J Oral Pathol Med (2013) 42: 435–442
doi: 10.1111/jop.12009
REVIEW ARTICLE
Focal epithelial hyperplasia – an update
Ahmed K. Said1, Jair C. Leao1,2, Stefano Fedele1, Stephen R. Porter1
1
Oral Medicine Unit, UCL Eastman Dental Institute London, UK; 2Departamento de Clinica e Odontologia Preventiva, Universidade
Federal de Pernambuco Recife, Brazil
Focal epithelial hyperplasia (FEH) is an asymptomatic
benign mucosal disease, which is mostly observed in
specific groups in certain geographical regions. FEH is
usually a disease of childhood and adolescence and is
generally associated with people who live in poverty and
of low socioeconomic status. Clinically, FEH is typically
characterized by multiple, painless, soft, sessile papules,
plaques or nodules, which may coalesce to give rise to
larger lesions. Human papillomavirus (HPV), especially
genotypes 13 and 32, have been associated and detected
in the majority of FEH lesions. The clinical examination
and social history often allow diagnosis, but histopatho-
logical examination of lesional tissue is usually required to
confirm the exact diagnosis. FEH sometimes resolves
spontaneously however, treatment is often indicated as a
consequence of aesthetic effects or any interference with
occlusion. There remains no specific therapy for FEH,
although surgical removal, laser excision or possibly
topical antiviral agents may be of benefit. There remains
no evidence that FEH is potentially malignant.
J Oral Pathol Med (2013) 42: 435--442
Keywords: focal; HPV; hyperplasia; mucosa; oral
Introduction
Focal epithelial hyperplasia (FEH) is a rare benign painless
mucosal proliferation that is considered common in some
ethnic groups such as Eskimos and Indians resident in
North, South or Central America (1, 2). In these popula-
tions, up to 40% of the children can be affected by FEH (3).
FEH is clinically characterized by distinct multiple or single
mucosal papules, with a colour ranging from pink to that
of the normal adjacent mucosa, and usually measuring
1–10 mm in diameter (4–7).
Focal epithelial hyperplasia is strongly associated with
human papilloma virus (HPV) infection, the DNA of HPV
being detected in up to 80.3% of FEH lesions (8). Although
Correspondence: Stephen Porter, Director’s Office, UCL Eastman Dental
Institute, 256 Gray’s Inn Road, London WC1X 8LD, UK. Tel: +44 (0)20
3456 1038, Fax: +44 (0)20 3456 1039, E-mail: s.porter@ucl.ac.uk
Accepted for publication August 28, 2012
© 2012 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
wileyonlinelibrary.com/journal/jop
the diagnosis of FEH can sometimes be made by clinical
examination, ethnic origin and social history determination,
biopsy is still the gold standard for definitive diagnosis. FEH
has a benign nature; therefore, treatment may not be required
(5, 8, 9). However, the exophytic lesions may be removed
because of interference in occlusion or aesthetic consider-
ations (10). Surgical or laser excision, cryotherapy, topical
agents such as interferons and vitamins have been attempted
with variable short- and long-term benefits (11–15). Differ-
entiation of FEH from other HPV related conditions is
important, especially condyloma acuminatum (CA) or
venereal warts, which are often acquired sexually and
associated with sexual abuse if in children (8, 11).
Epidemiology
Worldwide FEH is rare; however, it is frequently observed
among specific ethnic and racial groups. FEH is found in a
high frequency among Inuits and Indians resident in North,
Central and South America, Eskimos from Greenland and
North Canada, and descendants of Khoi-San in South Africa
(2, 16). As the disorder is rare in other communities, there
are few population studies, most of which being of
geographical regions and/or ethnic groups in which FEH
is common. The prevalence of FEH in the Eskimo
population varies from 7 to 36% (17). In South Africa, a
3-year longitudinal study of the prevalence and the
incidence rates of FEH between two well-defined commu-
nities (Garies and Kamieskroon), both descended from the
Khoi-San indigenous population and of similar ethnicity,
socioeconomic status and geographical location, found no
significant differences in the prevalence and the incidence
rates between the two communities, with prevalence rates
ranging from 7 to 13%, and incidence rates ranging from 38
to 68 per 1000, but there were variations in size, number and
duration of the lesions along the whole study period, which
suggests that FEH tends to affect specific ethnic and age
groups; however, the long-term behaviour of the lesions is
unpredictable (18).
The prevalence of FEH among the children of the Embera-
Chami community in Colombia has been reported to be 13%
(10). A cross-sectional study of 587 Waimiri-Atroari Indians
from Central Amazonia in Brazil found FEH to be the second
most common oral mucosal disorder, with a prevalence rate
 Focal epithelial hyperplasia
Said et al.
436
up to 21%, and the only oral mucosal disease of 13.3% of the
children and 8.6% of the adults. In this community, no
common habit with respect to beverages consumption, quid
chewing, tobacco smoking or alcohol drinking usage could
be identified that might be related to FEH development (19).
In contrast, a retrospective study in Mexico found only nine
of 1000 patients attending a dermatology unit to have FEH
(20). In another study in Mexico, the prevalence of FEH has
been reported to be only 0.026% (72).
Focal epithelial hyperplasia is more common in females
than males, the ratio found being as high as 5:1 (2, 10, 12,
20, 21). The exact cause of the higher incidence in females
is not known. Some authors have proposed that this might
be related to the living conditions associated with women in
some ethnic groups (22), however, there is no consistent
evidence to support this.
Clinical features
The individual lesions are discrete and range in size from 1
to 10 mm in diameter. Lesions can change in size over
months to years (4,7,18), sometimes coalescing to form
larger lesions. A cobblestoned or fissured pattern may arise
if there is coalescence of large numbers of individual lesions
(8). Ulceration, erosion and malignant transformation are
not features of FEH (23).
Focal epithelial hyperplasia is considered to have two
distinct clinical forms: papulonodular and papillomatous
(21). The papulonodular variant is more common, lesions
tend to be pink and smooth surfaced. This variant usually
occurs on the buccal and/or labial mucosa, and the
commissures of the mouth (21). The papillomatous variant
of FEH is less common and usually arises on the
masticatory mucosa such as the tongue and attached
gingiva. Lesions of this type are white in colour and have
a rough pebblish surface (21). The tendency of these clinical
types to affect different oral mucosal surfaces is probably a
reflection of the affected epithelium. The loose underlying
dermis of the labial and buccal mucosa will favour
endophytic growth, while the dense dermal connective
tissue of the attached gingiva and tongue will favour an
exophytic growth (21). The clinical presentation may also
be influenced by patient age. FEH lesions affecting younger
patients tend to be multiple, exophytic and nodular, while
few or single flat and papular lesions more commonly affect
older patients (19, 24). Of course, the association between
the number of the lesions and the age of the patients may
reflect the behaviour of FEH lesions, which tend to regress
spontaneously with time (25).
Focal epithelial hyperplasia rarely affects the gingiva or
the hard palate (7,18,20,21) and seems to be particularly
uncommon on the floor of mouth, soft palate and oropharynx
(2, 26). The lesions of FEH almost always arise on multiple
sites in each individual. Single-site involvement by multiple
lesions is very uncommon (26). The differential diagnosis of
FEH includes a wide range of disorders (Table 1).
In children, it is very important to differentiate FEH from
the sexually acquired CA or venereal warts, which may
indicate sexual abuse of them (8, 11). CA is associated with
HPV 6 and 11 (27), and mostly affect the anogenital skin
and mucosa (28).
J Oral Pathol Med
Aetiology
Viral factors
A viral basis for FEH is supported by several observations.
HPV DNA has been found in the majority of examined FEH
lesions (2, 10, 11, 15, 29–32); an infectious nature of FEH is
supported by the increased frequency of lesions among
individuals from the same family, and in patients living in
poverty with limited or no access to medical care services
(20). The strong tendency for lesions to affect the buccal and
labial mucosa may be considered as a proof of transmission
of HPV infection by direct oral contact (18). The viral basis
may be also supported by a tissue-site specificity, which has
been suggested by some investigators who observed that
HPV 13 was more commonly found on keratinized
epithelium, whereas HPV 32 is more commonly detected
on non-keratinized surfaces. Although this site specificity
has not been proven statistically, it may indicate the role of
anatomical sites in determining susceptibility to infection
(33). The wide variation in size, number and healing time
resembles the behaviour of other HPV-related lesions (18).
Depending upon the methods of detection, HPV DNA has
been found in 50–100% of examined FEH lesions (34–37).
Many HPV genotypes have been detected in examined FEH
lesions. Human papillomavirus genotypes 1, 6, 11, 16, 18
and 55 have been detected in FEH lesions (33, 37–41).
Indeed, it is possible to detect more than one HPV genotype
in the same patient (e.g. HPV 11 + 13) (37), and rarely is no
HPV DNA found (41). One patient was diagnosed to have
FEH containing HPV 24 (a type usually associated with
epidermodysplasia verruciformis and also detected in dys-
plastic PUVA keratosis, but not demonstrated in malignant
changes) (42, 43). This patient eventually developed malig-
nant changes (44) but there was some doubt about the
reliability of the diagnosis of FEH (23). Although it has been
suggested that HPV 13 and 32 are unique to the oral mucosa
(26, 45), HPV 13 (and other HPV type) may cause (or been
associated with) perianal bowenoid papulosis in individuals
with HIV disease (46). A case of a 7-year-old native South
American girl with HPV 13-associated conjunctival papil-
loma and a history of oral FEH that regressed spontaneously
has been reported (47).
Human papillomavirus 13 and 32 are also detected in
condylomata acuminatum (CA) and oral squamous cell
papilloma (OSCP) (33, 34, 45, 48, 49). As the histopatho-
logical features of CA and OSCP are similar to that of FEH,
it may be that several HPV types give rise to similar local
tissue changes that manifest in clinically different ways (26).
Risk factors
The epidemiological factors that may be related to FEH (e.g.
poverty, dietary insufficiency and close living conditions)
favour the notion that FEH has an infectious cause (4, 18, 26,
50). FEH has been observed in patients with HIV disease (51).
Although HIV infection is certainly not the main cause of
FEH development, HIV-infected patients are more likely to
develop oral HPV infection, and HPV was detected in 25.3%
among HIV-positive patients, whereas it was detected only in
7.6% among healthy individuals (52). HIV-positive patients
are more likely to be infected by more than one HPV type, and
also to be infected with a high-risk genotype such as HPV 16
(52). However, the exact role of HIV-positive infection in the

Table 1 Differential diagnosis of FEH
Disorders
Condyloma acuminatum (Venereal warts)
Verruca vulgaris (Common warts)
Squamous cell papilloma
Multiple endocrine neoplasia syndrome type II b
White sponge naevus
Verruciform xanthoma
Verrucous carcinoma
Cowden’s syndrome
Crohn’s disease
Sialadenoma papilliferum
Focal dermal hypoplasia (Goltz–Gorlin syndrome)
Neurofibromatosis
Tuberous sclerosis
Epidermal naevus syndrome
Amyloidosis
Darier’s disease
Mucosal neuroma
Fibromas
development of HPV infection in the mouth remains unclear
(53). Only 2% of the oral lesions of a group of patients with
HIV disease in Venezuela had FEH (54), other instances of
FEH in HIV disease have always been in individuals residents
in countries where FEH has been reported (1, 14, 30, 55). FEH
of HIV disease is more likely to be associated with HPV 32
than HPV 13 in the most of these cases (30, 55). However, a
few samples have been reported with detection of HPV 13
(14). The level of immunodeficiency (as detected by the
CD4+ T-cell count) does not seem to affect the development
of FEH (55), and FEH does not seem to be a feature of immune
reconstitution syndrome unlike some other HPV-associated
diseases (e.g. oral warts) (73). FEH has been observed in an
individual who had been iatrogenically immunosuppressed
(56) and was persistent in two siblings with leucocyte
adhesion deficiency (57). In addition, a 12-year-old girl with
the late onset adenosine deaminase (ADA) deficiency
presenting with Heck’s disease has been reported (58).
Genetic predisposing factors
The clustering of FEH in certain geographical regions,
together with the interfamilial occurrence, suggests that
Focal epithelial hyperplasia
Said et al.
437
Differentiation features
Usually small proliferation of wart-like masses
Usually small proliferation of wart-like masses
Usually small proliferation of wart-like masses
Autosomal dominant characterized by sessile
lesions typically on the tongue (neurofibromas),
patient may have a marfanoid facial appearance,
may have high risk of thyroid medullary carcinoma
and pheochromocytoma
Autosomal dominant, characterized by thickened
white spongy oral mucosa, may affect vaginal or
anal mucosa
Single lesion, usually pink in colour, seems to occur
in areas exposed to irritation or trauma
Slowly growing wart-like masses, which are considered
a variant of squamous cell carcinoma
Autosomal dominant condition, typically associated with
multiple hamartomas, patients have an increasing risk
of developing cancers (especially of thyroid and breast)
Associated with lip swelling, mucosal tags, lower abdominal
pain, abnormal bowel habits
Papilloma like lesions, more common among adult
males, typically found on the palate
Autosomal dominant characterized by multiple nevoid
basal cell carcinoma, skeletal abnormalities and
keratocyst formation
Autosomal dominant may be associated with cutaneous pigmentation,
epilepsy, other neurological features
Autosomal dominant may be associated with subungual fibroma, cutaneous
hypopigmentation, enamel defects, epilepsy or
mental impairment
Congenital hamartomas characterized by epidermal nevi
and multiple organ abnormalities
Widespread lesions may be associated with bleeding
tendencies and various organ failures
Autosomal dominant, usually wart-like papules or plaques
Characterized by circumscribed lesions, elastic and
hard to palpation
Submucosal proliferation, slow growing lesions of variable size
FEH may have a genetic component to its aetiology (26,
59). In a study of 22 Mexican individuals, FEH has been
found to be increased in the presence of HLA-DRB1*0404
(60). This HLA-DR allele is commonly present in some
ethnic groups of indigenous Americans descent, such as
the Mazatecans, Nahuas and Mexican mestizo populations
(61), and thus raises the notion that there is a genetic
component to FEH. A genetic basis to FEH has been
suggested in view of FEH being observed in a caucasian
girl with a Brazilian Xavante Indian descent (via her
paternal grandfather) (62), but there is still the possibility
of the infection having simply been acquired from the
grandfathers.
Focal epithelial hyperplasia has been reported to be
associated with other viral infections at the same time in
33% and 41% of the patients in some studies (48, 60);
among these viral infections, the common wart was the most
common condition to be seen (60). Although the relation
between FEH and other HPV infections has not been
investigated by workers previously but it does support the
notion that a genetic factor in affected persons increases the
susceptibility to different HPV infections (60).
J Oral Pathol Med
 Focal epithelial hyperplasia
Said et al.
438
Diagnosis
The diagnosis of FEH can often be made by clinical
examination and review of the patient’s social history (e.g.
to identify the racial background, socio-economic status,
living conditions and any family history of similar lesions
affecting close or first-degree relatives living in the same
household). Definitive diagnosis, however, always warrants
histopathological examination and detection of HPV within
the lesional tissue. Local application of 3% acetic acid
solution has been used in some studies to aid localization of
a biopsy site when the lesions were not easily detected (but
suspected) clinically (10, 29).
Serial sectioning of paraffin-embedded biopsy material
may be necessary to detect the characteristic nuclear
abnormalities, which may not be observed in a single
sectioning procedure (26, 29, 63).
Focal epithelial hyperplasia lesions have distinct histo-
pathological features. These include epithelial hyperplasia
with acanthosis and parakeratosis. Thickening and focal
elevations of the epithelium may extend in an upward
direction without involvement of the underlying dermis. The
rete ridges are widened, elongated, thickened and fused to
form horizontal anastomosing and clubbing called ‘bronze
age battle-axe’ or ‘clubs’. The individual cells have
cytopathological changes comprise ballooning degenera-
tion, nuclear fragmentation and cytoplasmic enlargement.
The nucleus shape is similar to that of mitosis termed
‘mitosoid figures’. Additionally, koilocytes characterized by
a clear cytoplasm and absent nucleus are common, these
predominantly occurring in the superficial cell layers and
sometimes the spinous, but not the basal layers. There is
little inflammatory infiltrate, although dilated capillaries are
occasionally present (1, 2, 6, 10, 20, 25, 29, 62–64).
Dyskeratosis, binucleation, exocytosis and basal vacuola-
tion have been occasionally observed (10).
The routine detection of HPV in FEH lesions remains
difficult. The detection of HPV in FEH lesions by the
different available detection methods is not always 100%
positive, and each method has its own advantages and
disadvantages. Serum immunological markers are used for
the detection of HPV antibodies by ELISA, but the presence
of serum HPV antibodies is not considered an indication for
the presence of active infection (74). In situ hybridization
(ISH) has the disadvantages of being time-consuming and
has a low sensitivity (7, 20–49) (75). Southern blot (SB) has
been one of the gold standard methods used for the
detection of HPV and has the advantage of differentiation
between episomal DNA (which is extra chromosomal and
autonomously replication) and DNA that is integrated
within host chromosome (76). It has a high sensitivity and
can detect about 0.1 copy of HPV DNA per cell (75);
however, it requires to isolate and purify the cellular DNA
and digesting it into fragment (77). Although polymerase
chain reaction (PCR) is one of the most specific and
sensitive methods that has been used for the detection of
HPV DNA (77), there is still a possibility of false negative
results due to primer selection, and there is a probability of
sample contamination; furthermore, the presence of HPV
DNA may not always indicate the presence of active viral
production (74). In general, many causes have been related
J Oral Pathol Med
to failure in HPV detection such as failure to carry out the
serial sections procedure during tissue specimen processing
due to lack of the study material, for example, may lead to
missing of positive cells (64). DNA degeneration may also
reduce detection rate of HPV (65). During fixation in
formalin, DNA of paraffin-embedded specimen may have
less accessibility for the viral probes due to the effect of
formalin (66). The detection technique may miss the low
amount of HPV DNA in some examined FEH lesions (64).
Contamination is also possible by gloves, instruments or
aerosolization (74). In some studies, loss of HPV detection
in FEH lesions may be due to the presence of an HPV
genotype, which was unknown at the time of the study and
thus appropriate probes were not used (64).
Treatment
Treatment of FEH is not always indicated as the lesions are
asymptomatic, often regress spontaneously (within months to
years) and have no malignant transformation. Nevertheless,
the lesions can be unsightly (e.g. if they are on the anterior
gingiva or lips) and can be physically irritating the patients
(4, 9, 20, 22, 62, 67). In one study from Guatemala, about
49% of 110 patients complained that the lesions interfered
with occlusion and mastication and sometimes caused
accidental biting of the lesions; however, most treatment
was provided for aesthetic reasons (26). There remain no
randomized controlled trials of the treatment of FEH.
A variety of treatment modalities have been utilized with
different results and recurrences rates (Table 2).
Suggested first line treatments of FEH are removal of the
lesions by surgical excision (scalpel surgery), cryotherapy,
CO2 laser (in continuous mode or in time-repeated modes),
electrocoagulation or electrodessication. However, these
procedures are invasive and some are expensive (2, 20, 68).
Surgical excision (i.e. scalpel excision) is likely to be the
most commonly employed method of treating FEH. How-
ever, this can give rise to post-surgical bleeding, pain and
later scarring. CO2 laser excision may be less likely to cause
bleeding, pain or scarring (68) and has been suggested by
some authors to be the more effective mean of managing
FEH lesions (78). Diode Laser therapy has also been used in
a patient with FEH associated with HPV13 infection (69).
However, such techniques are not available in all units. In
addition, there remains no study that demonstrates that laser
excision/ablation is more effective than surgical removal.
Topical or systemic interferon (by virtue of its antiviral
action) has been reported to be of potential benefit in the
treatment of FEH especially in instances of diffuse
involvement (13, 15). Interferon alpha may be more
effective than interferon beta (13). Intramuscular interferon
alpha-2a (4.5 million IU, three times per week for
14 weeks) caused a partial regression and disappearance
of FEH lesions within 8 weeks following cessation of
treatment (13). Intralesional interferon alpha also has been
reported to be used with partial regression of the lesions
(44). Although originally licensed for CA, topical interferon
beta has been suggested to be an effective, non-invasive,
simple, non-expensive treatment of FEH (15). One patient
given interferon beta (fiblaferon gel®) topically five times
per day for 12 weeks developed complete remission of the

Table 2 Reported therapies of focal epithelial hyperplasia
Treatment
No treatment (two patients).
Topical interferon b
Interferon a-2a
No treatment
No treatment (six patients)
25% podophyllin and
cryotherapy/with no response
CO2 laser
No treatment
Only largest portion removed
surgically for biopsy
CO2 laser
Electrodessication of largest lesion
3 episodes of CO2 laser in one patient.
No treatment
Electrocoagulation and acitretin 25 mg/day
CO2 laser and interferon a-2b
No treatment
Imiquimod
a
Leucocyte adhesion deficiency.
b
HIV disease.
lesion with no recurrence for 7 months after the end of this
treatment (15).
Imiquimod (5% cream) applied three times per week
caused complete resolution of FEH lesions after 3 months
and no recurrence in a 5 month follow-up period (79). More
recently, Imiquimod has also been used to successfully treat
two siblings diagnosed with FEH (70). Imiquimod is a topical
immune response modifier used originally for anogenital
warts, later being employed successfully for many other
conditions such as genital herpes, actinic keratoses, superfi-
cial basal cell carcinoma, vulvar intra-epithelial neoplasia,
metastatic melanoma and Bowen’s disease (80, 81). Imiqui-
mod enhances the immune system by inducing innate and
acquired responses (82). Imiquimod activates the innate
immune system by binding to cell surface receptors resulting
in the production of cytokines such as interferon-a (IFN-a),
tumour necrosis factor-a (TNF-a) and interleukins from
monocytes, macrophages and dendritic cells (83). Imiquimod
also activates the acquired immune system (mainly the
cellular immune response) by the stimulation of natural killer
cells, macrophage, proliferation and differentiation of
B-lymphocytes to produce immunoglobulins and activate
function of cytotoxic T-lymphocytes that act against virally
infected or tumour cells (81). Local skin irritation, erythema,
erosion, flaking, oedema and excoriation have been reported
to be the likely side effect of Imiquimod (82). Imiquimod
should be avoided immediately following surgical proce-
dures or where there is an infection, and as it induces
photosensitivity, imiquimod cannot be applied to sun-
Focal epithelial hyperplasia
Said et al.
439
Outcome Authors
1-Complete resolution in sometime Mealey et al. (57) (case 1)a
within 3-year period
2-Complete resolution after 26 months
Complete resolution after 12 weeks/no Steinhoff et al. (15)
recurrence after 7 months
Partial resolution after 2 months Kose et al. (13)
Unchanged after 2 years Morrow et al. (9)
4/6 complete resolution within 18 months Nartey et al. (21)
2/6 persist over 3 years
Complete resolution within about Cohen et al. (11)
9 months/no recurrence after 6 months
Resolution/no recurrence after 18 months Luomanen (78)
Unchanged after 1 year Durso et al. (24)
No recurrence at site of surgery and no Martins et al. (62)
change in remaining lesions after 24 months
Resolution after 2 weeks/no recurrence Bassioukas et al. (68)
after 20 months
Good healing at operation site/patient lost Michael et al. (2)
to follow up
Recurrence after 8 months Moerman et al. (14)b
Resolution after 2 weeks/recurrence
after 3 months
Resolution
Spontaneously resolved and recurred Viraben et al. (55)b
after 3 years
Recurrence after 1 month Vilmer et al. (30)b
Resolution/no recurrence after 2 years Akyol et al. (50)
Unchanged after 2 months Landells et al. (84)
Resolution after 3 months/no Maschke et al. (79)
recurrence after 5 months
exposed surfaces (80). A patient with FEH refractory to
different treatment modalities (interferon, levamisole, acitre-
tin and electrocauterization) was treated successfully with
CO2 laser combined with interferon alpha-2b (3 9 3 million
IU per week). The interferon alpha-2b treatment was
continued for 8 months following laser therapy, and no
recurrences were reported over the next 2 years (50).
Systemic retinoid (acitretin) with or without surgery or
electrocoagulation has been suggested to be a potential
therapy (30, 44). However, there are no consistent data to
suggest clinical benefit, and there is a risk of adverse effects
of the systemic retinoid (30).
Other suggested agents for treatment of FEH include
topical podophyllin resin, levamisole or vitamins (8,12), but
there are few, if any, supportive data.
Long-term behaviour
The long-term behaviour of FEH lesions is unclear, in
particular if recurrence is likely. FEH lesions may progress
and increase in size, remain unchanged and persist for several
years or may undergo spontaneous regression and resolution
within months to years (5, 8, 11, 12, 21, 24, 25, 63, 71). FEH
lesions may show a wide variation in duration. In one study,
the duration of the lesions varied from several weeks to
30 years (20). Recurrence of FEH lesions can occur despite
effective initial treatment or spontaneous healing (8, 11, 71).
Yearly examination in a 3-year longitudinal study of two
communities in South Africa of similar ethnic background,
J Oral Pathol Med
 Focal epithelial hyperplasia
Said et al.
440
socioeconomic status and geographical region demonstrated
that the lesion size, number and duration are often
unpredictable (19). Over a 3-year period, some FEH lesions
persisted; in four patients, FEH lesions were only observed
in the second year, while with two patients, the FEH lesions
were observed in the first and third years only. In addition,
recurrence may occur at the same oral mucosal sites as
previous disease (19).
Focal epithelial hyperplasia is a benign disease having no
malignant potential (4, 9, 13, 24, 62). One instance of
malignant transformation of FEH associated with HPV 24
has been reported (44), but the definitive diagnosis of this
lesion has been questioned (23).
Immunocompromised patients (e.g. those with HIV
disease) have been observed to have persistent or recurrent
FEH (14, 30, 55, 57). FEH persisted for 2–5 years in two
siblings with leucocyte adhesion deficiency (57). While this
may seem logical, there is no evidence that profound
immunodeficiency predisposes to, or influences, the clinical
course of FEH.
Conclusion
Focal epithelial hyperplasia is a painless benign mucosal
disease, which is mostly observed in specific ethnic groups
and geographical regions; however, isolated cases have been
reported worldwide. FEH is mostly a disease of childhood and
adolescence and is generally associated with people who live
in poverty or of low socioeconomic status. HPV genotypes
have been associated and detected in the majority of FEH
lesions, and HPV DNA has been found in 50–100% of FEH
lesions. FEH is a benign disease that is sometimes sponta-
neously resolved. Treatment can be required because of
aesthetic reasons, or interference with occlusion, and consists
of removal of the lesions. Recurrence of FEH lesions can
occur after spontaneous regression or following treatment
(11, 8, 71). The disease does not have a maligant potential.
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Acknowledgements
This work was undertaken at University College London/University College
London Hospital Trust who received a proportion of funding from the
Department of Health’s National Institute for Health Research Biomedical
Research Centre (BRC) funding scheme.