Squamous Cell Carcinoma Explained:
Squamous Cell Carcinoma (SCC) is the second most common skin cancer and an overwhelming malignancy of a vast amount of mucosal and epithelial tissue in the whole body. SCC develops in squamous cells, flat scale-shaped cells on the skin surface and organ lining. SCC occurs in a very wide variety of forms that can be very mild to very violent in character; if not treated, there is always a chance of metastasis, and the cancer cells spread to other parts of the body.
What you will get here:
- SCC introduction, symptoms, risk factors, and overall methods of treatment.
- Definition of keratinizing SCC, in which the keratin is formed and can have disorganized growth.
- Definition of oral SCC, that occurs on the mucous lining of the mouth and presents certain special clinical challenges to be tackled.
- Definition of well-differentiated SCC, in which the SCC cells are like normal cells and slow-growing.
- A description of SCC of the tongue, with particular emphasis on its usual features and how these affect treatment.
- A reference to moderately differentiated SCC, intermediate between well-differentiated and poorly differentiated in cell appearance and malignancy.
What is Squamous Cell Carcinoma?
Squamous Cell Carcinoma (SCC) is caused by squamous epithelial cells, which are flat cells covering the outer layer of the skin as well as most organs of the human body, e.g., the digestive tract and respiratory tracts. Though SCC does indeed manifest primarily with skin cancer, it does manifest itself in many other locations throughout the body as well, including in the lungs, esophagus, cervix, and within the mouth. SCC may occur in one of many various different forms depending upon where its origination is found and is further accompanied by an equally vast amount of signs and symptoms of treatment and complications as well. Causes and Risk Factors
The causes of the formation of SCC are as follows:
- Long-term exposure to sun or tanning bed
- HPV infection, the most common of which are HPV-16 and HPV-18 (oral SCC and genital SCC)
- Smoking and alcohol use
- Immunosuppression
- Chronic inflammatory cutaneous condition or wound
- Carcinogen exposure (e.g., arsenic, industrial toxics)
Squamous Cell Carcinoma Symptoms
Signs and symptoms of squamous cell carcinoma (SCC) depend on its location, but some of its signs to watch for are:
- Rough or scaly skin patch that is not healing with the passage of time, demonstrating a persistent and annoying change.
- Red hard and elevated bump visible above the skin.
- Crusting, bleeding, or non-healing of an open sore, i.e., the sore does not heal.
- Red or white mucosal mouth lesions, which can be oral squamous cell carcinoma and one should be cautious of.
- Dysphagia or hoarse voice not improving, especially in esophageal squamous cell carcinoma, i.e., something is wrong in the throat region.
Treatment of Squamous Cell Carcinoma
1. Surgical Excision: The most common treatment of localized SCC is surgical removal. Surgical removal is resection and removal of the tumor along with a border of normal tissue around the tumor. The border is to decrease recurrence of cancer by removing microscopic cancer cells within the border tissue.
2. Mohs Micrographic Surgery: Mohs micrographic surgery is most valuable in facial squamous cell carcinoma surgery or recurrence of a tumor after prior treatment.
Slow, gradual removal of the cancerous tissue layer by layer is done in this complex operation. Microscopic examination of the tissue after removal of each layer to ensure that there are no cancer cells left behind is performed. This exercise is repeated again and again until the physician feels assured that there are no additional cancer cells and that makes it a legitimate practice of achieving clean margins.
3. Radiation Therapy: Radiotherapy is most frequently preferred as an accepted alternative to surgery if discovered not to be suitable, or adjuvant therapy given in addition to surgical treatment. The treatment is best employed on large tumours or tumours already formed in proximal lymph nodes. With its action of exposing the tumour cells to high-dose radiation, the treatment aims to reduce tumours and kill malignancies with minimal damage to the health tissue surrounding.
4. Topical Medications: Apart from surgery, superficial squamous cell carcinomas can be treated without surgery in the form of topical medications. Topical medications such as 5-fluorouracil (5-FU) or imiquimod are applied topically on the skin in a local manner, where they act at the cellular level destroying the cancer cells, providing an alternative that is less invasive for patients.
5. Photodynamic Therapy: Photodynamic therapy is a new form of treatment involving the administration of a photosensitizing drug into the skin. The drug becomes trapped inside the cancer cells, and the cells become light-sensitive. After application of the agent to the skin, the skin is exposed to a known wavelength of light, which will subsequently go on to interact with the photosensitizer to cause death in the superficially positioned SCC cells without causing damage to the inner skin layers.
6. Systemic Therapies: In metastatic squamous cell cancers, having relinquished their original position, systemic treatment comes in within the management. These usually involve targeted therapy as drugs such as cetuximab, targeting specific pathways down which cancer cells move, or immunotherapies such as PD-1 inhibitors (such as pembrolizumab or cemiplimab), which encourage the immune system of the body to kill off the cancer cells. They introduce the hope of increased disease, with expectation of increased survival and outcomes.
A 2020 New England Journal of Medicine trial reported cemiplimab with an overall response rate of 50% in advanced cutaneous SCC patients, whose efficacy was reported when given as a systemic treatment.
Keratinizing Squamous Cell Carcinoma
Normal keratin-like secretion of keratin by cancer cells is typical of keratinizing SCC. It is more probable to take place on sites such as skin, lungs, or cervix.
Features
- Extremely histologically differentiated
- Production of keratin pearls (rings of keratin in concentric fashion)
- Typically slower growing than non-keratinizing forms
Clinical Implications:
Although still metastasizing, keratinizing SCC is less malignant than non-keratinizing forms. Overall, the tumor can typically respond well to irradiation and surgery. Keratinization has been found to be linked with good prognosis in head and neck SCCs because of increased levels of differentiation, as per a 2022 meta-analysis in Frontiers in Oncology.
Oral Squamous Cell Carcinoma (OSCC)
Oral SCC is responsible for more than 90% of oral cancers and occurs most frequently on the tongue, floor of the mouth, buccal mucosa, and lips.
Risk Factors:
- Smoking and smokeless tobacco
- Alcohol
- HPV infection
- Poor oral hygiene
- Betel nut chewing (most prevalent in Southeast Asia)
Symptoms:
- Not healing mouth ulcers
- Painful or swallowing difficulty
- Red or white patches in mouth
- Swelling or lump on the jaw or neck
Treatment:
- Surgery is usually the initial form of treatment.
- Chemoradiation and chemotherapy are increasingly utilized with advanced stages.
- Targeted therapy and immunotherapy increasingly create a metastatic disease management.
A 2021 publication in The Lancet Oncology described the increasingly central role of HPV-positive OSCC, which is extremely curable and carries a superior survival prognosis compared to HPV-negative cancers.
Well Differentiated Squamous Cell Carcinoma
Well-differentiated SCC is a slowly growing neoplasm with neoplastic cells having normal squamous architecture and appearing in well-differentiated structures.
Histological Features:
- Increased formation of keratin
- Goodly developed cell structure
- Reduced rate of growth and reduced metastatic potential
Prognosis:
The prognosis is good in the majority of cases, especially with early diagnosis. Treatment is complete excision with or without irradiation.
Squamous Cell Carcinoma of the Tongue
It is the most common oral cavity cancer, found in most instances in men over 50 years. The ventral tongue surface and the lateral margins are the most common sites.
Etiology:
- Tobacco and alcohol
- HPV (most commonly HPV-16)
- Chronic mechanical irritation (e.g., ill-fitting dentures)
- Genetic mutations (p53, EGFR overexpression)
Symptoms:
- Painful tongue lesion
- Bleeding ulcer
- Difficulty in speech or swallowing
- Swollen lymph nodes
Diagnosis:
- Biopsy for histopathological diagnosis.
- Imaging such as MRI or CT scans to determine tumor depth and nodal disease.
Treatment:
- Early-stage: surgery alone or in combination.
- Advanced stage: surgery, radiotherapy, and chemotherapy.
Targeted therapy with EGFR inhibitors or immunotherapy in recurrent/metastatic disease.
Moderately Differentiated Squamous Cell Carcinoma
It is a middle category of well-differentiated and poor differentiated SCC. It has:
- Some keratinization
- Middle cell atypia
- Mid mitotic activity
- Clinical Behavior
More virulent than well-differentiated SCC but less than poor differentiated ones. Tends to develop in middle or late stages, particularly in head and neck, esophagus, or cervix.
Treatment:
- Usually requires multimodal management: surgery, radiation, and possibly chemotherapy.
- Carefully follows because of heightened risk of recurrence.
Prognosis and Survival Rates
SCC prognosis is based on a few elements:
- Origin: Cutaneous SCC has a better prognosis than oral or esophageal SCC.
- Degree of differentiation: Well-differentiated > poorly differentiated.
- Metastasis: Regional lymph node metastases worsen prognosis.
- HPV status: HPV status cancers, especially oropharynx cancers, are curable.
Survival Rates (Approximate 5-Year Data):
- Cutaneous SCC (non-metastatic): 95%
- Oral SCC (early stage): 70-80%
- Oral SCC (advanced stage): 30-50%
- SCC of the tongue: 50-60% (stage-dependent)
Prevention and Early Detection
Although SCC has potential aggressiveness, early detection absolutely flips prognosis. Prevention is as follows:
- Avoid sun and apply sunscreens
- Avoid smoking and not drinking alcohol
- HPV vaccine (certainly for cervical and oropharyngeal SCC)
- Routine dental checkup to identify oral lesions in the early stage
- Biopsy of any abnormal cutaneous or mucosal lesion
Sum up,
Squamous Cell Carcinoma is an aggressive but not rare cancer that can strike many different areas of the body. Accurate grading, quick intervention, and accurate diagnosis are all the keys to best survival and health. From keratinizing to moderately differentiated, particularly in high-risk locations like the tongue and oral cavity, patient and physician education on pathology and treatment of highest concern. As targeted therapy as well as immunotherapy have advanced, late SCC now holds a new hope for survival. Stay alert. Screen yourself. Stay alert to your skin and your own health.
