Buccal Mucosa Cancer: Symptoms, Types, Causes and Treatment

Buccal mucosa cancer is a form of oral cancer that affects the inner lining of the cheeks. While relatively rare in some regions, it is among the most common types of oral cavity cancers in South Asia and other high-risk populations. This cancer is notable for its aggressive behavior, frequent late-stage diagnosis, and strong association with preventable lifestyle factors. Understanding its symptoms, types, causes, and treatments is crucial for early detection and improved outcomes.

Symptoms of Buccal Mucosa Cancer

Recognizing the early signs and symptoms of buccal mucosa cancer can make a significant difference in the success of treatment and overall survival. Unfortunately, many cases are only diagnosed once the disease has reached an advanced stage, especially in populations with limited awareness and access to healthcare. Both patients and healthcare providers need to be vigilant about the subtle and more overt symptoms.

Symptom	Description	Frequency/Significance	Source(s)
Pain	Persistent pain in the cheek/mouth	Common initial complaint	1, 2
Bleeding	Unexplained bleeding from the mouth	Often occurs in late stages	1
Swelling	Lump or thickening in cheek	May restrict movement	2, 3
Limited opening	Difficulty opening mouth (trismus)	Post-surgical or late sign	2

Table 1: Key Symptoms

Pain and Discomfort

Pain is the most frequently reported symptom, often prompting patients to seek medical attention. This pain may start as mild discomfort but can progress to severe, persistent pain as the tumor grows or invades surrounding tissue. In some cases, pain might radiate to the jaw or ear, particularly in advanced disease 1, 2.

Bleeding and Ulceration

Unexplained bleeding is another common sign, especially when the tumor ulcerates or erodes blood vessels in the cheek lining. Patients might notice blood in their saliva or when brushing their teeth. Sometimes, a persistent sore or ulcer on the inside of the cheek fails to heal, which should always raise suspicion 1.

Swelling and Restricted Movement

Swelling or a noticeable lump in the cheek is a key warning sign. As the tumor enlarges, it may cause visible or palpable masses. Swelling can also restrict jaw movement, leading to trismus (difficulty opening the mouth), which is especially noticeable after surgical interventions or in advanced disease 2, 3.

Other Symptoms

Additional symptoms may include:

• Numbness of the cheek or lower face
• Difficulty chewing or swallowing
• Change in voice or speech
• Weight loss in advanced cases

It is important to note that these symptoms can sometimes be mistaken for more benign conditions, further contributing to delays in diagnosis 1, 2.

Types of Buccal Mucosa Cancer

Buccal mucosa cancer is not a single entity; rather, it encompasses various subtypes, each with distinct clinical and pathological characteristics. Understanding these types helps guide treatment and predict outcomes.

Type	Description	Prevalence/Notes	Source(s)
Squamous Cell Carcinoma (SCC)	Cancer from squamous epithelial cells	Most common (>90%)	1, 3, 4, 6
Well-differentiated	Tumor cells resemble normal cells	~50% of SCC cases	1
Moderately-differentiated	Intermediate resemblance to normal cells	~34% of SCC cases	1
Poorly-differentiated	Cells look very abnormal, aggressive	~16% of SCC cases	1
Non-SCC	Includes rare adenocarcinomas, lymphomas	Very rare	9

Table 2: Types of Buccal Mucosa Cancer

Squamous Cell Carcinoma: The Dominant Type

Squamous cell carcinoma (SCC) accounts for the vast majority of buccal mucosa cancers. SCC arises from the squamous epithelial cells that line the inside of the cheeks. It is known for its aggressive nature and high potential for local recurrence and regional spread 1, 3, 4.

Variants by Differentiation

• Well-differentiated SCC: These tumors closely resemble normal squamous cells and tend to grow more slowly. They are the most common, making up about half of all cases 1.
• Moderately-differentiated SCC: These have features between well and poorly differentiated types and account for about one-third of cases 1.
• Poorly-differentiated SCC: These aggressive tumors show high-grade cellular abnormalities and often indicate a worse prognosis 1, 6.

Non-Squamous Cell Cancers

Although exceedingly rare, other cancer types can arise from the buccal mucosa, including adenocarcinomas and lymphomas. There are also cases in individuals with no traditional risk factors, suggesting that genetic and molecular pathways can play a role in non-tobacco related cancers 9.

Special Considerations: Young Adults and High-Risk Groups

While buccal mucosa cancer is more prevalent among older adults, there are documented cases in young adults, especially those with significant tobacco or areca nut exposure. These cancers may behave more aggressively and are often diagnosed at an advanced stage 4.

Causes of Buccal Mucosa Cancer

The development of buccal mucosa cancer is influenced by a complex interplay of lifestyle, environmental, genetic, and sometimes viral factors. Understanding these causes is essential for both prevention and early intervention.

Cause	Mechanism/Details	Risk Magnitude/Notes	Source(s)
Tobacco chewing	Direct carcinogen exposure to cheek mucosa	Major cause (esp. in Asia)	4, 8, 9
Smoking	Inhaled carcinogens affect oral mucosa	Strong association	4, 8
Betel quid/Areca nut	Chewed with/without tobacco	Significant risk factor	8, 10
Alcohol	Synergistic effect with tobacco	Increases overall risk	4, 8
Low socioeconomic status	Associated with higher risk behaviors	Linked to late presentation	8
Genetic mutations	Tumor suppressor and oncogene alterations	Found in non-users too	9, 10
Oral potentially malignant disorders (OPMDs)	Pre-cancerous lesions (e.g., leukoplakia, OSMF)	High risk of transformation	10
HPV and viruses	Possible but less common in buccal cancer	Under investigation	10

Table 3: Major Causes and Risk Factors

Lifestyle and Environmental Factors

Tobacco in All Forms

Tobacco use, especially chewing tobacco, is the single most significant risk factor for buccal mucosa cancer. In regions like India, Pakistan, and other parts of Asia, the habit of placing tobacco or betel quid inside the cheek for prolonged periods exposes the mucosa to carcinogens, dramatically increasing cancer risk 4, 8. Smoking further compounds this risk.

Betel Quid and Areca Nut

Betel quid, often mixed with areca nut and sometimes tobacco, is another potent carcinogen. The habit is prevalent in South Asia and among migrant communities worldwide. Chewing these substances leads to chronic irritation and DNA damage in the cheek lining 8, 10.

Alcohol Consumption

Alcohol acts synergistically with tobacco, multiplying the risk of oral cancers by facilitating the entry of carcinogens and impairing cellular repair mechanisms 4, 8.

Socioeconomic and Demographic Factors

Low socioeconomic status is closely linked to higher rates of tobacco and betel quid use, poor oral hygiene, and delayed healthcare access. These factors contribute to both increased incidence and more advanced stage at diagnosis 8.

Genetic and Molecular Pathways

Not all cases are linked to lifestyle factors. Some patients, notably those who have never used tobacco or alcohol, develop buccal mucosa cancer due to genetic mutations in tumor suppressor genes (like TP53, CDKN2A) and oncogenes (such as MYC, EGFR) 9, 10. These cases underscore the role of hereditary factors and spontaneous genetic changes.

Oral Potentially Malignant Disorders (OPMDs)

Conditions such as oral leukoplakia, erythroplakia, and oral submucous fibrosis (OSMF) are considered pre-cancerous. They represent a high-risk state where the cheek lining is already undergoing changes that may progress to cancer, especially in the presence of ongoing risk factors 10.

Viral Infections

While viruses like HPV are established causes in some head and neck cancers, their role in buccal mucosa cancer is still being explored and appears less pronounced than for other sites 10.

Treatment of Buccal Mucosa Cancer

Treatment for buccal mucosa cancer is determined by the stage of the disease, type of tumor, patient’s overall health, and available resources. A multimodal approach—often combining surgery, radiotherapy, and chemotherapy—is common, especially for advanced or aggressive tumors.

Treatment	Description/When Used	Key Outcomes/Notes	Source(s)
Surgery	Removal of tumor and margin of healthy tissue	Mainstay for early and resectable cases	1, 5, 6
Radiotherapy	External beam or brachytherapy	Used for early cases, adjuvant, or inoperable cases	11, 12
Chemotherapy	Systemic drugs (often with radiotherapy)	For advanced/metastatic disease	1, 6, 13
Multimodal	Combination of above	Improves local control/survival	6, 12, 13
Physiotherapy	Post-operative rehabilitation	Reduces morbidity, improves function	2

Table 4: Treatment Modalities

Surgery: The Cornerstone

Surgical excision remains the primary and most effective treatment for buccal mucosa cancer, especially in early-stage disease. The goal is to remove the tumor along with a margin of healthy tissue to minimize the risk of local recurrence. However, even with negative margins, recurrence rates remain high, underscoring the aggressive biology of this cancer 1, 5, 6.

• Early-stage disease: Surgery alone may suffice but careful monitoring is required.
• Advanced disease: Surgery may be combined with reconstruction and lymph node dissection 1.

Radiotherapy

Radiotherapy can be used as:

• Primary treatment: For patients unfit for surgery or those with early-stage disease.
• Adjuvant therapy: After surgery, especially in cases with close/positive margins, large tumors, or lymph node involvement 11, 12.
• Palliative care: To relieve symptoms in advanced, non-curable cases.

Post-operative radiotherapy has been shown to significantly improve disease-free survival, especially in stage III/IV cancers 12.

Chemotherapy

Chemotherapy is often used in combination with radiotherapy (chemoradiation) for:

• Unresectable or inoperable tumors
• Advanced-stage disease
• As an adjunct to surgery and radiotherapy to improve outcomes 1, 6, 13

Common agents include cisplatin and 5-fluorouracil, but resistance can occur, especially in aggressive or poorly differentiated tumors 9.

Multimodal Therapy

Given the aggressive nature and high recurrence rates of buccal mucosa cancer, a combination of surgery, radiotherapy, and chemotherapy is frequently employed. Studies highlight that even early-stage tumors may benefit from adjuvant therapy to prevent recurrence 5, 6, 13.

Supportive and Rehabilitative Care

Post-surgical complications such as restricted mouth opening (trismus), pain, swelling, and impaired chewing are common. Physiotherapy and supportive care are crucial to restore function and improve quality of life 2.

Prognosis and Outcomes

• Early detection: Dramatically improves survival; 5-year survival for stage I/II can be over 80% 6, 11.
• Late-stage disease: Prognosis declines sharply, with 5-year survival dropping to less than 50% in stage III/IV 6.
• Recurrence: Remains a major challenge, even with negative surgical margins 5.

Conclusion

Buccal mucosa cancer is a serious health issue, particularly in regions and communities where tobacco, betel quid, and areca nut chewing are prevalent. Early symptoms are often subtle, leading to late diagnoses and poorer outcomes. However, with increased awareness, early detection, and a multidisciplinary approach to treatment, survival rates can be improved.

Key Takeaways:

• Buccal mucosa cancer most commonly presents with pain, swelling, and non-healing ulcers or bleeding inside the cheek 1, 2.
• The overwhelming majority of cases are squamous cell carcinomas, with varying degrees of aggressiveness 1, 3, 6.
• Major risk factors include tobacco chewing, betel quid/areca nut use, smoking, and alcohol; genetics and pre-cancerous lesions also play significant roles 4, 8, 9, 10.
• Treatment typically involves surgery, often in combination with radiotherapy and chemotherapy, especially for advanced cancers 6, 12, 13.
• Early detection and prevention—through lifestyle changes and regular oral health checks—are critical to improving outcomes.

By empowering individuals and healthcare professionals with knowledge, we can reduce the burden of buccal mucosa cancer and give patients a better chance at early diagnosis and successful treatment.