been nicked or scarred or it could be just a raised red dot. Like other BCC, they tend to expand into surrounding tissue, but not down into deeper layers of the skin. Occasionally BCC are Pigmented: These are rare and just appear as any area of hyperpigmentation might.
How To Treat BCC
Most often and pretty straightforward is to have the lesion frozen to remove it, a treatment called cryosurgery. Alternatively it can be scraped and/or burned with electric current Electrodessication. This is not usually painful as the skin is anaesthetised. If this isn’t suitable or the area is large, then surgery will be necessary - the BCC will be cut out and skin pulled to cover the area. Blue light Photodynamic therapy and Laser Therapy are two relatively new treatments - using light or a laser to remove the cells. It is very rare for a BCC to spread and require strong medication to treat it. If it has spread and become a systemic problem, chemotherapy may be necessary, to kill all the cancerous cells in the body. Vismodegib (Erivedge) is used when it has become metastatic and Sonidegib (Odomzo) when it is advanced but not yet metastasised.
Squamous cell carcinoma (SCC)
The second most common form of skin cancer, usually form on areas most exposed to UV light, so, face, ears, nose, hands, arms, legs and back, but also includes the mucous membranes, particularly lips (cheilitis) a sore on the inside on the lip, often paler than the surrounding tissue. SCC that just affects the top layer of skin is cutaneous, and although it rarely spreads, but if it spreads beyond the skin, it can be metastatic.
This affect a similar group to BCC: those who have had particularly frequent sun-burn, especially during childhood or long periods in the sun. Those with pale skin, (Fitzpatrick types 1, 2 and 3) and more often over 60, but younger people are being diagnosed more often in the last ten years. Anyone who has used an indoor sun-lamp/tanning beds or solarium, smokers or a compromised immune system. Men are twice as likely as women to present with it. It is far more frequently diagnosed now, up over 100% in ten years, partly due to better awareness and education of the condition.
It can present as a lump with an indented middle, a lump or a sore that forms a scab, bleeds and doesn’t heal, or returns quickly after healing over. It can also appear as a flat, scaly, often red area of about 2.5cm. It can begin as actinic keratosis (see below). It is also caused by damage to the DNA layer. A mutation in the gene that suppresses the rate and number of cells dividing and replicating. When damaged, this gene then allows too many cells to divide and replicate too often and this leads to a build up of cells that clump together forming lesions and can cause tumours.
There are several stages to a SCC, the first is ‘in situ’ when only the top layer of the epidermis is affected. If it has travelled down as far as the dermal layer, this is a stage 1 cancer, at stage 2 the nerves and subcutis are also affected and if it has leaked from here to the lymph nodes, it is then able to spread and is at stage 3. If it has metastasised, it will affect other organs.
How To Treat SCC
The treatment is very similar to BCC - freezing with cryosurgery; being scraped and/or burned with electric current Electrodessication and curette to scrape off the lesion; Blue light Photodynamic therapy and Laser Therapy - using light or a laser to remove the cells. If it has metastasised, chemotherapy may be used.
A cream with 5-fluorouracil, that goes under several trade names: Adrucil, Efudex, Fluoroplex, Fluracil can treat SCC if it is just in the epidermis and still contained in the skin layers. A more advanced lesion may require, a monoclonal antibody medication or immunotherapy is sometimes used -Cemiplimab-rwlc (trade name Libtayo - there may be other names I don’t know).
So… all the above need to be seen by a specialist who will advise on treatment. But, there is much that comes before these stages begin and we can stop most from developing.
What We Can Do To Avoid Skin Cancers:
- Stop them before they start:
Wear a broad-spectrum suncream - broad spectrum means that it protects the skin from both UVA and UVB (the ozone pretty much takes care of all the others, including UVC). It should be Factor 30 or above when outside in sunshine. It is important to cover all exposed skin and be aware that it will rub off as you go about your day, so be ready to reapply it every few hours, if necessary.
Use sunglasses, with UVA and UVB protection (the label should say 100% UV protection or UV400 protection). People sometime forget that eyes are affected by sunlight too. Sun exposure can cause cataracts and other eye damage. The eye lens is made up of proteins and prolonged UV exposure can cause them to become opaque, like an egg white as it heats.
Use clothing and broad rimmed hats where practical - it doesn’t cost anything to choose a long-sleeve shirt and hat as you leave to venture outside and shade is the best way of avoiding sunshine.
Better still, if you can do what you do inside, when the sun is hot, try to arrange that. Depending where you are in the world between 11AM to 3PM, these are usually the hours most likely to find a sun that can do damage. If you have very pale skin, add an hour either side, but more importantly, learn what you skin can and can’t deal with and if your skin begins to redden at 9.30 on a sunny morning, then make sure you don’t go out uncovered then.
I have a bit of a problem with the price some manufacturers charge for very simple suncreams and the finger-wagging, somewhat evangelical attitude they can bark at us - it is in danger of making people cynical and then presume it’s all marketing hysteria. In the UK and US sun creams are considered over the counter drugs (OTCD) so the claimed level of protection against UV will need to have been proved, as will their ‘broad spectrum’ protection status and water resistance. So if it’s on sale anywhere reputable it should be reliable, more expensive doesn’t do the job any better.
You don’t need to apply it if you’re not going out in sunshine, (yes, you can tan on cloudy days, but probably not in Norway…) so, learn your skin-type, what the sun strength is wherever you are and take responsibility to cover your skin as and when necessary. Try not to let marketing terrify you into covering every inch in creams that, whilst good at keeping the sun out, may not be great for your skin for 18 hours daily. I prefer the physical blockers like zinc oxide and titanium dioxide; we can manufacture creams using them now that don’t leave everyone with that bright white 1980s skiing hue. Some older formulations contained ingredients that raised concerns about potential endocrine disruptors, but these are rarely used now. We don’t want to get any cells mis-firing, but we do need vitamin D too - it is very useful stuff and is synthesised in the skin when it is exposed to UVB light. The higher the SPF, the better a cream will block vitamin D. (Any sunlight will deliver vitamin D, it doesn’t need to be strong).
Ways To Sort Actinic Keratosis and Pre-cancer lumps.
AK isn’t a skin cancer, they are benign growths in the epidermis. A small percentage, if left untreated can develop into squamous cell carcinoma - roughly 10%, if left untreated, will become SC within 10 years.
As with all the cancers, AK are usually found on areas that have seen the most sun, so, the head, chest, arms and legs. Because the are so prolific, there is a better general understanding that we should get rid of them. The drug companies have pulled out all the old drugs for trials on these and lots have found success. Fourouracil (a drug from 1962) was trialled with some success (2 x daily for 6 weeks cleared lesions in 45% of patients). Rapidly growing cells need thiamine and by applying a fluorine atom, it simulated thiamine, so the cells were fooled into thinking it was thiamine and soaked it up, but instead of feeding the cells it poisons them - mean, but clever!
Another older drug, Diclofenac (aka Voltaren, Cataflam, Diclomax, Diclozor…) has been used for years by athletes as a gel to soothe sore muscles. This was mixed with hyaluronic acid, to provide the water retention necessary to draw the drug further down into the skin where it can be effective. It was also trialled on AK and seemed to work (2x daily for 60 days apparently cleared lesions in 30% of patients and for 90 days 50% of patients - but using it for longer had no additional benefit). It reduces inflammation and increases cell turnover. It may also reducing prostaglandin synthesis, inhibiting oxygenase which ‘feeds’ skin cells. (It would be interesting to know if the patients it didn’t help had anything significant in common - I don’t know.)
Basically, AK need to be dried out or sloughed off and as long as healthy skin is kept unaffected, how we do it can be varied, lots of things will work, to a degree. Dr Guba, an Australia doctor with a special interest in essential oils, has had success using a-santalol, found in sandalwood in a recipe. This seems to disrupt the cell membranes of the AK, so they can no longer function and so die.
Azaleic acid, a naturally occurring organic compound derived from grain also works (it has good anti-inflammatory and antimicrobial properties) we usually use it on rosacea. All of the Alpha Hydroxy Acids will do the trick too, just by drying out and sloughing off the surface layer (lactic acid, glycolic, malic etc). but they can be harsh and the concentration needs to be carefully controlled. They may be a bit of a blunt instrument - but as long as the skin is otherwise kept protected and well moisturised, it shouldn’t be too uncomfortable.
Prevention - Before AK Arrive and After they're Zapped - Keeping Them At Bay.
The after-treatment is when people can slip back into not thinking about prevention…until we find something unwanted growing again. It’s probably good system psychologically, but bad dermatologically! The problem with any treatment is that it just removes the affected cells, it doesn’t stop more arriving. As soon as the skin is exposed to oxidisation again - so UV light in particular, these cells will likely return, more likely after having had AK. So skin needs to be strong and well protected.
I spend more than half my time as a formulator working on exactly this - ways of strengthening the skin to prevent AK and pre-cancerous growths. The main ingredients we use are to good affect (and with solid research): retinol/retinyl palmitate (retinoic acid in its various forms). CoQ-10 (a great antioxidant; Vitamin C with Ferulic acid, another good antioxidant, protector. We use a lot of plant extracts, particularly for the phytochemicals they offer. Green tea, honeysuckle and Resveratrol are some of our standards, to help neutralise the free radicals generated by UV radiation (free radicals contribute to skin damage). Niacinamide was the forgotten B vitamin for a while, but it’s almost having a moment, and it’s well deserved - this goes in most serums and creams I make to strengthen the skin’s barrier function. It is not always obvious that the ingredients working hard at maintaining hydration: hyaluronic acid, sodium hyaluronate, sodium PCA etc are also part of this prevention. Well-hydrated skin is much better at protecting itself as the skin barrier functions more efficiently.
For existing skin lesions, there is always the prescription medications (mentioned above - 5-fluorouracil (5-FU), imiquimod etc. Alpha Hydroxy Acids (AHAs) will exfoliate the skin's surface and help to remove damaged skin cells. Lactic acid when used with Niacinamide can increase ceramide formation.
And finally…Don’t Forget The Diet…
You may not be ready to go the full Bryan Johnson yet, but a diet of fresh food, rich in vitamins and minerals, low in sugar and preservatives, will go a long way to helping protect skin and mend it when it needs help. People who take in enough vitamin C daily (and it must be daily) don’t notice much difference when using it topically - this is because the skin is already saturated. So if you can eat it, you won’t need to add it anywhere else.
(For those interested - how sandalwood works)
Sandalwood treatment of HaCaT keratinocytes results in a blockade of cell cycle progression as well as a concentration-dependent inhibition of UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, these effects were not mediated through an inhibition of signaling upstream of AP-1, as sandalwood treatment did not inhibit UV-induced Akt, or MAPK activity. *Low concentrations of sandalwood were found to induce HaCaT cell death, although not through apoptosis. However, plasma membrane integrity was severely compromised in sandalwood -treated cells, which may have led to cleavage of LC3 and the induction of autophagy.
*By low concentrations of sandalwood - I believe this is between 2% and 13%
The Mole Checker - ABCDE
Moles commonly occur and are not diseased skin and are usually nothing to worry about.
It is worth checking the “ABC” of mole-watching to be sure that what you are describing is, in fact, a mole and not a melanoma or some other skin irregularity that need treatment.
A- is it a-symmetrical? (It should be roughly the same each side, if you were to draw a line down its centre.)
B - is the border even? (A smooth border is typical, an uneven border is a possible reason for concern.)
C - is the colour fairly even throughout the mole ( no big dark bits)?
D - is the diameter more than 5mm? (most are up to this size)
E - has it ‘evolved’ recently? Have you noticed changes? Particularly if the colour has darkened, the shape, the size or amount it protrudes - any of these could be a reason to get it examined.)
The concern is, whether it is indeed a mole or something that requires medical attention. If you’ve had it since you were a child, it doesn’t itch, or bleed and hasn’t become ulcerated and the ABC is all checked, you can be pretty confident that this is a common, all-garden mole! They can grow and change colour, but tend to do this in an even way. If you have a history of melanoma, or anyone in your family has had one, there is more reason to watch any moles more carefully (just every month or so, run through the check-list).
As a mole is benign (made up of nevus cells) you cannot have them removed as a necessary medical procedure - you will have to pay to have it surgically removed, which will leave you with a small scar.
Please don’t try to remove it with anything caustic (please don’t try to remove it with anything!) as you could make it very unhappy and unsightly and that would require medical intervention.