The DNA Viruses

Herpesviridae
The viruses that belong to the Herpesviridae family are the most common
cause of viral infections of the oral cavity. All of the viruses within this
family can remain latent and subsequently reactivate to develop a
secondary infection.
•More specifically, eight serotypes are known to produce disease in
human populations.
•These include herpes simplex virus (HSV-1 and HSV-2), varicella-zoster
virus (VZV or HHV-3), cytomegalovirus (CMV or HHV-5), human herpes
viruses (HHV-6, HHV-7 or HHV-8) and Epstein-Barr virus (HHV-4).[7]
 Primary Herpetic Gingivostomatitis (PHGS)

.Primary herpetic gingivostomatitis is the primary form of

infection with herpes simplex viruses 1 and 2 (HSV-1 and HSV-2).
. Both HSV-1 and HSV-2 are double-stranded DNA viruses that
cause mucocutaneous lesions on the oral and genital
mucosa.Although HSV-2 is classically known to cause genital
infection, it may also manifest in the oral cavity.
. The most common form of transmission is contact with either
oral secretions or mucocutaneous lesions.
Viral shedding may occur despite the absence of physical lesion.
 Herpes Labialis

Herpes labialis is the secondary infection with herpes simplex

viruses, occurring in about 40% of infected individuals. It results
from the reactivation of the dormant virus in the trigeminal
ganglion, which can be precipitated by trauma, stress,
immunosuppression, and sunlight exposure.
Epidemiology of Primary Herpetic Gingivostomatitis (PHGS) and
Herpes Labialis.

The worldwide infection rates for herpes simplex viruses range

between 60 to 90%.
The incidence of herpes is slightly increased in populations with
low socioeconomic status. Infection with non-genital herpes
simplex virus, more commonly HSV-1, has decreased somewhat
since the eighties.
The infection is usually acquired in childhood by asymptomatic
shedders.
Viral shedding in oral secretions is estimated to occur in about 5
to 10% of individuals.
History and clinical findings
• Symptoms usually develop after five to ten days of incubation.
•Then oral manifestations become apparent, the classic finding
is a generalized inflammation of the gingiva and associated oral
tenderness.
•The characteristic oral lesions are small vesicles that break and
transform into shallow, painful, gray-yellow ulcers
•These lesions often involve the gingiva and buccal mucosa.
•Intact vesicles are a rare physical exam finding due to constant
intraoral friction that leads to rupture.Oral lesions often
accompany systemic symptoms, including fever, sore throat,
chills, and lymphadenopathy.
Diagnosis.
Diagnosis of primary herpetic gingivostomatitis is based on history and
physical exam findings.
• The lesions often heal spontaneously within two weeks without scarring. If the
lesions fail to resolve within ten days, an alternative diagnosis, such as erythema
multiforme or disease recurrence, should be considered.
• Recurrence in immunocompetent individuals is rare, and underlying conditions
such as acute leukemia should be investigated.Although diagnosis is usually
clinical, rises in antibody titers to HHV-1 are confirmatory.
•Additional modalities for diagnostic testing include polymerase chain reaction
(PCR) and Tzanck testing. Tzanck smears detect cytopathologic changes in
epithelial cells highly suggestive of viral infection.
A viral culture may also be used and is often considered the gold standard for
diagnosis. However, it is not routinely implemented as it causes delays.
• The diagnosis of herpes labialis is also based on clinical findings. The anatomical
location of herpes labialis allows for clinical distinction from recurrent aphthous
ulcers.
•However, if the diagnosis is questionable, an additional diagnostic evaluation can
be performed, including histologic examination, viral culture, polymerase chain
reaction, direct immunofluorescence, and in-situ hybridization.
TREATMENT

•Primary herpetic gingivostomatitis (PHGS) self-resolves after

ten to fourteen days and treatment is directed at alleviating
symptoms.
•Patients should be recommended to bed rest, have a soft diet,
and increase fluid intake.
•Oral pain is managed with systemic or topical analgesics, and
secondary infection of the lesions can be prevented with
chlorhexidine mouthwashes.
• Immunocompromised or severely unwell patients must be
indicated systemic antivirals.
•Therapy usually consists of acyclovir 200 mg orally five times
daily for five days, initiated within 24 to 48 hours of vesicle
eruption.
•Herpes Labialis lesions often heal within two weeks without
scar formation.
• However, topical antiviral medication such as penciclovir or
acyclovir 5% cream can be indicated during the prodrome stage
to reduce the duration of clinical disease.
•In immunosuppressed populations, acyclovir is the treatment
of choice.
•Intravenous foscarnet is an alternative therapy for acyclovir-
resistant strains.
Chicken Pox and Shingles
Chickenpox is the primary infection associated with the varicella-
zoster virus (VZV or HHV-3). The condition is more often seen in
pediatric populations.Transmission of viral particles usually
occurs via respiratory droplets or contact with infected lesions.

Shingles is caused by a secondary infection with the varicella-

zoster virus. It occurs due to the reactivation of the dormant
virus at the dorsal root ganglion of the spinal nerves, which may
occur in immunosuppressed states.
Epidemiology

• Chicken Pox
The widespread vaccination for varicella has significantly
reduced the incidence of chickenpox and its associated
morbidity. In 2014, the World Health Organization estimated that
about 4.2 million cases of infection developed significant
complications, and 4,200 disease-related deaths occurred
annually.The vast majority of infections are seen in children.
• Shingles
The lifetime incidence of shingles is estimated to be about 30%
for the general population, increasing slightly in patients above
the age of 85. Important patient factors that increase the risk of
infection include patients older than 50, systemic
immunosuppression, and stress.
History and Clinical findings for Chicken pox and
Shingles

Chickenpox is the primary infection with the varicella-zoster

virus.
•The classic skin lesions are pruritic maculopapular and
vesicular eruptions with an erythematous base on the trunk that
then spread to extremities
•The cutaneous eruption is often suggested to have a "dew drop
on a rose petal" appearance.
•The cutaneous manifestations can be preceded by painless
blistering on the palate, uvula, and tonsillar pillars.
Shingles
•Early signs of shingles are pain or paresthesia affecting a specific
-dermatome due to the involvement of sensory nerves.
•This is followed by an eruption of vesicular lesions that often
ulcerate and develop overlying crusting.
•The lesions appear in a specific dermatome with unilateral and
linear distributions - characteristic of the condition. Most often,
they involve the thoracic or lumbar regions.
•Oral involvement is seen when the infection affects the
maxillary or mandibular branches of the trigeminal nerve.
• The prodrome symptom of oral pain caused by shingles
infection may be confused with odontalgia leading to incorrect
diagnosis or unwarranted medical therapy.
•Moreover, a unilateral vesicular eruption on the oral mucosa
and external ear may occur and is referred to as Ramsay Hunt
Syndrome. It may be accompanied by unilateral facial nerve
Diagnosis.

The diagnosis of Chicken Pox is usually based on a classic clinical

presentation a physical exam findings.

For Shingles, reactivated herpes zoster infections are diagnosed

based on clinical findings. The most typical clinical sign is the
unilateral distribution of the lesions along a specific dermatome.
Viral cultures, PCR, or serologic testing may allow definitive
confirmation if the diagnosis is questionable.
Treatment

• Chickenpox consists of supportive measures: over-the-

counter analgesia, increased fluid intake, and a healthy lifestyle.
Aspirin should be avoided due to the risk of Reye syndrome.The
lesions are no longer contagious five to ten days after the initial
presentation once complete crusting has occurred.
• Shingles infection is treated with supportive measures, and
ulcers are expected to heal in approximately three weeks. In
immunocompromised patients, treatment for primary
infection may require high-dose oral acyclovir.
Infectious Mononucleosis and Oral Hairy
Leukoplakia

• Infectious Mononucleosis is caused by the Epstein-Barr virus

(EBV or HHV-4). The Epstein-Barr virus is associated with
primary infections but also neoplastic processes.
• The pathogenesis of mononucleosis primarily involves the
infection of B-cells in the oropharyngeal mucosa, where the
virus may remain latent.
• The primary transmission mode is via close contact with oral
secretions due to viral shedding in saliva.
• The most common clinical manifestation of infectious
mononucleosis, also referred to as "kissing disease" or
"glandular fever," is most often seen in adolescent patients.
Oral Hairy Leukoplakia is the most common oral lesion caused
by the Epstein-Barr virus in patients with AIDS
- usually observed with CD4 counts lower than 200 to
300/mm^3.
• It usually occurs in men and may represent the first sign of HIV
infection.
• It is thought to be caused by the replication of viral particles in
the mucosal keratinocytes.
Epidemiology

•Infectious Mononucleosis; Acquisition of the Epstein-Barr virus

usually occurs early in childhood and leads to latent infection. It
is estimated that greater than 90% of the global population has
acquired EBV.
The primary infection, also known as infectious mononucleosis,
usually presents during adolescence.
About 90% of mononucleosis cases are due to EBV infection.
.
•Oral hairy leukoplakia caused by EBV is almost exclusively seen
in patients with immunocompromised states, such as those with
HIV.
History and Clinical findings

• Infectious Mononucleosis
Even though the infection is asymptomatic in most cases, some
patients may experience a triad of fever, reactive adenopathy,
and pharyngitis.
The oral lesions range from petechia and erythema to
necrotizing ulcerative gingivitis.

• Oral hairy leukoplakia is an asymptomatic, white patch with

a "hairy" appearance that cannot be scraped off. It usually
develops on the lateral borders of the tongue.
Diagnosis

•Infectious Mononucleosis
The diagnosis of infectious mononucleosis is established when
there is EBV-specific IgM in the serum; this is often performed
via a mononuclear spot test (heterophile antibody). A peripheral
blood smear may be part of ancillary testing demonstrating
abnormal lymphocytes.

•Oral Hairy Leukoplakia; Diagnosis of oral hairy leukoplakia is

often established clinically.
The histopathological evaluation of the lesion may also detect
EBV.
It may be performed with PCR, direct immunofluorescence, or
in situ hybridization techniques.
Treatment

•Infectious Mononucleosis in most cases, resolves

spontaneously; thus, treatment mainly supports patient-specific
symptoms.
It is essential to avoid oral antibiotics such as amoxicillin or
ampicillin due to the risk of developing a cutaneous eruption.

•Treatment of oral hairy leukoplakia involves using topical

agents such as 0.1% vitamin A and podophyllum.
A combination of 25% podophyllin and 5% acyclovir cream is
used without lesion recurrence.
In HIV patients, antiretroviral therapy must be initiated or
adjusted to optimize the immune status.
Cytomegalovirus and Kaposi Sarcoma

• .Cytomegalovirus is also a member of the Herpesviridae family

and is otherwise known as HHV-5.
• Viral transmission occurs through the exchange of body fluids
or infected blood products. It may cross the placental barrier
and, thus, lead to congenital disease.
• Most cases are asymptomatic, particularly in
immunocompetent hosts. However, some
immunocompromised individuals may experience chronic oral
mucosal ulcerations.

• Kaposi sarcoma is the most prevalent malignancy seen in

untreated HIV patients, and it is associated with the human
herpesvirus 8 (HHV-8). It is important to note that it is most
often observed in immunocompromised patients.
Epidemiology
Cytomegalovirus; The reported rate of seropositivity to CMV in
the United States is estimated to be 50%. A higher prevalence is
seen with increasing age, particularly in developing countries
where rates may be as high as 100%. CMV is often acquired
during childhood but may also be obtained by vertical
transmission.
Kaposi Sarcoma; Four variants of Kaposi sarcoma are recognized,
each with specific disease prevalence amongst different patient
populations.
•A classic variant is often seen in males of Mediterranean or
Eastern European descent. Patient-specific risk factors, such as
chronic steroid use and diabetes, may place them at higher risk.
•An aggressive variant, African-endemic Kaposi Sarcoma, is
most often seen in patients from sub-Saharan Africa and is a
frequent carcinoma amongst HIV-negative individuals from this
• •As its name suggests, immunosuppression-related Kaposi
Sarcoma is seen in patients with chronic immunosuppression,
particularly solid-organ transplant recipients.
• Finally, AIDS-related Kaposi Sarcoma is most often observed
in HIV-infected men. However, after the introduction of
antiretroviral therapy, the incidence of the disease has
decreased. The infection's risk increases as the
immunosuppression become more severe, often seen with lower
CD4 counts.
History and Clinical findings

Cytomegalovirus
Most cases of cytomegalovirus infection are asymptomatic,
particularly in immunocompetent hosts. However, some individuals
may develop hepatosplenomegaly, thrombocytopenia, and
jaundice.
Central nervous system (CNS) involvement has also been
described.Some patients may develop non-specific oral mucosal
ulcerations, particularly in cases of coinfection with HSV or
immunocompromised status. The ulcerations may become chronic
and involve the lips, buccal mucosa, and oropharynx.
Usually, these lesions are seen in patients with CD4 counts
<100cells/mm3.
Kaposi Sarcoma
The clinical presentation of HHV-8 is characterized by red, blue, or
Diagnosis

• Cytomegalovirus infection is usually seen in patients with

HIV/AIDS with CD4 counts of <100cells/mm3.
•Diagnosis of CMV infection is generally established with PCR
or serologic testing.
•Kaposi SarcomaKaposi sarcoma is diagnosed via biopsy, and a
PCR identifies the HHV-8.
Treatment

Cytomegalovirus
The recommended antimicrobial therapy for CMV infection is
usually intravenous ganciclovir. Foscarnet and cidofovir can also
be indicated.
Similarly to oral hairy leukoplakia, improving immune status
with antiretroviral therapy is essential.

Kaposi Sarcoma
Kaposi sarcoma lesions vary in size and location. Treatment
depends on the lesion's specific features and ranges from
excision, laser destruction, and sclerosing agents to the use of
intralesional chemotherapy and radiation.
Papillomaviridae
Human Papilloma Virus
• The human papillomavirus (HPV) is a double-stranded DNA
virus that may lead to benign, premalignant, or malignant
manifestations in the oral mucosa.
• Approximately 25 strains have been demonstrated to affect
the oral mucosa; however, most subtypes have a low risk of
oncogenesis.
• Transmission occurs primarily through oral or genital contact.
Epidemiology of Human Papilloma Virus

Verruca Vulgaris, Oral Squamous Papillomas, Condyloma

Acuminatum, and Heck's Disease

• The estimated global prevalence of HPV infection is

approximately 10%. It is considered the most common
sexually transmitted disease, and the highest infection rate
is observed in women in their twenties.
• The prevalence of the disease subsequently decreases with
age.
• The majority of HPV infections of the oral cavity lead to
benign lesions. Squamous papillomas or common warts are
most frequently observed in children. Additionally, adults
between 30 to 50 years old may also develop oral papillomas.
• Specific syndromes, such as Down syndrome and Cowden
Verruca Vulgaris and Squamous Papilloma

• Verruca vulgaris is a benign lesion also referred to as the

common wart, and it is often caused by HPV subtypes 2 and
57.
• Oral squamous papillomas are the most common growth in
the oral cavity. They are benign lesions associated with
infection with HPV subtypes 6 and 11. They are often
indistinguishable clinically from verruca vulgaris,and thus,
differentiation often relies on HPV subtyping. These lesions
may be transmitted between sites by autoinoculation
History and Clinical findings

Verruca Vulgaris
Verruca vulgaris or common warts are benign oral lesions.
They are sessile and papillomatous lesions that classically affect
the lips, palate, and gingiva.

Oral Squamous Papilloma

Papillomas are the most common growth in the oral cavity.
They are benign pedunculated, exophytic lesions with a
"cauliflower" appearance that may involve the palate,
including the uvula and lips.
• It is clinically indistinguishable from verruca vulgaris.
Diagnosis

•Oral lesions associated with HPV infection, including verruca

vulgaris, squamous papilloma, condyloma acuminatum, and
Heck's disease, usually require a biopsy to establish the
diagnosis.
•Specific HPV subtypes are identified with in situ hybridization
DNA techniques.