The incidence of the disease is higher in people from certain parts of the world including South-East Asia, South Africa and the Middle East.

The exact cause of the condition is unknown. There is most evidence to support vascular infarction and ischemic necrosis of salivary gland lobules as a mechanism for the condition. Experimentally, local anaesthetic injections and tying of the arteries is reported to trigger the development of tissue changes similar to NS in lab rats. Factors which are thought to cause this ischemia are listed below, however sometimes there is no evident predisposing factor or initiating event.

- Trauma e.g. during intubation, or surgical procedures

- Local anesthetic injection

- Smoking

- Alcohol

- Diabetes mellitus

- Vascular disease, (e.g. arteriosclerosis)

- Pressure from a dental prosthesis

- Allergy

- Bulimia

- Infection

- Ionizing radiation

This type of gingival enlargement is sometimes termed "drug induced gingival enlargement" or "drug influenced gingival enlargement", abbreviated to "DIGO". Gingival enlargement may also be associated with the administration of three different classes of drugs, all producing a similar response: Gingival overgrowth is a common side effect of phenytoin, termed "Phenytoin-induced gingival overgrowth" (PIGO).

- anticonvulsants (such as phenytoin, phenobarbital, lamotrigine, vigabatrin, ethosuximide, topiramate and primidone NOT common for valproate)

- calcium channel blockers (antihypertensives such as nifedipine, amlodipine, and verapamil). The dihydropyridine derivative isradipidine can replace nifedipine and does not induce gingival overgrowth.

- cyclosporine, an immunosuppresant.

Of all cases of DIGO, about 50% are attributed to phenytoin, 30% to cyclosporins and the remaining 10-20% to calcium channel blockers.

Drug-induced enlargement has been associated with a patient's genetic predisposition, and its association with inflammation is debated. Some investigators assert that underlying inflammation is necessary for the development of drug-induced enlargement, while others purport that the existing enlargement induced by the drug effect compounds plaque retention, thus furthering the tissue response. Careful attention to oral hygiene may reduce the severity of gingival hyperplasia. In most cases, discontinuing the culprit drug resolves the hyperplasia.

Dried products such as paan masala and gutkha have higher concentrations of areca nut and appear to cause the disease. Other causes include:

- Immunological diseases

- Extreme climatic conditions

- Prolonged deficiency to iron and vitamins in the diet

Many systemic diseases can develop oral manifestations that may include gingival enlargement, some that are related to conditions and others that are related to disease:

- Conditioned enlargement

- pregnancy

- puberty

- vitamin C deficiency

- nonspecific, such as a pyogenic granuloma

- Systemic disease causing enlargement

- leukemia

- granulolomatous diseases, such as granulomatosis with polyangiitis, sarcoidosis, or orofacial granulomatosis.

- neoplasm

- benign neoplasms, such as fibromas, papillomas and giant cell granulomas

- malignant neoplasms, such as a carcinoma or malignant melanoma

- false gingival enlargements, such as when there is an underlying bony or dental tissue lesion

Tobacco smoking or chewing is the most common causative factor, with more than 80% of persons with leukoplakia having a positive smoking history. Smokers are much more likely to suffer from leukoplakia than non-smokers. The size and number of leukoplakia lesions in an individual is also correlated with the level of smoking and how long the habit has lasted for. Other sources argue that there is no evidence for a direct causative link between smoking and oral leukoplakia. Cigarette smoking may produce a diffuse leukoplakia of the buccal mucosa, lips, tongue and rarely the floor of mouth. Reverse smoking, where the lit end of the cigarette is held in the mouth is also associated with mucosal changes. Tobacco chewing, e.g. betel leaf and areca nut, called paan, tends to produce a distinctive white patch in a buccal sulcus termed "tobacco pouch keratosis". In the majority of persons, cessation triggers shrinkage or disappearance of the lesion, usually within the first year after stopping.

Although the synergistic effect of alcohol with smoking in the development of oral cancer is beyond doubt, there is no clear evidence that alcohol is involved in the development of leukoplakia, but it does appear to have some influence. Excessive use of a high alcohol containing mouth wash (> 25%) may cause a grey plaque to form on the buccal mucosa, but these lesions are not considered true leukoplakia.

This condition occurs in association with denture wearing, and so those affected tend to be middle aged or older adults. 66-75% are estimated to occur in women. Epulis fissuratum is the third most common reactive lesion that occurs in the mouth, after peripheral giant cell granuloma and pyogenic granuloma.

Erythroplakia has an unknown cause but researchers presume it to be similar to the causes of squamous cell carcinoma. Carcinoma is found in almost 40% of erythroplakia. It is mostly found in elderly men around the ages of 65 - 74. It is commonly associated with smoking.

Alcohol and tobacco use have been described as risk factors.

The condition is rare.

The typical age range of those affected by the condition is about 23–66 years of age. It usually occurs in smokers. The male to female ratio has been reported as 1.95:1, and 2.31:1.

This variation of normal anatomy is seen in the majority of adults. It is estimated about 80% of people have oral Fordyce spots, but seldom are granules found in large numbers. They are not usually visible in children, and tend to appear at about age 3, then increasing during puberty and become more obvious in later adulthood. They are more prominent in males.

Verruciform xanthoma is uncommon, with a female:male ratio of 1:1.1

If the causative factor persists, tissue will become more fibrous over time.

The exact cause of VIN is unknown. Studies are being done to determine the cause of VIN. The following factors have been associated with VIN:

- HPV (Human Papilloma Virus)

- HSV-2 (Herpes simplex Virus - Type 2)

- Smoking

- Immunosuppression

- Chronic vulvar irritation

- Conditions such as Lichen Sclerosus

There is no treatment, but because this is a benign condition with no serious clinical complications, prognosis is excellent.

A study in Sweden showed that 21.5% of smokers and 3% of nonsmokers (genetic pigmentation or unknown cause) had lesions that could be classified as an oral melanin pigmentation. A gingival melanin index in 4 degrees was established. Already with a consumption of 1-3 cigarettes a day 9.3% of all 20.333 examined showed a smoker's melanosis. Pipe smokers had smoker's melanosis in 16.8%. One year after the start of cigarette smoking a clinically visible smoker's melanosis could be seen in 12.3% of women, and 17% among men.

In cigarette smokers who quit smoking, the number of individuals with smoker's melanosis becomes slowly less frequent after 2–3 months, but can still be seen in a few former smokers three years after smoking stop.

Although clinically visible genetic melanin pigmentations in the mouth are present in several ethnic groups all over the world, more mucosal areas will be melanin-pigmentet if tobacco products are used. Smoker's melanosis is found in India, Italy, Japan, Nigeria, Sweden, Turkey, USA, and several other countries.

Smoker's melanosis is expected to be found also in other tissue surfaces exposed to tobacco and tobacco smoke, for instance lips and in skin of the fingers holding the cigarette. Future studies will also show if the use of tobacco exaggerates the pigmentation of skin.

Fordyce spots (also termed Fordyce granules are visible sebaceous glands that are present in most individuals. They appear on the genitals and/or on the face and in the mouth. They appear as small, painless, raised, pale, red or white spots or bumps 1 to 3 mm in diameter that may appear on the scrotum, shaft of the penis or on the labia, as well as the inner surface (retromolar mucosa) and vermilion border of the lips of the face. They are not associated with any disease or illness, nor are they infectious but rather they represent a natural occurrence on the body. No treatment is therefore required, unless the individual has cosmetic concerns. Persons with this condition sometimes consult a dermatologist because they are worried they may have a sexually transmitted disease (especially genital warts) or some form of cancer.

The cause is unknown, but it is thought to be caused by intracellular edema of the superficial epithelial cells coupled with retention of superficial parakeratin. Although leukoedema is thought to be a developmental condition, it may be more common and more pronounced in smokers, and becomes less noticeable when smoking is stopped. Smoking cannabis is known to be linked to this condition. It may also develop in areas subjecte to repeat subclinical irritation, caused by low grade irritants such as spices, oral debris or tobacco.

Leukoedema is common. It occurs in about 70-90% of black skinned adults and about 50% of black skinned children. The prevalence in white skinned people is considerably less, but reports range from less than 10% to more than 90%, probably varying depending upon the population studied, and the methods used in the study, e.g. examination conditions and the diagnostic criteria. The ethnic variation may be explained by genetic factors or simply because black skinned people have greater amount of melanin in the mucosa, making it appear darker (termed racial or physiologic pigmentation). This darker mucosa may make the edematous changes more noticeable, whereas in the mucosa of people with lighter skin types leukoedema gives a milder presentation.

The ICD-10 lists WSN under "other congenital malformations of mouth". It could be classified as a skin condition, or more precisely as a genodermatosis (a genetically determined skin disorder).

Vaccinating girls with HPV vaccine before their initial sexual contact has been claimed to reduce incidence of VIN.

Heck's disease (also known as focal or multifocal epithelial hyperplasia) is an asymptomatic, benign neoplastic condition characterized by multiple white to pinkish papules that occur diffusely in the oral cavity. Can present with slightly pale, smooth or roughened surface morphology. It is caused by the human papilloma virus types 13 and 32. It exhibits surface cells with vacuolated cytoplasm around irregular, pyknotic nuclei and occasional cells with mitosis-like changes within otherwise mature and well-differentiated epithelium. A distinguishing histologic feature is elongated rete ridges resembling Bronze Age axe with mitosoid bodies present. It was first identified in the Aboriginal population.

Over time, they will spontaneously regress without treatment. Possible treatment may be excisional biopsy for lesions of functional or aesthetic concern.

Epulis (; plural "epulides") is any tumor like enlargement (i.e. lump) situated on the gingival or alveolar mucosa. The word literally means "(growth) on the gingiva", and describes only the location of the mass and has no further implications on the nature of the lesion. There are three types: fibromatous, ossifying and acanthomatous. The related term parulis (commonly called a gumboil) refers to a mass of inflamed granulation tissue at the opening of a draining sinus on the alveolus over (or near to) the root of an infected tooth. Another closely related term is gingival enlargement, which tends to be used where the enlargement is more generalized over the whole gingiva rather than a localized mass.

Smoking or the use of nicotine-containing drugs is the cause to Smoker's melanosis. Also tar-components (benzopyrenes) are known to stimulate melanocytes to melanin production, and other unknown toxic agents in tobacco may also be the cause. These chemical agents have a polycyclic, chain-like structure. Environmental tobacco smoke from parents is causing smoker's melanosis in their children Swedish snuff causes a small elevation of oral melanin pigmented individuals from 3.0% to 4.7%. Nicotine tablets have shown to stimulate to melanin pigmentation of the oral mucosa.

STK is extremely common among smokeless tobacco users. Given the association with smokeless tobacco use, this condition tends to occur in adults. A national USA survey estimated an overall prevalence of 1.5% of all types of smokeless tobacco lesions, with males affected more commonly than females.