Chapter 13 STDs

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Sexually Transmitted Diseases
 Sexually transmitted diseases (STDs) continue to
be a major health problem worldwide
 The worldwide burden is difficult to estimate, but there
are more than 30 infectious diseases known to be
transmitted through sexual contact
 World Health Organization (WHO) reports there are
almost one million new cases each day collectively for
the 4 most prevalent reportable bacterial STDs
(chlamydia, gonorrhea, trichomoniasis, syphilis)
 The Centers for Disease Control (CDC) have reported
incidence estimates for these same 4 STDs of close to 5
million new infections per year in the U.S.

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Sexually Transmitted
Diseases (cont’d)
• STDs have important implications for the dental
team and prompt recognition, diagnosis and
management of STDs is of paramount
importance
 Oral health care providers may intercept patients who
have STDs while eliciting their history, and/or by
recognizing oral manifestations of STDs during exams
 Patients may not always divulge that they have a STD,
or they may have asymptomatic disease and be
unaware that they have an active infection
 STDs can be transmitted by contact with blood, saliva,
oral lesions, or asymptomatic viral shedding

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Diseases (cont’d)
 The dental team should assume that all patients
are potentially infectious and must adhere to
standard infection control precautions
 A single STD is accompanied by additional STDs in
about 10% of cases, and STDs increases the risk for
human immunodeficiency virus (HIV) infection
 Prevention is critical and oral health care providers can
provide patient education to minimize transmission,
particularly concerning oral contact.
 Dentists do not elicit a sexual history on patients, but
should be familiar with how to do so if the need arises

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Diseases (cont’d)
 Understanding the epidemiology,
etiopathogenesis (cause and development of
a disease or abnormal condition), clinical
course and manifestations, diagnosis and
medical management of STDs can provide a
strong basis for the identification of the oral
manifestations and the dental considerations
of patients with STDs

6
Complications
 STDs are transmitted by intimate
interpersonal contact, which can result in oral
manifestations
 Pathogens responsible for STDs can exhibit
antimicrobial resistance, thus proper
treatment is essential
 Patient interaction with dental health care
workers can be an important component of
STD control by providing opportunities for
diagnosis, education, and information
regarding access to treatment

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Gonorrhea
 Gonorrhea is an STD of worldwide distribution
caused by Neisseria gonorrhoeae
Humans are the only natural hosts for this disease
It is transmitted almost exclusively via sexual
contact, whether genital-genital, oral-genital, or
rectal-genital
Gonorrhea primarily infects the urethra, cervix, the
rectum, and oropharynx, although it can infect other
sites such as the conjunctiva

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Epidemiology
 Gonorrhea is the second most commonly
reported infectious disease and STD in the
United States, behind chlamydial infection
 There were 350,062 new cases in the U.S. reported
in the to the CDC in 2014
 This shows an increase in 10 cases per 100,000
over the last 5-year interval
 More new cases were reported in men than women,
more than 50% by in 15-24 year olds
 Non-Hispanic blacks show >10 times the rate of
whites, although that rate is decreasing

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Etiopathogenesis
 Gonorrhea is caused by N. gonorrhoeae, an
aerobic gram-negative β-proteobacteria
 N. gonorrhoeae replicates easily in warm, moist
areas and preferentially requires high humidity and
specific temperature and pH for optimum growth
(like human mucosae)
 It is a fragile bacterium readily killed by drying, but
develops resistance to antibiotics rather easily
 Many strains have become resistant to penicillin,
tetracycline, and quinolones, making it a major
global issue

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Etiopathogenesis (cont’d)
 N. gonorrhoeae displays differential
invasiveness based on the type of host
epithelium with which it interacts
 Columnar epithelium (found in the mucosal lining of
the urethra and cervix) and transitional epithelium
(found in the pharynx and rectum) are highly
susceptible to infection
 Stratified squamous epithelium (skin and mucosal
lining of the oral cavity) is generally resistant to
infection

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Clinical Presentation
 Infection in men usually begins in the anterior
urethra after sexual exposure and a 2 to 5
day incubation period
 The acute infection is symptomatic and leads to
urethritis, a purulent urethral discharge, and dysuria
 Infection may remain localized or may extend
posteriorly to involve the epididymis (which can lead
to infertility), prostate, seminal vesicles, or bladder

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Clinical Presentation (cont’d)
 Infection in the majority of women is
asymptomatic and incubation takes 5 to 10
days
 Infections lead to a cervicitis with resultant purulent
drainage and dyspareunia, and less commonly, a
urethritis
 Ascending infection may involve the endometrium,
fallopian tubes, ovaries, and pelvic peritoneum and
gonorrhea is a common cause of pelvic
inflammatory disease (PID)

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 In both genders, ano-rectal gonorrhea may
occur. Though it is commonly less intense
than genital infection, similar symptoms
(copious purulent discharge, soreness, pain)
may be noted
 Pharyngeal infection is detected in 3% to 7% of
heterosexual men, 10% to 20% of heterosexual
women, and 10% to 25% of homosexual men
 Oropharyngeal infection is typically asymptomatic or
manifests as a mild sore throat, and clinically is
associated with diffuse, nonspecific inflammation

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 In symptomatic cases, the oropharynx may
appear erythematous, with tiny pustules can
involve the palatine tonsils which become
enlarged with or without a yellowish exudate
and may be associated with cervical
lymphadenopathy
 The likelihood of transmission of pharyngeal
gonorrhea to the genitalia is less common than that
of genital–pharynx or genital-genital transmission

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Gonorrhea in the Oropharynx

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Laboratory and
Diagnostic Findings
 Gram stain demonstrating Gram-negative
diplococci within neutrophils is the best point-
of-care diagnostic for N. gonorrhoeae
infection
 In women and asymptomatic men, nucleic acid
amplification testing (NAAT) is widely available and
recommended by the CDC as a first-line diagnostic
 Culture for N. gonorrhoeae is indicated in patients
receiving a CDC-recommended antimicrobial
regimen, yet maintain a NAAT-positive result

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Medical Management
 Due to antimicrobial sensitivity, the CDC now
recommends dual therapy of ceftriaxone and
azithromycin to treat uncomplicated gonococcal
infection of the cervix, urethra, pharynx, rectum
 Alternative regimen, when ceftriaxone is unavailable,
cefixime and azithromycin
 If cephalosporin allergy, gemifloxacin and
azithromycin, or gentamicin and azithromycin
 Sexual partners should be tested, treated; treated
patients with persistent signs or symptoms should
undergo culture and antibiotic sensitivity testing

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Dental Considerations
 A patient with a known recent gonorrhea infection
that has been administered appropriate antibiotic
therapy poses little threat of disease transmission
to the dental team
 Dental care can be provided within days of
beginning antibiotic treatment
 Patients with an active pharyngitis and other oral
signs or symptoms suggestive of an active infection
should be promptly referred to a physician for further
evaluation

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Oral Manifestations
 Reports of gonorrhea involving the oral cavity
(or any sites other than the oropharynx) are
rare
 Encountering patients with a symptomatic
pharyngitis warrants referral for further
evaluation

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Syphilis
 Syphilis is an acute and chronic STD, caused
by Treponema pallidum
 There are early infectious stages (primary and
secondary syphilis), and if untreated, there is a
latent stage, followed by a non-infectious late stage
(tertiary syphilis)
 Humans are the only known natural hosts for
syphilis
 Syphilis remains an important infection in
contemporary medicine because of the morbidity it
can cause

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Epidemiology
 There were 19,999 new primary and
secondary syphilis cases reported in the U.S.
to the CDC in 2014 (6.3 cases per 100,000),
a rate that has almost doubled over 10 years
 The estimated number of new and existing infections
in 2014 was 63,450
 Over 10 men are infected for every woman, the
highest incidence in black males, and the greatest
increases in men who have sex with men
 Congenital syphilis occurs when the fetus is infected
in utero by an infected mother

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Etiopathogenesis
 The etiologic agent of syphilis is Treponema
pallidum, which is a slender, fragile anaerobic
spirochete
 It is transmitted predominantly sexually; however,
transmission also can occur through nonsexual
means, like blood borne infection or to a fetus
 Indirect transmission by fomites is possible but
uncommon
 T. pallidum is easily killed by heating, drying,
disinfecting, and using soap and water

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 Evidence suggests that T. pallidum does not
invade completely intact skin but can invade
intact mucosal epithelium and gain entry
through minute abrasions or at the hair
follicles
 A few hours after invasion, bacterial spread to the
lymphatics and the blood stream occurs, resulting in
early widespread dissemination of the disease
 The risk of transmission occurs during the primary,
secondary, and early latent stages of disease, but
not in late syphilis

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 Primary syphilis
 Secondary syphilis
 Latent syphilis
 Tertiary syphilis
 Congenital syphilis

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 Clinical manifestations of syphilis are
classically divided according to stages of the
disease
 Each stage has its own specific signs and symptoms
related to disease duration and antigen-antibody
responses
 The stages are primary, secondary, latent, tertiary,
and congenital
 Many infected persons do not develop symptoms for
years, yet remain at risk for late complications if the
infection is not treated

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 Primary syphilis
 Characterized by the chancre, a solitary, round, firm,
lesion that develops at the site of contact with the
infectious organism
 The chancre usually occurs within 2 to 3 weeks after
exposure
 The lesion begins as a small papule and enlarges to
form a surface erosion or ulceration, covered by a
yellowish hemorrhagic crust If adequate treatment is
not provided, the infection progresses to secondary
syphilis

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 The chancre usually subsides in 3 to 6 weeks
without treatment, leaving variable scarring in
the form of a healed papule
 More than 80% of chancres occur on the genitalia,
and the most common extra-genital site is the oral
cavity/oropharynx
 If adequate treatment is not provided, the infection
progresses to secondary syphilis

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 Secondary syphilis
 The manifestations of secondary syphilis appear 6 to 8
weeks after initial exposure
 Symptoms and signs of secondary syphilis develop in
80% of patients and include fever, arthralgia and
malaise, generalized lymphadenopathy, and patchy
hair loss
 Generalized eruptions of the skin and mucous
membranes also occur and include condyloma lata or
wart-like growths on the genitalia
 The papules of the rash are well demarcated and
reddish brown with a predilection for the palms and
soles; they typically are not itchy

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 Oral manifestations of secondary syphilis
include pharyngitis, papular lesions,
erythematous or grayish-white erosions
(mucous patches), irregular linear erosions,
and, rarely, parotid gland enlargement
 The lesions of skin and mucous membranes are
highly infectious
 Without treatment, secondary syphilis ultimately
resolves; however, infection progresses to latent or
late stages

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Mucous Patch Associated with
Secondary Syphilis

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 Latent syphilis
 Defined as the third stage of the untreated infection
in which the patient displays seroreactivity but no
clinical evidence of disease
 This state of infection is divided into early latent
syphilis (disease acquired within the preceding year)
and late latent syphilis (disease present for longer
than 1 year)

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 During the first 4 years of latent syphilis,
patients may exhibit mucocutaneous relapses
and are considered infections
After 4 years, relapses typically do not occur, and
patients are considered non-infectious
The latent stage may last for many years or, in fact,
for the remainder of the person’s life
In some untreated patients, however, progression
to tertiary syphilis occurs

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 Tertiary syphilis
 This late stage of the disease occurs in 10%-40% of
untreated persons, generally several years after
disease onset
 It is the destructive stage of the disease although
patients are considered non-infectious
 Some have classified tertiary disease into three
subtypes: neurosyphilis, cardiovascular, and
gummatous disease

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 Neurosyphilis can result in a meningitis-like
syndrome, Argyll Robertson pupils, altered
tendon reflexes, general paresis, tabes dorsalis
difficulty in coordinating muscle movements, or
insanity
 Cardiovascular syphilis is essentially vascular in
nature and the end product of an obliterative
endarteritis
 The gumma, which is the classic localized lesion
of tertiary syphilis, may involve the skin, mucous
membranes (including the oral cavity), bone, or
within any organ

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 Congenital syphilis
 Syphilis or its sequelae occur in the newborn if the
mother is infected while carrying the child
 The disease is transmitted to the fetus in utero, as early
as 9-10 weeks
 The sequelae of early infection include osteochondritis,
periostitis, rhinitis, rash, and ectodermal changes
 Syphilis contracted during late pregnancy may involve
bones, teeth, eyes, cranial nerves, viscera, skin, and
mucous membranes
 Hutchinson’s triad includes interstitial keratitis of the
cornea, eighth nerve deafness, and dental abnormalities,
including Hutchinson’s incisors and mulberry molars

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Laboratory and
Diagnostic Findings
 T. pallidum has never been cultured successfully
on any type of medium and is difficult to stain for
microscopic examination
 Definitive diagnosis of syphilis has been made from
microscopic examination of fresh lesion exudates during
the primary and early secondary stages using positive
dark-field microscopic examination
 Definitive diagnosis of oral lesions by this method is
difficult because other species of Treponema are
indigenous to the oral cavity

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Laboratory and Diagnostic
Findings (cont’d)
 Standard screening tests for syphilis consist of
the Venereal Disease Research Laboratory
(VDRL) slide test, the rapid plasma reagin (RPR)
test, and the automated reagin test (ART)
 These indirect, nontreponemal serologic tests are
designed to detect the presence of an antibody-like
substance called reagin that is produced when T.
pallidum reacts with various body tissues
 They are equally valid
 A disadvantage of reaginic tests is the occasional biologic
false-positive result that can occur

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Findings (cont’d)
 Nontreponemal tests produce titers that usually
correlate with disease activity
 In primary syphilis, nontreponemal tests usually revert to
negative within 12 months after successful treatment
 In secondary syphilis, up to 24 months may be required
for the patient to become seronegative
 Occasionally, a patient will remain seropositive for life or
will test positive in the presence of an associated
infection or condition (false-positive)
 With tertiary syphilis, many patients remain seropositive
for life

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Findings (cont’d)
 Treponemal tests are designed to detect the
specific antibody produced against treponemes
that cause syphilis, yaws, and pinta
 These test are more specific than reaginic tests but less
sensitive, and are typically performed after a positive
VDRL or RPR
 A newer three step “reverse” algorithm has been adopted
with the intent to better capture those with a past history
of infection and early stage disease
 A treponemal immunoassay is performed first and if
reactive is followed, a qualitative non-treponemal test.
 If this second test is negative, a final quantitative non-
treponemal test is performed

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Medical Management
 Testing for concomitant HIV infection and the
diagnosis/management of infection in the sexual
partners is recommended
 Parenteral injection of long-acting benzathine penicillin
remains the recommended treatment for primary,
secondary, or early latent syphilis
 A more intensive regimen is indicated for those with late
latent or tertiary syphilis
 If results prove the disease or suggest that syphilis is
highly probable, then infants should be treated with IV
penicillin

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Medical Management (cont’d)
 The first-line drug for patients allergic to penicillin
(except for pregnant patients) is oral doxycycline
 Desensitization to penicillin is recommended for pregnant
patients allergic to penicillin.
 Patients with primary or secondary syphilis who are
otherwise immunocompetent should be retested at 6 and
12 months to monitor for seroconversion.
 HIV-infected patients, and those with late latent or tertiary
syphilis require more intensive or longer surveillance
respectively.
 The Jarisch-Herxheimer reaction is an acute febrile
reaction that is frequently accompanied by chills,
myalgias, and headache that occurs within 24 hours

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 Lesions of untreated primary and secondary
syphilis are infectious, as are the patient's
blood and saliva
 Even after treatment starts, absolute effectiveness
cannot be determined except through conversion of
the positive serologic test to negative
 Necessary dental care may be provided with
adherence to standard precautions, unless oral
lesions are present

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Oral Manifestations
 Oral syphilitic chancres and mucous patches
are usually painless, unless they become
secondarily infected. Both lesions are highly
infectious
 Oral manifestations of secondary syphilis are highly
variable and include single or multiple lesions like:
mucous patches, maculopapular lesions, erosions,
ulcerations, and more
 The intraoral mucous patch is often asymptomatic
and appears as a slightly raised greyish plaque and
may involve multiple oral sites

46
Oral Manifestations (cont’d)
 The oral gumma of tertiary syphilis is rare
 Typically presents as a solitary lesion commonly
involving the tongue and palate, which may be
exophytic, indurated, and with surface ulceration
 Palatal gummas may erode bone and perforate into
the nasal cavity or maxillary sinus
 Oral manifestations of congenital syphilis include
peg-shaped central incisors with notching of the
incisal edge (Hutchinson's incisors) defective molars
with multiple supernumerary cusps, a high narrow
palate, and perioral rhagades

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 Manifestations of syphilis can mimic
malignant neoplasms, however the evidence
for syphilis as a causative agent for cancer is
not clear
 Syphilis has been identified as a risk factor for oral
squamous cell carcinoma, particularly of the tongue
in patients with syphilitic glossitis associated with
tertiary syphilis

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Genital Herpes Simplex
Virus Infections
 Genital herpes is an incurable and painful
infection involving the anogenital region
caused by one of two closely related types of
herpes simplex virus (HSV) type 1 and type 2
 The disease consists of acute and recurrent
phases and is associated with high rates of
subclinical infection and asymptomatic viral
shedding

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Epidemiology
 Genital herpes is an important STD
worldwide
 Seroprevalence for genital HSV infection is
challenging to assess
 HSV-2 antibodies correlate to a sexual/genital
transmission, however it is difficult to differentiate
between oral versus genital HSV-1 infection
 A conservative estimate for genital herpes caused
by HSV-1 infection is 50%, and this translates to a
global genital HSV seroprevalence (for 15-49 year
olds) estimated of at least 544 million

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Epidemiology (cont’d)
 The CDC reports approximately 24 million
Americans have HSV-2 infection, with greater
than 750,000 new infections annually
 Estimates do not include HSV-1 infection, and data
from another study reported seroprevalence for
HSV-1 and HSV-2 in the general US population of
53.9% and 15.7% respectively from 2005-2010
 HSV-2 seroprevalence is approximately twice as
high for women (22%) versus men (11%), and
almost three times as high for non-hispanic blacks
(56%) as whites (21%)

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Etiopathogenesis
 HSV belongs to a family of eight human
herpesviruses that includes cytomegalovirus,
Epstein-Barr virus (EBV), varicella-zoster
virus (VZV), human herpesvirus type 6 (HHV-
6), human herpesvirus type 7 (HHV-7), and
Kaposi sarcoma-associated herpesvirus
(HHV-8)
 HSV-1 is the causative agent of most herpetic
infections that occur above the waist, especially on
the mucosa of the mouth, nose, eyes, brain, and
skin

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 The majority of primary infections with HSV-1
are subclinical and thus are never known to
the infected person
 Infection with HSV-1 is extremely common; most
adults demonstrate antibodies to this virus
 Transmission to others usually occurs through close
contact, through transfer of infective saliva such as
touching, kissing, or via oral sexual contact
 HSV may also be transmitted to a newborn from an
infected mother (neonatal herpes)
 During the initial exposure, epithelial/epidermal and other
permissive cells are “invaded” and viral replication occurs

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 With cellular destruction comes inflammation
and increasing edema, which form, that
progress to fluid-filled vesicles. The vesicles
rupture, leaving an ulcerated surface that
exposed to the air will crust over
 In primary infection, progeny enter the ends of local
peripheral neurons and migrate up the axon to the
regional ganglia, becoming a latent infection
 The virus can, migrating down the axon, and can
produce a recurrent infection with lesions similar to
the primary infection, albeit typically less severe and
more localized

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 Clinical manifestations of genital herpes are
divided into primary and recurrent infections
 The clinical course of the primary infection varies,
but lymphadenopathy and viremia are prominent
 The infection is contained within the immune system
and runs its course within 10 to 20 days
 Newly acquired genital infections may be
symptomatic in about two-thirds of HSV-1, and 40%
of HSV-2 infections, respectively

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 After an incubation period of 2 to 10 days, the
lesions of primary genital herpes may appear
 In women, both internal and external genitalia may be
involved, as well as the perineal region, and the skin of
the thighs and buttocks
 In men, the external genitalia may be involved, as well
as the skin of the inguinal area
 Lesions in moist areas tend to ulcerate early, are
painful, and may cause dysuria
 Painful regional lymphadenopathy accompanies
infection, along with headache, malaise, myalgia, and
symptoms of fever, subsiding in about 2 weeks, with
healing occurring in 3 to 5 weeks

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 Outbreaks of recurrent genital herpes occur 2
to 6 times per year and are generally less
severe than the primary infection
 HSV-2 is more efficient in reactivating, and genital
recurrences in those infected by HSV-2 are about 4
times as likely as those infected with HSV-1
 Immune suppression increases the risk for more
frequent and severe recurrences
 A prodrome of localized itching, tingling, paresthesia,
pain, and burning may be noted and is variably
followed by a vesicular eruption

57
 HSV-1 and HSV-2 lesions are highly
infectious with recurrent herpes and therefore
can be transmitted to other individuals or to
other sites on the patient
 The infectious period of herpetic lesions is of uncertain
length, but positive viral cultures are detected most often
from stages prior to crusting
 One should assume that all herpetic lesions (i.e., papular,
vesicular, pustular, and ulcerative) prior to completion of
crusting are infectious
 Clinical manifestations subside in about 2 weeks, and
healing occurs in 3 to 5 weeks

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 Outbreaks of recurrent genital herpes
typically occur 2 to 6 times per year and
generally are less severe and more localized
than the primary infection
 A prodrome of localized itching, tingling, paresthesia,
pain, and burning may be noted and is variably
followed by a vesicular eruption
 Healing occurs in 10 to 14 days
 Between recurrences, infected persons intermittently
shed virus from the anogenital region which can also
lead to transmission

59
Laboratory and Diagnostic Findings
 Samples taken from active genital lesions may
be tested in various ways to confirm viral types
 Cytopathological testing is typically not recommended
 Viral culture is slow (about 5 days), expensive, and
technique-sensitive
 Real-time PCR assays are accurate, fast, less technique-
sensitive, provide quantitative results, and can be used to
assess asymptomatic viral shedding
 DIF is a rapid test, but can only be used on rich fresh
samples—ideally within 24 hours of manifestation
 Serology to detect HSV-1 or HSV-2 IgG is reliable to
show past infection

60
Medical Management
 Evidence-based management strategies for
genital herpes are related either to the
treatment of acute outbreak, or to the
prevention of recurrent infections
 For those presenting with a first clinical episode,
treatment includes oral antiviral therapy with either
acyclovir (topical), famciclovir, or valacyclovir
 Use of systemic antiviral drugs can shorten the
duration, frequency, and symptoms of outbreaks and
can reduce the frequency of asymptomatic shedding
and the risk of transmission

61
 Antiviral agents do not eliminate the virus
from the latent state, however, nor do they
affect subsequent risk, frequency, or severity
of recurrence after drug use is discontinued
 Antiviral drugs are most effective when given for
prevention at least 1 day within appearance of
symptoms, whether for primary or recurrent disease
 Daily suppressive antiviral therapy can be
implemented for patients with frequent recurrences

62
 Current antiviral treatment recommendations
by the CDC are directed toward primary,
recurrent, and suppressive herpes therapy
 These protocols may also be used for oral infections
 Intravenous antiviral agents (acyclovir, cidofovir and
foscarnet) are reserved for severe or complicated
infections, and perhaps for immune-suppressed
patients
 Despite extensive research, there is currently no
effective vaccine for HSV infection

63
Dental Considerations and
Oral Manifestations
 Genital herpes may rarely be transmitted
from genital sites to the oral cavity
 HSV-induced lesions in oral and perioral tissues are
infectious at the papular, vesicular, and ulcerative
stages; elective dental treatment should be delayed
until lesions have healed
 Dental manipulation during infectious stages poses
risks of (1) inoculation to a new site on the patient,
(2) infection to the dental care worker, and (3)
aerosol or droplet inoculation of the conjunctivae of
the patient or of dental personnel

64
Dental Considerations and
 Of particular concern to dentists is herpetic
infection of the fingers or nail beds contracted
by dermal contact with a herpetic lesion of the
lip or oral cavity of a patient
 A “herpetic whitlow,” or a herpetic paronychia is
serious, debilitating, and recurrent
 Asymptomatic HSV shedding at oral or non-oral
sites can trigger erythema multiforme, a
mucocutaneous eruption characterized by “target”
papules and ulcers that result from an immune
response to the virus

66
Recommendations for Patients
with Herpes Simplex Infections
• Patients with active lesions should not be seen in
the dental office. Appointments should be
rescheduled.
• Antibiotics and corticosteroids will not work in the
treatment of HSV
• Antiherpetic drugs:
• Acyclovir sodium (Zovirax)- cream or tablet form
• Docosanol (Abreva)- OTC cream for herpes labialis
• Orabase-B- topical anesthetic to reduce pain/itching

67
Infectious Mononucleosis
 Although not classically defined as an STD,
transmission of infectious mononucleosis (IM)
occurs through intimate personal contact
 IM is caused, in at least 90% of cases, by a primary
Epstein-Barr virus (EBV) infection
 Children, adolescents, and young adults are most
commonly affected and transmission of the virus
occurs primarily by way of the oropharyngeal route
during close personal contact
 IM, associated with lymphocytosis, produces fever,
sore throat, and lymphadenopathy

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Epidemiology
 More than 90% of adults worldwide have
been infected with EBV
 EBV increases during childhood, with the highest
rates in non-hispanic blacks aged 15-19 years
 The peak age of acquisition in the United States is
reportedly 15 to 19 years old with no gender
predilection
 Having numerous sexual partners increases the risk
for acquisition of EBV
 Only about 25% of teenagers who are infected with
EBV develop IM

69
Etiopathogenisis
 EBV is a lymphotropic herpesvirus that is
transmitted primarily through close personal
contact and exposure to infected saliva and
oropharyngeal secretions
 A prodromal period of 3 to 5 days precedes the
clinical phase, which lasts 7 to 20 days
 During the prodromal phase, the virus infects
oropharyngeal epithelial cells and spreads to B
lymphocytes in the tonsillar crypts

70
Etiopathogenisis (cont’d)
 Infected B lymphocytes circulate through the
reticuloendothelial system, triggering a marked
lymphocytic response
 In infectious mononucleosis, large, reactive lymphocytes
expand from 1%–2% to 10%–40% of the circulating white
blood cells
 These expanded T lymphocytes are reactive to the EBV-
infected B lymphocytes
 The combination of reactive lymphocytes, the cytokines
they produce, and the B cell–produced (heterophile)
antibodies directed against EBV antigens contributes to
the clinical manifestation of the infection

71
 Signs and symptoms
 Infectious mononucleosis usually is
asymptomatic when found in children; however,
about 50% of infected young adults develop
symptoms
 Fever, sore throat, tonsillar enlargement,
lymphadenopathy, malaise, and fatigue are the
predominant features
 About a third of patients demonstrate palatal petechiae
during the first week of the illness, and about 30% of
patients develop an exudative pharyngitis

72
Laboratory and
Diagnostic Findings
 An IM diagnosis cannot be made via clinical
examination alone. Laboratory testing is
necessary for confirmation
 A white blood cell count demonstrating
lymphocytosis with blood smears revealing atypical
“reactive” lymphocytes is highly predictive
 Other lab testing includes the non-specific
heterophile antibody test, specific enzyme
immunoassay antibody tests, and polymerase chain
reaction

73
Findings (cont’d)
 Symptomatic patients in whom a heterophile
antibody test is negative should be retested in
7 to 10 days because this test can be
insensitive during the first week
 If the second test is negative, tests for viral capsid
antigen (VCA) IgG and VCA IgM antibody and EBV
nuclear antigen (EBNA) should be performed
 If test results are positive, the patient has
heterophile-negative infectious mononucleosis
 Once EBV-associated IM is diagnosed, EBV copy
numbers in the blood can monitor severity and
infection progression

74
Medical Management
 IM is largely the result of the immune response to
EBV and there are no pharmacotherapies for it
 Treatment of patients remains symptomatic and
supportive with bed rest, acetaminophen or nonsteroidal
anti-inflammatory agents for pain control, and gargling and
irrigation with saline solution or lidocaine to relieve throat
symptoms
 Vigorous activity is to be avoided for at least 3 weeks to
reduce the risk of rupture of an enlarged spleen
 Most patients return to normal activities within a month.
 Despite active research, there are currently no vaccines
to prevent IM

75
 Patients with IM may come to the dentist
because of oral signs and symptoms and should
be referred to a physician for evaluation and
treatment
 Routine dental treatment should be delayed for
about 4 weeks until the patient has recovered

76
Oral Manifestations
 Patients (particularly adolescents) presenting
with palatal petechiae, enlarged tonsils, a
pharyngitis with tonsillar exudate, and with
cervical lymphadenopathy should raise suspicion
of IM
 Patients with a history of IM may be at risk for
developing EBV-associated Hodgkin’s and non-
Hodgkin's lymphomas
 These lymphomas may manifest as persistent
cervical lymphadenopathy or oral cavity lesions

77
Genital Warts/
Human Papillomavirus Infection
 Human papillomaviruses (HPVs) are small,
double-stranded, nonenveloped DNA viruses
that infect and replicate in mucosal and
cutaneous sites
 More than 120 genotypes of HPV have been
identified, and more than 40 types are known to be
sexually transmitted and to affect anogenital
epithelium
 Each HPV subtype exhibits preferential anatomic
sites of infection and a propensity for altering
epithelial growth and replication

78
Genital Warts/Human
Papillomavirus Infection (cont’d)
 The spectrum of disease that is induced is
dependent on the type of HPV infection,
location, and immune response
 Low-risk HPVs (HPV-6, -11) produce benign lesions
(involving genital and other non-genital skin and
mucosal sites)
 High-risk HPV types (HPV-16, -18) are strongly
associated with intraepithelial lesions and carcinoma
of the cervix, vagina, and anus
 HPV-16 is also strongly associated with
oropharyngeal cancer (base of tongue and tonsils)

79
Epidemiology
 Genital warts are the most common STDs
with a global annual incidence estimated from
100 to 200 per 100,000
 An estimated 80 million people in the U.S. with an
active genital HPV infection and more than 14
million new infections occurring annually
 At least 50% of sexually active adults will acquire an
HPV infection during their lifetime
 Genital warts are common in both sexes, and the
highest rates of infection occur between the ages of
19 and 26 years

80
Epidemiology (cont’d)
 The lifetime number of sexual partners is the
most important risk factor for the development
of genital warts
 By age 50, more than 80% of women will have
acquired genital HPV infection
 The infection is more common among African
American women than white women
 Based on data from 2008-12, there are
approximately 31,000 HPV-associated cancers
diagnosed annually in the U.S.

81
Etiopathogenesis
 Genital HPV can be transmitted by direct
contact during sexual contact or passage of a
fetus through an infected birth canal, or by
autoinoculation
 The virus enters the epithelium/epidermis through
microtears and infects the basal cell layer. Once the
virus is intracellular, it increases the turnover of
infected cells
 Genital lesions usually appear after an incubation
period of 3 weeks to 8 months

82
 Anogenital warts are primarily external, although
they may be found intra-anally, intra-vaginally, or
involving the cervix and urethral meatus
 Externally, they have a variable clinical appearance,
ranging from small multiple confluent sessile papules to
grossly exophytic papillary, or warty cauliflower-like
lesions measuring up to several centimeters in diameter
 In men, these growths may be found on the penis,
scrotum, pubic region, and anal/rectal areas
 In women, genital warts are commonly found on moist
areas on the labia minora and vaginal opening

84
Laboratory and
Diagnostic Findings
 HPV does not grow in cell culture, and serologic
tests are not routinely performed
 Therefore, lesions of condyloma acuminatum should be
biopsied and examined microscopically, if the clinical
diagnosis is uncertain
 The microscopic appearance consists of a sessile base,
with raised epithelial borders, a thick spinous spinosum
layer (acanthosis), hyperkeratosis, and often with the
presence of koilocytes
 Identification of HPV genotype is typically achieved with
the use of commercial DNA and RNA in situ hybridization
kits to detect HPV

85
Medical Management
 As with all STDs, treatment should include
the patient's sexual partner to avoid re-
infection and protective activities (for
example, abstinence or use of condoms) is
importance to reduce transmission. Without
treatment, lesions may enlarge and spread,
although spontaneous regression can occur

86
 Genital Warts
 Strong evidence supports the use of a number of
regimens to lead to clearance of warts, reduce
recurrence, and prevent further transmission
Surgical/ablative techniques or the administration of anti-
proliferative or immunomodulatory agents
Ablative techniques, including scalpel excision,
electrosurgery, laser removal, cryotherapy, photodynamic
therapy
Chemical destruction with trichloroacetic acid,
bichloroacetic acid, or potassium hydroxide
Non-destructive topical agents, including podophyllotoxin,
podophyllin, imiquimod, sinecatechins, cidofovir, and 5-
fluorouracil

87
 Cancer
 Management of lesions diagnosed with low- or high-
grade anogenital squamous intraepithelial disease or
squamous cell carcinoma generally involves surgery
with or without radiation therapy, chemotherapy, or
targeted therapy
 A major advance occurred in 2006 with the introduction
of the quadrivalent HPV vaccine (Gardasil), which
covers HPV genotypes 6, 11, 16, and 18
 Gardasil is 95-100% effective in preventing infection
and is approved for use in females aged 9 to 26 years,
and males aged 11 or 12

88
 Cancer (continued)
 A new nonavalent HPV vaccine (Gardasil 9) has
been introduced which covers 5 additional
oncogenic genotypes (31, 33, 45, 52, and 58)
 Within 6 years of the introduction of the quadrivalent
vaccine, the prevalence of HPV-6, 11, 16, 18
infection in young females has shown a significant
reduction (a 64% decrease in the 14-19 year old
group, and a 34% decrease in the 20-24 year old
group)

89
Oral Manifestations and
 Oral condylomata acuminatum commonly
occur as solitary or multiple lesions on the
ventral tongue, gingivae, labial mucosae, and
palate
 Oral warts in HIV infected patients,
predominantly in the MSM population, may
present as solitary lesions or as clusters of
multiple lesions that may be florid in their
presentation, and which can be esthetically
obtrusive

90
Dental Considerations (cont’d)
 Not all oral warts are transmitted sexually
 When detected during a routine examination, oral
healthcare providers should elicit a careful history to
assess the likely mode of transmission
 Condylomata in children raises the suspicion of
sexual abuse, particularly when especially when
other modes of transmission have been ruled out
 Failure to report signs of an STD to state health
officials is a legal offense in some states

91
Dental Considerations (cont’d)
 Oral warts typically present little risk for
transmission to the oral healthcare team
 Solitary oral warts may be surgically excised and
submitted for histopathology
 Lesions can be surgically excised or removed by
electrocautery or laser
 Clearance of warts with the use of topical, intra-
lesional or systemic agents such as podophyllin,
imiquimod, cimetidine, interferon, or cidofovir have
been reported, although adverse effects are possible

92
Supplemental Information
• https://www.cdc.gov/std/hpv/stdfact-hpv.htm

93
Questions to Ask Patients with a
Sexually Transmitted Disease
• Do you have a STD or venereal disease?
• If so, what disease do you have?
• How long have you had this disease?
• Are you taking any medications to treat this
disease?
• Are you currently experiencing any signs or
symptoms of this disease?

94
Summary
 The dental management of patients with an
STD begins with identification
 This is not possible in every case as some patients
will not provide a history or may not demonstrate
significant signs or symptoms suggestive of disease
 The inability of clinicians to identify potentially
infectious patients applies to other diseases as well,
such as HIV infection and viral hepatitis
 Therefore, it is necessary for all patients to be
managed as though they were infectious

95
Summary (cont’d)
 The CDC, has published recommendations
for standard precautions to be followed for
preventing cross-infection in dentistry
 Strict adherence to these recommendations will
eliminate the danger of disease transmission
between the dental team and patients
 New cases of syphilis, gonorrhea, and AIDS should
be reported to the local/state health department
 Reasonable suspicion of sexual abuse in children,
such as the identification of oral condylomata,
should also be reported

96
Summary (cont’d)
 Although presence of genital condylomata
acuminata does not affected dental
management, oral warts are infectious, and
standard precautions apply during oral dental
procedures
 The presence of oral lesions necessitates referral to
physician to rule out genital lesions in the patient or
any sexual partner
 Excisional biopsy or antivirals is recommended for
HPV oral lesions

97
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Chapter 13 STDs

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