Introduction

Normal healthy cells have control mechanisms, governed by genes, that limit the growth and multiplication of cells. However, when changes in these genes (called mutations) occur, cells gain the ability to ignore instructions on when to start and stop growing and dividing, and this leads to the formation of cancer. Cancers of the lips account for more than one-fourth of oral cancers and are the second most common type of skin cancer that occurs in the head and neck region of the body, although it only makes up around 1% of all cancer diagnoses.¹ Lip cancers commonly involve the lower lip and occur in men more than in women.¹ More than 90% of all lip cancers are squamous cell cancers, and more rarely, they can be basal cell cancers or melanomas. Tobacco smoking, excessive alcohol consumption, ultraviolet radiation, trauma, infections with Epstein-Barr virus, human papilloma virus, and a weakened immune system are known risk factors for the development of cancers of the lips.² 

Clinical examination, radiological assessment, biopsy, and histological correlation form the cornerstone for diagnosing lip cancers. Early diagnosis of the condition is extremely important to start appropriate treatment as soon as possible to improve the overall outcome of the individual.³

Physical examination

A thorough physical examination can identify lesions suspicious of cancer and is considered the initial step in the diagnosis of cancers of the lips. Lip cancers in the early stages commonly appear as mouth sores and can be mistaken for cold sores. However, unlike benign cold sores, these would not go away in one to two weeks but persist for longer durations. There can be red or white patches, thickened areas or small ulcers. Meanwhile, late stages can present as larger crusted growths with bleeding and enlarged palpable lymph nodes in the neck.¹ 

Often, lip cancer is detected during a routine oral examination. When a doctor or a dentist suspects lip cancer, they would perform a more detailed examination of the oral cavity. Inspection of lips, tongue, teeth, gums, palate, and floor of the mouth will be carried out to identify lesions such as sores, lumps, changes in colour, and bleeding spots. Next, the walls and floor will be palpated from the inside and outside to identify any swellings. They will also check whether lymph nodes are enlarged in the neck, which could indicate the spread of cancer in late stages.⁴

Biopsy 

If a lesion suspicious for cancer is identified during the examination, the healthcare provider will recommend a biopsy. A small piece of tissue from the lesion is removed, which is seen under the microscope by pathologists to detect the presence of cancer cells. This will also give information about the type of cancer and how aggressive it is. 

During the procedure, the suspicious tissue area will be numbed with an anaesthetic agent. A small incision will be made in the area that needs to be examined using a scalpel, and a small piece of tissue will be removed. Stitches may be applied to close the wound. Possible complications include bleeding, infection, pain, swelling, and damage to adjacent structures such as the teeth, gums, etc.⁵

If enlarged lymph nodes are present, they might perform another test called fine needle aspiration cytology (FNAC) where the contents of the lymph node are taken out. Using ultrasound guidance, a thin needle will be used to aspirate the material inside the lymph nodes that are suspected to have cancer cells. This material, when examined under the microscope, will show the presence of cancer cells.⁶

Imaging studies

Once a biopsy confirms the presence of cancer, the next step would be to perform imaging to detect the spread of the disease to surrounding bone, lymph nodes and distant organs like the lungs. Detecting the spread of cancer aids in staging, which is important in planning out treatment. 

Common imaging techniques utilised include:

• Jaw radiography (pantomography): This captures a wide-angle view of the mouth and can be used as the primary tool to detect invasion of bone by cancer
• Computed Tomography (CT): CT scans give information regarding size and other characteristics of the cancer, depth of invasion and involvement of adjacent bones, and lymph node spread⁷
• Magnetic Resonance Imaging (MRI): MRI scans give details about very small lesions and are especially important to assess the spread of cancer into the surrounding soft tissues, such as the muscles and nerves. These scans are helpful for doctors in deciding the scope and type of surgery that needs to be performed and evaluating complications that can occur during and after surgery⁷
• Positron Emission Tomography (PET) scan: PET scans can detect increased metabolic activity of cancer cells and thereby assess the spread of cancer to lymph nodes and distant sites. They are used in deciding and planning non-surgical treatment options like radiation and chemotherapy, and predicting the risk of recurrence⁷

Integration of diagnostic tools

Physical examination, biopsy and pathological examination, and imaging studies play complementary roles in the diagnosis of lip cancers. A single component can indicate the presence of cancer; however, to detect and confirm the cancer early and accurately stage and monitor it, the integration of results from all the components is important.

Future directions

As science evolves, the diagnosis of lip cancers is expected to change in the next few decades. Saliva is being studied as a source of liquid biopsy, where circulating DNA released from cancer cells can be detected and tested. In addition, artificial intelligence models based on deep learning are providing promising approaches for the analysis of saliva to detect cancer biomarkers. The advances in genetics are helping to identify mutated genes themselves for risk stratification and early identification of cancer.⁸

Frequently asked questions

What is a cold sore?

A cold sore is a fluid-filled blister that appears on the lips or mouth, which can be quite painful. They are due to an infection by a virus called the Herpes Simplex Virus (HSV). They can spread fast through sharing utensils, kissing, or coming into contact with infected saliva.

Can cold sores turn into lip cancer?

Cold sores are considered harmless. Although lip cancers can look like cold sores sometimes, cold sores do not turn into lip cancers.

How is lip cancer treated?

The first step in managing lip cancer is surgery. Radiation, chemotherapy and other targeted treatment options are used according to the characteristics of the tumour.

Can lip cancer be cured?

Lip cancers generally have a good prognosis if detected and treated early in the disease. Almost 90% of individuals with lip cancer become disease-free after treatment. However, the presence of a larger lesion, invasion of surrounding tissue and spread to distant sites can worsen the prognosis. 

How can lip cancer be prevented?

The occurrence of lip cancer and the risk for it can be minimised by reducing exposure to risk factors. Stopping tobacco use, minimising exposure to sunlight during the middle of the day, and using a broad-spectrum sunscreen can prevent lip cancers.

Summary

• Lip cancer is a type of oral cancer and is the second most common skin cancer in the head and neck
• Lip cancers commonly occur on the lower lip and predominantly affect men
• Over 90% of lip cancers are squamous cell carcinomas, with the rest being basal cell carcinomas and melanomas
• Risk factors for lip cancers include tobacco and excessive alcohol use, ultraviolet radiation, trauma, and infections like HPV and Epstein-Barr virus
• Diagnosis of lip cancer involves a good physical examination, biopsy of the lesion, and imaging studies
• Physical examination helps identify suspicious lesions such as persistent ulcers, red or white patches, thickened areas, and enlarged lymph nodes in the neck, which are indicative of the spread of cancer
• A biopsy involves removing a tissue sample from the lesion for examination under the microscope to detect cancer cells
• If lymph nodes are involved, aspiration of the contents of the node and examination will be done
• Jaw radiography, CT, MRI, and PET scans are important imaging studies performed for staging the cancer and planning treatment
• Future diagnostic tools include saliva-based liquid biopsy, AI-powered biomarker detection, and genetic testing for early and personalised diagnosis