Skin Cancer

Skin cancer was common in Hong Kong, among which, non-melanoma skin cancer accounts for over 90%. Non-melanoma skin cancer ranked tenth common among males, and eighth common among females in 2021.

In 2021, there were 1,094 new cases of non-melanoma skin cancer, accounting for 2.84% of all new cancer cases in Hong Kong. The crude annual incidence rate of non-melanoma skin cancer per 100,000 Hong Kong population was 14.8.

The incidence rate of skin cancer in Hong Kong is much lower than that of the Western countries. However, the local number of new non-melanoma skin cancer cases rose significantly by 41.3% from 2011 to 2021.

Although the incidence of skin cancer is high, its mortality rate is relatively low. Since the skin is the most visible organ, most abnormalities can be easily detected.

If any unusual skin changes are noticed, please visit a doctor as soon as possible. Early detection increases the chance of successful treatment.

What is skin cancer?

• Structure and function of the skin
  • The skin is the largest organ of the body. It consists of three parts: epidermis, dermis and subcutaneous tissue.
  • The epidermis consists of three types of cells: keratinocytes, Langerhans cells, and melanocytes.
  • The skin protects the body from foreign agents, lowers the temperature by sweating and prevents dehydration.
• Carcinogenesis
  • Skin cancer is mainly caused by Ultraviolet rays (UV).
  • The main source of ultraviolet rays is sunlight. The second is UV lamps from fitness and beauty centres.
  • There are three wavelengths of UV, UVA, UVB and UVC. While UVB is the main mutagenic cause of basal cell carcinoma and squamous cell carcinoma, UVA, which is released in large amounts by tanning beds, mainly causes melanoma.
  • UV damage to skin is accumulative. Even without sunburn, skin tissues will still be injured after prolonged exposure.
  • Previous studies suggested that if skin cells have been damaged at a young age, lack of proper UV protection in adulthood will cause the damaged cells to mutate.
  • Skin cancer often appears in areas that are exposed to sunlight, such as the face, lips and neck. However, it can also appear in areas not likely to be exposed to sunlight, such as the palms, soles and gaps between toes.
  • Skin cancer which occurs in areas away from sunlight may have genetic factors.

• Number of moles, which is more than usual
• Presence of macule
• Family history of melanoma
• Long working hours under the sun
• Frequent sunburns, especially with peeling skin
• Frequent use of tanning beds
• Light-coloured skin that is hard to tan but can easily be sunburnt
• Red or blonde hair with light-coloured pupils
• Immunocompromised e.g., received organ transplantation or HIV positive
• Burnt, injured skin or receiving treatment for other skin diseases
• Close encounter with chemical carcinogens

Skin cancers are classified into:

• Non-melanoma skin cancer
  • Basal cell carcinoma
  • Squamous cell carcinoma
• Melanoma

Non-melanoma skin cancer

• Non-melanoma skin cancer includes basal cell carcinoma and squamous cell carcinoma.
• Basal cell carcinoma and squamous cell carcinoma make up 98% of skin cancers.
• Non-melanoma skin cancer is the most common malignant tumour seen in Caucasians. Approximately one million cases were diagnosed in the US in 1999. One out of five Americans will be diagnosed with skin cancer in their lifetime.
  
  

Melanoma

• Melanoma is a highly malignant tumour caused by the mutation of melanocytes in the epidermis.
• It is highly lethal and often metastasises early.
• Like non-melanoma skin cancer, the number of melanoma cases worldwide is rapidly increasing. It is more commonly seen in Caucasians than in Black people.

Characteristics of basal cell carcinoma

• Often appears in head and neck regions which are exposed to sunlight (60%-80%) and the nose (30%).
• Pain, bleeding and blood clot(s) are often observed at the pathological site which does not heal on its own. Itchiness, squamous-like flat scaly clots and painless ulceration are also common.
• Basal cell carcinoma is usually seen as carcinoma-in-situ. It grows along organs with weaker immune defences. It is slow in growing and seldom metastasises, hence treatable if discovered early.
• Carcinoma-in-situ can cause infection, necrosis, pain and irreversible damage to local structures.

Characteristics of squamous cell carcinoma

• 30% of all skin cancers are squamous cell carcinomas.
• Usually arises from skin exposed to strong UV light, skin with previous burn injury, or tissue with slow recovery.
• Typically originates in elderly at sites under sunlight, such as the face, hands and forearms. Most cases are accompanied with rashes, masses and ulceration.
• Squamous cell carcinoma grows slowly, hence it is usually treatable. However, it has to be managed carefully to prevent metastasis.
• Squamous cell carcinoma is more aggressive than basal cell carcinoma. It usually penetrates the basal lamina. Metastasis is commonly going through the lymphatic system to the lymph nodes and less commonly spreading to distant organs like lungs or bones.

Characteristics of melanoma

• Melanoma accounts for around 2% of all skin cancers.
• Commonly presents as a rapidly forming deposit of melanin with ulceration, but can sometimes be amelanotic.
• In Caucasian ladies, 50% of melanomas occur in the legs; in Caucasian gentlemen, most melanomas are found on the trunk. 
• In Asians, melanomas mostly arise in the soles, palms, nail beds or mucosa. 
• Chance of melanoma in the face increases with age. In middle age, it is more commonly observed in other parts of the body. 
• Melanomas can easily spread. Common metastatic sites include local lymph nodes, lungs and brain. Therefore, it is important to diagnose melanomas as early as possible.
• Symptoms of melanoma:
  • New, unusual looking pigmented area on skin 
  • Itchiness, pain and inflammation of the pathogenic site
  • Prolonged unhealed wounds 
  • Growth, transformation or colour change in moles or pigmented area
  • Transformation of moles:
    • Asymmetric shape 
    • Irregular borders
    • Colour change
    • Size above 6mm or observable growth
    • Asymmetric bulging

Biopsy is required to diagnose different types of skin cancer. The doctor will cut out a small area of the suspected site under local anaesthesia. The cells will be sent to the laboratory to identify if the tumour is benign or malignant. The process will take around two weeks.

After getting the diagnosis, doctor will check the exact location, size and degree of metastasis of the skin cancer. Since skin cancer usually grows on the skin surface and the pace of growth is slow with a low chance of metastasis, further investigations may not be required.

The doctor will palpate for any swelling or enlargement of the lymph nodes near the skin cancer. If necessary, further investigations, e.g. blood tests, X-rays, or computed tomography (CT) may be performed.

If malignant melanoma is confirmed, you may need to have more detailed investigatons, e.g. CT scan to check for any distant spread.

Staging for melanoma 

• Stage 0
  • This refers to melanoma in situ, which means melanoma cells are found only in the outer layer of skin or epidermis. 
  • This stage of melanoma is very unlikely to metastasise to other parts of the body.
• Stage I
  • Stage I melanoma will only grow on the skin and is relatively thin. 
  • Stage I is further divided into 2 subgroups, IA or IB, according to the thickness of the melanoma and whether ulceration is seen under a microscope.
• Stage II
  • Stage II melanoma is thicker than stage I melanoma, extending into the epidermis, the dermis and subcutaneous tissues. 
  • It has a higher chance of spreading. 
  • Stage II is further divided into 3 subgroups, A, B, or C, according to the thickness of the melanoma and whether ulceration is seen.
• Stage III
  • Stage III melanoma is one that has metastasised locally, through the lymphatic system to a regional lymph node (near where the cancer started), or to a skin site on the way to a lymph node.
  • Stage III is further divided into 4 subgroups, A, B, C, or D, according to the size and number of lymph nodes involved with melanoma, whether the primary tumour has satellite or in-transit lesions, and if it appears ulcerated under a microscope.
• Stage IV
  • Stage IV melanoma has metastasised through the bloodstream to other parts of the body, such as distant locations on the skin or soft tissue, distant lymph nodes, or other organs like the lung, liver, brain, bone, or gastrointestinal tract. 
  • Stage IV melanoma is further evaluated based on the location of distant metastasis:
    • M1a: The cancer has only spread to distant skin and/or soft-tissue sites.
    • M1b: The cancer has spread to the lung.
    • M1c: The cancer has spread to any other location that does not involve the central nervous system.
    • M1d: The cancer has spread to the central nervous system, including the brain, spinal cord, and/or cerebrospinal fluid, or lining of the brain and/or spinal cord.
• Recurrent
  • Recurrent melanoma is a type of melanoma that comes back after treatment. 
  • The doctor will conduct detailed tests and scans to identify the extent of the recurrence. 

Treatment for skin cancers is mainly by surgery and radiotherapy.

Treatment for basal cell carcinoma

• Majority of basal cell carcinoma can be treated with surgery and radiotherapy.
• The doctor may also recommend other treatment options such as cryotherapy and curettage according to the patient's condition.
• Patients should be followed up in the long run as there is a 5-10% chance of recurrence and metastasis.

Treatment for squamous cell carcinoma

• Majority of squamous cell carcinoma can be treated with surgery and radiotherapy.
• For patients who are either too old or too weak to undergo surgical procedures, radiotherapy is an option.
• Patients are required to be followed up in the long run as there are chances of recurrence and metastasis.

Treatment for melanoma

• Surgery
  • Surgery is the best option for treating melanoma.
  • Patients will require a skin graft when the melanoma is too thick.
  • Some patients need to have some of their lymph nodes removed to prevent metastasis.
  • Patients should be followed up in the long run as there are chances of recurrence and metastasis.
• Interferon
  • Using interferon after surgery decreases the chances of recurrence and increases survival rates.
• Immune checkpoint inhibitors (E.g., Pembrolizumab and Nivolumab)
  • Use of immune checkpoint inhibitors after surgery decreases the chance of recurrence and increases survival rates.

• Most recurrence will spread to other parts of the body. Therefore, the survival rate is low.

Chemotherapy

• For patients who are unfit for surgery to remove the tumour, chemotherapy is possible. 
• However, chemotherapy only poses a moderate effectiveness while posing chances of a number of serious side effects.

Targeted therapy

1. BRAF inhibitors (e.g., Vemurafenib and Dabrafenib)

• 25% of patients with melanoma carry BRAF mutations in Asia. These patients can be treated by BRAF inhibitors Vemurafenib and Dabrafenib which reduce the size of the tumour, slow its growth, and improve survival. It is essential to have genetic test confirming the presence of BRAF mutation before using this group of medications.
• Dosage: Pills or capsules, taken orally, twice a day.
• Common side effects: Skin thickening, rashes, itchiness, photosensitivity, headache, fever, joint pain, fatigue, hair loss and nausea.
• Less common but serious side effects: arrhythmias, liver disease, kidney failure, severe allergic reactions, severe skin problems, eye problems and increase in blood sugar levels. Some patients may develop squamous cell carcinoma after taking the drug, but they are usually milder than melanoma and can be removed surgically.

2. MEK inhibitors (e.g., Trametinib and Cobimetinib)

• MEK gene will combine with BRAF gene to stimulate cancer cells to proliferate. With this mechanism, MEK inhibitors are useful in inhibiting tumour growth in melanoma patients with BRAF mutations.
• MEK inhibitors Trametinib and Cobimetinib are useful in patients with metastatic melanoma with BRAF mutations.
• Dosage: Pills, taken orally, once a day.
• Common side effects: Rashes, nausea, diarrhoea, edema and photosensitivity.
• Less common but serious side effects: Heart damage, massive bleeding, blindness, lung problems and skin infections.
• The combination of MEK inhibitors and BRAF inhibitors are commonly used for patients with metastatic melanoma with BRAF mutation. The combination regimen, compared to a single agent, is more effective and has fewer side effects (such as developing other skin cancers).

3. Immune checkpoint inhibitors

• PD-1 (Programmed Death-1) inhibitors and CTLA-4 (Cytotoxic T Lymphocyte Associated protein -4) inhibitors are immune checkpoint inhibitors which are effective in treating end stage melanoma.
• Pembrolizumab (PD-1 inhibitor), Nivolumab (PD-1 inhibitor), Ipilimumab (CTLA-4 inhibitor) enable white blood cells to recognise and attack cancer cells thereby prolonging the lifespan of melanoma patients.
• Dosage: Intravenously, once per two to three weeks.
• Side effects: Immune checkpoint inhibitors have fewer side effects when compared with older generation drugs. The common side effects are fatigue, coughing, vomiting, rashes, itchiness, constipation, loss of appetite, joint pain and diarrhoea.
• The immune checkpoint inhibitors reactivate the body's self-defence mechanisms to fight cancer cells. However, in rare cases, these drugs might prompt the immune system to attack other normal organs and tissues in the body, e.g., lung, intestine, liver, kidneys and bowel, leading to serious and even fatal side effects. 

Radiotherapy

Radiotherapy can be used to relieve pain and control bleeding in patients with advanced melanoma.

• Studies have shown that 80% of skin cancers can be prevented by protective measures against sunlight.
• Protective measures should start early as 80% of damage by ultraviolet rays is done before the age of 18.

• Children under one year old should not sunbathe directly.
• Do not conduct indoor tanning.
• Avoid outdoor activities from 11am to 3pm as ultraviolet rays are most damaging during this period. Persons with pale complexions might get sunburnt in less than 15 minutes at noon.
• Wear protective clothing such as long-sleeved shirts, trousers and wide-brimmed hats when participating in outdoor activities. Wear sunglasses when necessary.
• Apply sunscreen with sun protection factor (SPF) of at least 15 and PA++ to exposed skin when participating in outdoor activities to protect the skin from UVA and UVB.
  • SPF refers to the ability of a sunscreen to protect the skin from UVB. The higher the number, the better the protection.
  • SPF = Time required for skin to turn red from UVB after applying sunscreen/Time required for skin to turn red from UVB without applying sunscreen.
  • Sunscreen with SPF15 can block 93% of UVB, while sunscreen with SPF30 can block 97% of UVB.
  • PA refers to the ability of a sunscreen to protect our skin from UVA. The greater number of ‘+’, the better the protection.
  • Tips for applying sunscreen
    • One teaspoon of sunscreen is required for the face while 30mL of sunscreen is required for the whole body.
    • Use sufficient sunscreen with SPF 15/30, rather than a thin layer of sunscreen with SPF 60/100.
    • Apply sunscreen 30 minutes before outdoor activities.
    • Apply sunscreen when swimming outdoors.
    • Reapply sunscreen every 2 hours when staying outdoors for a long period of time.
    • Reapply sunscreen after swimming or sweating.
    • Seek shade whenever possible even with sunscreen applied.
      

The Hong Kong Anti-Cancer Society: Skin cancer (Chinese only)

Smart Patient (by Hospital Authority): Skin cancer

American Society of Clinical Oncology (ASCO): non-melanoma skin cancer

Canadian Cancer Society: non-melanoma skin cancer

Special thanks to Ms. Locani Hing-Wai Wong (Class M25), Mr. Alex Yung-Pok Lee (Class M25), medical student of Li Ka Shing Faculty of Medicine, the University of Hong Kong, and Dr. Wendy Wing-Lok Chan, Department of Clinical Oncology, the University of Hong Kong for authoring and editing this article.

Last updated on 18th Dec, 2023.