Human Papilloma Virus

Infections
David Tindle, BS, DDS, MS, FAGD, DABOM
University of Michigan
 Describe the difference between HPV infection
and HIV infection

List the four modes of transmission of HPV

List the two low-risk and two high-risk HPVs

described in this chapter, their associated
Learning lesions, and pathogenesis

Objectives
Explain the difference between oral and
oropharyngeal cancer as they relate to HPV

Describe the concerns regarding salivary testing

for HPV and clinical considerations regarding
questioning patients about HPV exposure
 See the difference?

 Condyloma acuminatum  Squamous papilloma

Photos from Oral Pathology: a comprehensive atlas and text 8th ed: Woo, Sook-Bin
 Importan
Genital Warts/ t
Concept!
Human Papillomavirus Infection Understa
nd the
Human papillomaviruses (HPVs) are DNA differenc
e
viruses that infect and replicate in mucosal and between
cutaneous sites epithelial
 They are epithelial viruses with the disease virus and
blood
localized to the area of infection borne
 This is unlike HIV which is a systemic blood borne virus
infection
pathogen. s
 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
 Genital Warts/Human
Papillomavirus Infection (cont’d)
 The spectrum of disease that is induced is Usually these are
dependent on the type of HPV infection, exophytic such as a
papilloma
location, and immune response
 Low-risk HPVs (HPV-6, -11) produce benign
lesions (involving genital and other non-genital Usually not visible
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)
What does this mean?

 Common oral exophytic HPV lesions, such as squamous

papilloma or verruca, are not considered pre-malignant!
Instead they are classified as benign fibro-epithelial lesions
 Pre-cancerous or malignant lesions of HPV tend to be either
invisible to the eye or appear as a flat, leukoplakia in the oral
cavity
 Note the difference between oral cancer and oropharyngeal
cancer. Oral cancer does not have a strong association with
HPV. Oropharyngeal (tonsils, base of tongue, oropharynx)
cancer does have an association and those with HPV+
oropharyngeal cancers have a better prognosis than those with
HPV- oropharyngeal cancers
 HPV16 is strongly associated with base of tongue and tonsillar
cancers
 Epidemiology

 Genital warts are the most common STDs

with a global annual incidence estimated from
100 to 200 per 100,000
 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
 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
 Etiopathogenesis

 Genital HPV can be transmitted by direct

contact during sexual contact or vertical
transmission during passage of a fetus
through an infected birth canal, through
saliva, 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
Clinical Presentation

 Anogenital warts are primarily external, although they may

be found intra-anally, intra-vaginally, or involving the
cervix and urethral meatus – they can infect the oral
epithelium via oral to anal or oral to genital contact!
 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
 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 – this is primarily for
analyzing oropharyngeal cancers to determine HPV
involvement or not. It is not used for oral biopsy
specimens
 Medical Management

 As with all STDs, treatment should include

the patient's sexual partner to avoid re-
infection and protective activities to prevent
spread or recurrence such as using condoms.
 Medical Management (cont’d)

 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
 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
Medical Management (cont’d)

 HPV 9 valent vaccine (Gardasil) which includes low

risk HPV genotypes 6, 11, high risk types 16 and
18 along with 5 others
 Gardasil is 95-100% effective in preventing
infection and is approved for use in persons ages 9
to 45. It is recommended for all persons to be
vaccinated at age 11 o 12.
Oral Manifestations and
Dental Considerations
 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

“Men who have Sex with Men”

Photos from Oral Pathology: a comprehensive atlas and text 8 th ed: Woo,
Sook-Bin
 Oral Manifestations and
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
 Oral Manifestations and
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
podophyllum, imiquimod, cimetidine, interferon, or
cidofovir have been reported, although adverse
effects are possible
Salivary diagnostic testing for
HPV
 Marketed under brand OraRisk
 Salivary rinse collection
 Good specificity at 92% (few false positives) – if you don’t
have HPV it usually gives a negative test
 Not so good sensitivity at 72% (false negatives) (about
27% of the patients with HPV won’t show up positive!
 So, not FDA approved, or ADA recommended
 I don’t use it on my patients either
Clinical Considerations
You need to understand this!

 Should I ask my patient if she is HPV positive? No. A positive

result on a Pap smear, while very concerning, does not increase oral
cancer risk. This is because it is a localized infection of the cervical
epithelium. So, this does not increase her oral cancer risk.
 Should I ask my male/female patient if his/her wife or partner
has had a HPV+ Pap smear? No, at least not at this time. Because we
don’t have an evidence base to support an increased risk for oral cancer
among spouses of HPV+ women. Also, most adults will clear the HPV
infection within 2 years. Additionally, you would be making an intrusive
assumption about the couple’s sexual practices since oral-genital
contact would be necessary for transmission.
 Summary

 Oral warts are infectious, and standard

precautions apply during oral dental
procedures
 Excisional biopsy or antivirals is recommended for
HPV oral lesions
 Reasonable suspicion of sexual abuse in children,
such as the identification of oral condylomata,
should also be reported
 Salivary diagnostic testing for HPV is not currently
recommended