Introduction

Oral cancer ranks as the 13^th most prevalent type of cancer with 377,713 new cases and 177,757 deaths worldwide in 2020.¹ In Europe, an estimated 100,000 people are being diagnosed with oral cancer annually, with worldwide trends continue growing.² Despite oral cancers being highly preventable given the potential of limiting the primary risk factors, late detection contributes to high mortality rates, with 5-year survival rates at around 40%. In high-risk areas, such as South, and Southeast Asia, and the Western Pacific islands, oral cancer accounts for 25% of all new cancer cases.^3­  This cancer predominantly affects middle-aged people assigned male at birth, with double the incidence compared to those assigned female at birth. However, a rising trend is detectable among younger individuals, according to the latest epidemiologic studies.⁴ 

In 90% of cases, mouth cancers occur as squamous cell carcinomas (OSCC), this includes cancers in the lips and oral cavity, including the tongue, gums, floor of mouth, palate, and other areas.⁵ Early diagnosis is pivotal for the best prognosis, yet the initial stages are often characterised by symptoms that resemble other conditions or remain asymptomatic. The lack of clear indicators minimises the likelihood of prompt medical intervention, exacerbating cancer progression.⁴

A more in-depth examination of oral cancer stages proves beneficial in understanding its progression trajectory and impact on prognosis.

Overview of oral cancer

Types of oral cancer

Oral cancer can manifest in different regions of the mouth and lips presenting unusual lumps, spots, or ulcers. OSCC is the predominant form, which arises on the mucosal epithelium of the oral cavity. However, other rarer types have also been recognised, including:⁶

• Minor salivary gland tumours
• Basal cell carcinomas
• Melanomas
• Lymphomas
• Sarcomas

Risk factors

Certain damaged tissue within the oral cavity may emerge before the onset of cancerous growths, designated as precancerous.³ Furthermore, distinct risk factors have been identified, influencing the occurrence and progression of oral cancer, including:⁷

1. Tobacco consumption: carcinogens in tobacco smoke may induce DNA damage. 
2. Betel quid chewing: it involves a mixture of betel leaf, slaked lime, areca nut, and tobacco. It is a famous habit in Southeast Asia and is strongly implicated in oral cancer occurrence.
3. Alcohol: its synergistic action with tobacco has been linked to leukoplakia and oral dysplasias.
4. Viral infections: viruses such as Epstein-Barr, human papillomavirus, and herpes simplex may contribute to the development of oral cancers.
5. Dental health: oral hygiene and dental condition play significant roles in overall oral health.

Stages of oral cancer

Many environmental and familial factors could influence the progression of malignant transformation in the oral cavity. Cancerous growths progress through various stages, exhibiting varying symptomatology and severity, significantly impacting the prognosis of the disease.

Stage 0: carcinoma in situ

At this initial stage, oral cancer is characterised by the presence of abnormal cells within a specific lining of the oral cavity. These precancerous cells have not yet spread to nearby tissues, but if left untreated, they can become malignant and invasive.⁸

Detecting oral cancer at this early stage is of major significance, as it directly correlates with increased patient survival rates. However, early diagnosis is a rather challenging task; the potential asymptomatic state of individuals at this stage, or a patient not seeking healthcare assistance promptly, can impede timely specialised examination.⁹

Stage I: early localised

The initial stage I of oral cancer refers to primary tumours that are either less than or equal to 2 cm and 5 mm deep. They have not invaded surrounding tissues, regional lymph nodes, or other organs, although they may be indications of the initiation of metastasis.⁸

Diagnosis at this early stage remains complex, as only one-third of OSCC patients are typically diagnosed at stages I or II. Therapeutic options greatly depend on the stage of oral cancer, which also impacts the prognosis and survival rates of patients. Notably, stage I diagnosis holds a relatively favourable prognosis, with treatment success rates reaching 80%.¹⁰ Additionally, the identification of specific salivary biomarkers in patients at early stages allows for precise stage diagnosis, contributing to accurate therapeutic and prognostic outcomes.¹¹

Stage II: advanced localised

In stage II oral cancer, malignant tumours remain localised without spreading to surrounding lymph nodes or other organs. The tumour size may exceed 2cm but be less than 4cm, it could also be less than 2 cm in size but be deeper than 5 mm, up to 10 mm.⁸

Diagnosis in this stage, frequently manifesting with minor lumps, may involve computed tomography (CT) scans.¹² Generally, the 5-year survival rate at this stage is reduced compared to stage I, with cure rates at 65%.¹⁰ For instance, stage II OSCC presents a survival rate of 70%.⁵ Radiotherapy and surgery stand as the recommended approaches for coping with the early stages of mouth cancer.¹²

Stage III: regional spread

Stage III of oral cancer corresponds to a more advanced form of malignant growths, where:^8,10

• The tumour may be of any size but has invaded one lymph node in the neck or on the same side where cancer cells are located, with the lymph node being 3 cm or smaller.
• The tumour is greater than 4 cm in dimension but has not spread to regional lymph nodes or other organs.

Approximately 60% of mouth cancers are detected in stages III and IV, lowering treatment and survival rates.⁹ This is clear from the 5-year survival rate of OSCC, which is approximately 57.6%.⁵ Advanced stages demonstrate more pronounced symptoms, such as pain, bleeding, or the presence of a mass in the mouth or neck.³ Treatment options are carefully examined based on the clinical image and the stage of malignancies, taking into account the state of the tumour and how much it has spread.¹⁰

Stage IV: advanced and metastatic

This stage involves the most advanced cases of oral cancer and is further subdivided into three sub-stages:^8,10

• Stage IV A:
  • The tumour has invaded nearby tissues, penetrating cortical bones into the tongue, sinus, or skin of the face. Metastasis may or may not be present in one lymph node.
  • The tumour can be of any size and has metastasised in one or more lymph nodes of any site of the neck, with dimensions between 3-6 cm.
• Stage IV B:
  • The tumour could be of any dimension and has metastasised in one lymph node with a dimension greater than 6 cm.
  • The tumour has advanced local invasion of the nearby masticator space, skull base, or carotid arteries and has also invaded one or more lymph nodes with any dimension.
• Stage IV C: the tumour has any dimension and has either moderately or advanced invaded local tissues, has metastasised in one or more lymph nodes with any dimension, and distant metastasis is also present, indicating spread to other parts of the body

In this late-stage of oral cancer treatment rates are lower, and the likelihood of survival is drastically reduced, with the 5-year survival rate for OSCC ranging around 53.9% or less and a treatment rate at 30%.^5,10

Diagnostic methods

Early diagnosis is paramount, augmenting the need for swift, non-invasive methods for the identification of oral cancer. An initial physical examination is conducted, along with staining methods and histopathological examination, followed by further specific diagnostic tests, including:¹²

1. Biopsy: different biopsy techniques, such as brush and incisional biopsies, expedite highly specific cancer screenings.
2. Imaging techniques: magnetic resonance imaging (MRI), CT, and positron emission tomography (PET), among others, are performed to assess the spread of oral cancer.
3. Spectroscopy: laser-induced tissue autofluorescence is one of the many optical techniques employed to evaluate the grade of cancer metastasis.
4. Biomarker detection: specific biomarkers are linked with the development of cancer cells and the progression of oral cancer.

Treatment types

The site and size of the initial tumour are critical factors for selecting the various treatment options for oral cancer. Additionally, a patient’s age, lifestyle, and overall health all include significant considerations for tailoring therapeutic strategies. Common interventions for the management of oral cancer include:¹³

1. Surgery

The most prevalent treatment option aims to completely remove the malignant growth, preventing its progression and metastasis. Surgical procedures include neck dissection, debulking surgery, piezosurgery, mandibulectomy, and laser or robotic surgery. 

2. Radiotherapy

Often used in combination with other therapies, this method incorporates high-energy photons to eliminate cancer cells by causing DNA damage.

3. Chemotherapy

This method is often utilised alongside radiotherapy, especially in advanced-stage oral cancer. Numerous chemotherapeutic drugs are used to kill cancer cells but come with diverse side effects.

4. Targeted therapy

This method uses specific drugs capable of targeting and killing cancer cells without affecting healthy cells.

5. Immunotherapy

This technique does not directly target cancer cells but focuses on boosting the body’s immune system to fight cancer.

Conclusion

In summary, oral cancer encompasses malignancies of the lips and oral cavity and predominately manifests as OSCC. While not among the most common cancers globally, epidemiological data underscore poor prognoses, primarily attributed to late diagnoses. Socioeconomic factors and ignorance among both patients and healthcare providers result in low survival rates, as the majority of oral cancers are detected in late stages. Habits such as tobacco smoking, alcohol consumption, and areca chewing, particularly observed in South and Southeast Asia, and the Western Pacific Islands, are the main risk factors increasing the risk of developing oral cancer.

The stages of oral cancer play an indispensable role in determining treatment success and prognosis. Patients seeking medical assistance at early stages exhibit higher survival rates than those in stages III or IV. While the initial symptoms might not be specific, it is crucial to maintain good oral hygiene with regular dental visits. If you notice unusual sores, patches, lumps, or rough spots at any part of your mouth, seeking professional assistance is advised. Enhancing public and professional awareness is a potent tool in improving prognostic outcomes for this potentially life-threatening condition.