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self-study
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2017
course
#1
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The Ohio State University College of
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2017
course
#1
HPV-related Oropharyngeal
Carcinoma
Learning Objectives:
1. Learn key points about HPV-related OPSCC
2. Describe OPSCC prevalence and routes of
acquisition
3. List and describe subtypes of HPV-related OPSCC
4. Identify the warning signs and methods of
diagnosis, as well as disease treatment
5. Test knowledge by reviewing the True/False
questions
This is an OSDB Category B – Supervised selfinstruction course
written by
Vimi Mutalik, BDS, MDS
INTRODUCTION
edited by
Sydney Fisher, BS
Nick Kotlar, BS
release date
February 27, 2017
(8:30am EST)
The purpose of this CE self-study is to review the acquisition,
prevalence, diagnosis and treatment of HPV-related
oropharyngeal carcinomas, as well as disease subtypes and
warning signs/symptoms. This CE self-study will also address
prevention methods and the relationship between HPV and
OSCC.
last day to take the
course at no charge
March 31, 2017
4:00pm EST
Page 1
What is HPV-related OPSCC?
The head and neck squamous cell carcinomas (HNSCC) are a heterogeneous
group of neoplasm originating from various anatomic regions namely the oral cavity,
oropharynx, hypopharynx, larynx and nasopharynx. Increased incidence of Human
Papilloma Virus (HPV) as a cause of cancer in the head and neck region has made it
important to analyze different subsites intraorally with caution.
Although we refer to oral cancers in general, anatomically they are divided into
oral cavity and the oropharynx. The cancers originating from the two anatomic sites, oral
cavity and oropharyngeal region causes oral squamous cell carcinoma (OSCC) and
oropharyngeal squamous cell carcinoma (OPSCC) respectively.
Table 1: Features differentiating oral (OSCC) and oropharyngeal cancers
(OPSCC)
Parameters
Site
Oral cancer
Anterior oral mucosa
Etiology
Primary
Clinical
features
Smoking, alcohol
Incidence
Nodal
involvement
Sex
predilection
Social history
Synergistic
effect
Prognosis
Oropharyngeal cancer
Base of tongue, tonsils,
posterior oral mucosa
Increased sexual partners, HPV
White plaque, ulcer
Enlarged lymph node in neck,
dysphagia
Decreasing
Present
Males common (3:1)
Increasing
Present and may be the only
sign of the disease
Males (5:1)
Smoking (80-90%)
Alcohol
Smoking (50-65%)
Alcohol not a significant factor
40% survival rate
80% survival rate
Page 2
The cancers originating from these two anatomic sites (OSCC and OPSCC)
vary considerably in terms of their statistics, etiologies, clinical signs and symptoms
and response to treatment. HPV is now thought to be a risk factor in causation
OPSCC (referring to posterior regions of the mouth) and not OSCC (common in
anterior regions of the mouth).
The discussion in this course is focused mostly on HPV-positive OPSCC
which includes cancers from the base of tongue, tonsillar and pharyngeal wall. The
OPSCC that are HPV-positive have risk factors related to sexual behavior, whereas
HPV-negative cancers are strongly associated with tobacco and alcohol use.
What are the key facts about HPV infection?
Human papilloma virus (HPV) is the most common cause of sexually
transmitted disease in the United States. HPV infection is very well-known in the
causation of cervical cancers. However, it has been linked to various other cancers
as well. In United States, new cases of cervical cancer have declined over the past
30 years because of increased use of Pap test, cervical smears or Pap smears.
These tests enable professionals to identify early alterations in mucosa and are
more curable than the invasive cancers.
Although the rate of cervical cancer has been decreasing in women, the
cancer on the back and sides of the throat, tonsils and base of tongue have
increased significantly in men over the past few years.
HPV has been thought to infect 90% of the U.S. population. About 12,000
Americans between ages of 15 to 24 are infected with HPV daily and about 26
million Americans have oral HPV infection on a given day. This definitely does not
mean that all these patients develop OPSCC. In a vast majority of patients, the
infection is cleared away within two years with their immune response and may not
cause any health issues.
There are nearly 200 strains of HPV; however, most of them do not cause
cancers. Hence they are categorized into high-risk and low-risk subtypes. The lowrisk strains are associated most commonly with the causation of benign, noncancerous, genital and nongenital warts and the high-risk strains cause
precancerous lesions which subsequently progress to cancer. The high-risk strains
like HPV 16 and 18 are most commonly associated with occurrence of
oropharyngeal cancers. Among them, HPV 16 is greater than 90% of times
associated with oropharyngeal cancer.
Page 3
HPV facts continued…
The Human Papilloma Virus (HPV) is a double stranded DNA virus that infects
the epithelial cells of the skin and mucosa. These viruses have special affinity
towards epithelium and are called epidermo-tropic. The mucosal surfaces that are
moist like the throat, tongue, tonsils, vagina, cervix, vulva, penis and anus are more
susceptible for development of diseases from this virus. Hence these viruses have
also a major role in development of cervical, anal and penile cancers. When the virus
contacts the epithelial surface it causes changes (koilocytic or viral induced changes)
in the infected cells.
The unique nature of transitional mucosa and the invaginations in the mucosal
surface in the tonsils enables virus capture and makes it a preferential site for HPV.
Moreover, the genetic features of HPV 16 facilitate an ideal environment for survival
of these oncogenic (cancer-causing) organisms. Although HPV-positive and HPVnegative subtypes OPSCC exists, HPV is detectable in majority of the patients with
oropharyngeal cancers. Therefore, in the oropharyngeal region the HPV-positive
cases of OPSCC definitely outnumber the HPV-negative OPSCCs.
Table 2: HPV facts sheet
HPV is highly associated with oropharyngeal squamous cell carcinoma (OPSCC),
but not oral squamous cell carcinoma (OSCC)
Oropharyngeal squamous cell carcinoma (OPSCC) can be HPV-positive or HPVnegative. But the prognosis for the HPV-positive cases is better.
Not all patients who have high-risk HPV in saliva develop oropharyngeal
carcinoma.
If you get HPV infection, you may or may not develop a precancerous or
cancerous lesion.
HPV, a primary cause for oral cancer (OSCC), lacks enough scientific evidence.
HPV vaccines are safe and effective.
Page 4
What is unique about HPV infection and OPSCC?
The HPV-induced OPSCC have
many unique features that distinguishes
them from the conventional OSCC.
Some studies indicate that the timing
between the first exposure to HPV and
the development of oropharyngeal
cancer approximately exceeds 19 years.
Oropharyngeal cancers (HPVinduced) present with very subtle clinical
signs/symptoms and at most times the
patient is unaware of it. Even the
clinicians may find it hard to discover
because the symptoms can be very
elusive and painless. This is the main
reason why OPSCC are usually
identified at a later stage. Hence, it is
very important that a very thorough
examination is undertaken if the patient
reports persisting symptoms of a period
greater than two weeks. This is because
the clinical signs and symptoms vary
considerably from the obvious and
classical tobacco-induced OSCC.
Because the OPSCC have
predilection for posterior regions for the
mouth, accessibility to this area can be
difficult and the primary lesion can be
missed easily. Therefore, the tumor size
in OPSCC is usually greater and the
incidence of cervical and distant
metastasis is also higher compared to
OSCC.
On the other hand, in a vast
majority of patients, the infection is
cleared away within two years with
their immune response and does not
cause any health issues. Some
studies report that the infection with
high-risk HPV usually last for 12-18
months and is eventually cleared by
the immune system.
Persistent high-risk cases are
the ones that eventually lead to
development of malignancies or
cancers. On the other hand, if you get
HPV infection, you may or may not
develop
oral
pre-cancer
that
eventually leads to oral cancer. Also, if
you have a high-risk HPV infection, it
is a myth to consider that you will
definitely get HPV-induced OPSCC.
The molecular alterations of
HPV-positive head and neck cancer is
in sharp contrast with HPV-negative
head and neck cancers.
p53
mutations, downregulated p16 activity
and increased expression of pRb is
noted in HPV-negative head and neck
cancers. These differences in the
molecular profile indicate a lot about
tumor behavior and its response to
treatment.
Page 5
How common is OPSCC?
Head and neck cancers rank as the sixth most common cancer type worldwide. It
accounts for nearly 5% of the cancers around the globe. Out of the 650,000 cases
diagnosed worldwide each year, the annual mortality is about 300,000. Each year,
approximately 263,000 cases of oral cavity cancer and 135,000 cases of pharyngeal cancer
are diagnosed worldwide.
The national head and neck malignant tumor registries indicate oral cavity to be
the most predominant site, followed by larynx, hypopharynx, oropharynx, nose and
paranasal sinuses and nasopharynx. It is important to note that the OSCC are associated
with smoking and alcohol consumption, but the frequency of these cancers has declined in
the US over the past 20 years.
Figure 1: Incidence trends for Oral (OSCC) and Oropharyngeal (OPSCC) cancers
Source: Chaturvedi AK et al., JCO, 2013
Page 6
However, the OPSCC has been on the rise with an increase by 28%
during 1998 to 2004. In US, there is 225% increase in HPV-positive OPSCC
from 1984-2004.The annual rise in the number of cases is thought to be 70%
and this would surpass the annual numbers of cervical cancers.
The incidence of OPSCC is increasing in the economically developed
countries like US, UK, Europe and Brazil. By 2020, the overall OPSCC burden
in US is predicted to surpass cervical SCC. These changes have prompted
recent epidemiological work to study differences between HNSCC related to
tumor subsites and research on OPSCC is now taking a central position.
How is the disease acquired?
HPV usually involves the skin or the mucosal epithelium and causes
abnormal changes. In most cases, the body fights off the infection and the cells
that are infected get back to normal. When the body is unable to fight back
because of other coexisting factors (like systemic illness or comorbidities,
immunodeficiency status or habits like smoking), this virus can cause a range
of diseases like genital warts, oral squamous papilloma, condyloma
accuminatum and OPSCC.
HPV is a sexually transmitted disease, which is now thought to be
epidemic. Increased number of sex partners, open mouth kissing, practicing
oral sex (from mouth to genital) and having sex with a partner who has had
multiple sex partners are considered high risk factors. The incidence is greater
in males as compared to females. This has been attributed to several reasons
like a higher spread of infection through oral sex interaction on a woman. This
is also further proved by the fact that an increased incidence of these cancers
is seen more often in heterosexual men than homosexual men.
Another possibility could be that, men mount a less robust immune
response and are unable to protect themselves from the infection. A recent
case –control study also indicated that a high (>26) number of lifetime vaginalsex partners and 6 or more lifetime oral-sex partners are associated with an
increased risk of development of OPSCC. The risk is also high in female
partners with HPV-associated anogenital cancers and their male partners. On
the contrary, it is interesting to note that the incidence of HPV infection in longterm sexual partners is not increased beyond the level compared to the general
population.
Page 7
Figure 2: Indicating the level of exposure to risk factors.
Source: https://www.cdc.gov/std/hpv/stdfact-hpvandoropharyngealcancer.htm
A vast majority of these patients have been current /past smokers,
so smoking is thought to have a synergistic effect in the causation of these
cancers. Immunodeficiency (HIV) infection is also thought to increase the risk
for oral HPV infection. The immunodeficiency status is thought to increase the
persistence of the infection thereby leading to development of oral HPVrelated disease. Focusing on the various modes of transmission, the risk of
transmission from mother to child through saliva is questionable.
The recent increased incidence of this disease mirrors the societal
changes in sexual behavior that occurred in the developed world. The
incidence of oropharyngeal SCC (OPSCC) in the developed countries is
increasing as compared to Oral SCC (OSCC) in the developing countries. It is
reported that changes in the sexual behavior in the developed world have led
to an increase in the number of these OPSCC cases.
Page 8
What are the different subtypes?
Once acquired, the HPV infection goes through different
stages/status in the body which is discussed below:
• Transient carrier status: Infections clears with no lesions, positive for serum
antibody tests. It is the most common phase where the virus is present in mucosa
and is identified by advanced molecular tests like in situ hybridization (ISH) or
polymerase chain reaction (PCR). In majority of the cases, the virus is cleared within
1-2 years.
• Chronic carrier status: More frequently seen with high-risk subtypes and long
term immunosuppression. This is an uncommon phase. There can be persistence of
the high –risk virus and this has strongly been implicated in the development of
OPSCC. Chronic infection by HPV high-risk types confers to a 6- to 50-time
increased risk of developing HPV-positive oropharyngeal cancer.
• Benign lesions: Papilloma, verruca (warts), condyloma accuminatum.
• Premalignant lesions: Cases of koilocytic dysplasia or HPV induced dysplasia
have been described. However, the best described cases are in cervical dysplasia.
• Oropharyngeal cancer: Usually caused by HPV 16. About 90% of the patients
who have this high-risk type definitely have OPSCC in the appropriate clinical setting.
Page 9
What are the warning signs /symptoms of this disease?
Figure 3: Oropharyngeal squamous cell carcinoma (OPSCC) presenting as
an ulcero-proliferative growth in the posterior tonsillar area.
Courtesy: Dr. Carl Allen, Department of Oral Pathology, The Ohio State University. Columbus Ohio
OPSCC are commonly seen in Caucasian males, 50-60 years of age, less
exposed to tobacco and alcohol and with a relatively high socio-economic status.
Patients with these cancers usually present with nonspecific symptoms of throat
pain which is commonly seen during swallowing and abnormal sensation in the
throat. With advanced disease, there is a neck swelling (lymph node enlargement)
and dysphagia.
The primary lesion is usually located in the tonsillar fossa or in the base of the
tongue. Some patients also present with concern of ulcer on the throat, painless
tonsil, alterations in voice and ear ache. In most cases, the neck swelling will be the
primary concern since the nodal metastasis is aggressive. If the primary lesion is
small or in the absence of throat symptoms, a diagnosis of node metastasis from
carcinoma of unknown primary (CUP) is made.
Page 10
How do we diagnose this condition?
Although there are various chairside diagnostic tests to detect oral cancer,
HPV-induced OPSCC are best identified by a thorough recording or
medical/dental/social history from the patients, accompanied by visual and tactile
head/ neck examination. Comprehensive oral examination is a key in establishing
the diagnosis. Despite limited data showing improved survival, early detection of oral
cancer/ pre-cancer is considered an integral part of a comprehensive hard/soft tissue
examination that follows patient history and risk assessment.
An ulcer or sore throat that has not healed for 2-3 weeks, difficult or painful
swallowing, swollen but painless tonsil, recent change of voice/hoarseness, lump on
the neck and an ear ache are the guiding features towards a possible early detection
of these cancers. Like any diagnostic kit, this process of visual and tactile
examination may not be 100% effective, so it is important to pursue if the symptoms
have not resolved in 2-3 weeks’ time in order to arrive at a final diagnosis.
Figure 4: Site predilection for OPSCC
Source: http://headandneckcancerguide.org/wp-content/uploads/2013/02/19b_oropharynx1.jpg
Page 11
Diagnosis continued…
OraRisksm HPV by OralDNA® Labs and Quest Labs (2010) are
commercially available kits usually indicated if there are traditional risk factors like
sexual activity, family history of oral cancer, signs and symptoms of oral cancer and
presence of a suspicious oral lesion. It is usually noninvasive and easy to use. The
method is to gargle/swish with sterile saline for 30 seconds; expectorate into funneltop tube, ship, report. If the test is positive with no lesion, it is indicated to repeat the
test again in six months and if it’s positive, refer to oral surgery or the ENT
department.
On obtaining a biopsy from the primary site or a positive lymph node, these
tumors represent an early T and a higher N stage, exhibiting moderate to poor cellular
differentiation with basaloid/non-keratinizing morphology of tumor cells. The gold
standard for assessing the HPV infections is the molecular techniques: in situ
hybridization (ISH) or polymerase chain reaction (PCR). Both these techniques help to
detect HPV deoxyribonucleic acid (DNA). cDNA probe identifies the HPV DNA
sequence, but includes episomal DNA (transitory infections). Several biomarkers have
been useful; p16 is thought to be the most useful and reliable surrogate biomarker for
this. It is noteworthy to mention that that evidence of both HPV DNA and evidence of
viral DNA integration (p16+) are needed to diagnose an OPSCC as HPV-positive.
What is the treatment and prognosis for HPV
related cancers?
The protocol for treatment of OPSCC is mainly determined by the stage of the
disease. Single treatment modality, either surgery or radiotherapy is usually
recommended for early disease. The HPV-positive tumors have better response to
therapy. This is attributed to the presence of fewer genetic alterations, improved
immune response contributing to higher radio sensitivity and the absence of filed
cancerization effects. Moreover, the young age in association with less comorbidity
may also contribute to better treatment outcomes.
Comorbidities in the form of immunodeficiency states (HIV infection) or long
term history of smoking may alter the prognosis and appropriate response to therapy.
Tobacco smoking has been associated with worse prognosis in HPV-associated
oropharyngeal cancers. The risk of progression of the disease and an increase death
rate was directly proportional to the increased smoking history.
Overall, HPV-positive cancers are associated with improved 3-year survival,
80% versus 40% for HPV-negative cancers. These cancers have a 28% reduction in
risk of death and a 49% decrease in disease recurrence compared to the OSCC
which are treated aggressively and have dismal clinical outcome.
Page 12
How can we prevent HPV related
Oropharyngeal cancers?
Currently, two prophylactic vaccines, Gardasil (Merck, USA) and Cervarix
(GlaxoSmithKline, UK) are available and recommended for adolescent massimmunization. Recently, Gardasil-9, which is a nanovalent vaccine and protects
against nine strains of viruses, has been introduced. Since 2006, the federal drug
administration (FDA) has approved these vaccines for HPV, all of which render
protection against HPV 16 and 18. They are recommended for preteen girls and boys
at age 11 to 12 years. The CDC has also recommended this for candidates who did
not receive the vaccines when they were younger; including teen boys and girls,
women through age 26 and young men through age 21.
Both the vaccines are administered in a volume of 0.3mL intramuscularly.
After the initial dose, two more booster doses are given, one within 1 or 2 months
and another within 6 months. Although these vaccines have been very well-timed in
terms of prevention, some patients receiving these vaccines experience pain, fatigue,
redness, swelling, fever, GI symptoms, headache, dizziness, myalgia and arthralgia.
One of the most common adverse reactions noted is local erythema at the site of
injection. Rare cases of severe headache with hypertension, bronchospasm and
gastroenteritis have also been documented.
Gardasil has also been known to have caused infection, gastrointestinal
disorders, nervous system disorders, reproductive and breast disorders. Although
these vaccines have been effective, there is limitation in terms of their cost and
expenses, as well as preparation and preservation. These vaccines have been
designed specifically to reduce cervical cancer, but their effectiveness in minimizing
oropharyngeal cancer (OPSCC) is still debatable. Broader subtype coverage of
Gardasil-9 is expected to provide similar protection.
Studies have also indicated that a decade after the first vaccine have been
introduced, only 1 in 5 boys and 2 in 5 girls have been vaccinated. This number is
considered low when compared to the health policy target of 80 percent. In addition
to the vaccines, use of condoms, limiting the number of sex partners is also thought
to decrease the incidence of causing these cancers. To date, Cervarix and Gardasil
are considered “very safe” vaccines and have not been found to have a causal
relationship with any serious health concern in a majority of the patients.
Page 13
Can HPV cause OSCC in oral cavity?
Figure 5: Oral squamous cell carcinoma (OSCC) presenting as an ulcer in the anterolateral and
ventral portion of the tongue.
Courtesy: Dr. Carl Allen, Department of Oral Pathology, The Ohio State University. Columbus Ohio.
Comprehensive studies examining the site-specific prevalence of HPV
have indicated that it is present in lip mucosa, floor of mouth, palate, tongue etc., in
decreasing order of frequency. Since HPV DNA is present in reasonable subgroup of
OSCC, it is important to note that not all HPV-positive tumors can be considered to
be etiologically HPV driven.
Molecular studies analyzing the HPV DNA status could detect viral
oncogenes in only about 6-7% of the cases. This supports the notion that HPV is not
biologically active in a majority of these oral cancers and is simply a bystander of this
disease process. This separation is due to a different etiological process. This was
also proven by the fact that most of these tumors were p16-negative, which indicates
that the HPV was not transcriptionally active.
The overall estimation is that less than 5% of OSCC are HPV-related.
Hence, there is no consistent evidence of HPV as a risk factor for OSCC. Cases of
HPV-positive pre-cancer in oral epithelial dysplasia, which is also called koilocytic
dysplasia, has not been reported often. Studies also show that they have been both
high-risk HPV-positive and p16-positive.
A series of 20 cases of koilocytic dysplasia showed that the disease was
common in men, and presented as white or papillary lesions and usually on ventral
tongue. Among them, one recurred and one of them recurred (three times) in spite of
excision with clear surgical margins. Up to 67% of those patients were followed for
about 48 months and they had no evidence of disease. Hence the behavior off these
lesions is considered identical to the HPV-negative lesion.
Page 14
Abbreviations used:
• Head and neck squamous cell carcinoma (HNSCC)
• Oral squamous cell carcinoma (OSCC)
• Oropharyngeal squamous cell carcinoma (OPSCC)
• Human Papilloma Virus (HPV)
• Polymerase chain reaction (PCR)
• In-situ hybridization (ISH)
Educational Links:
Oral Cancer Foundation
http://oralcancerfoundation.org/understanding/hpv/hpv-oral-cancer-facts/
CDC
https://www.cdc.gov/std/hpv/stdfact-hpvandoropharyngealcancer.htm
UpToDate
https://www.uptodate.com/contents/human-papillomavirus-associated-head-andneck-cancer
About the Author
Vimi Mutalik, BDS, MDS
Vimi Mutalik completed undergraduate studies at Rajiv Gandhi University in India,
and continued on to receive a Masters in Oral Pathology from the same university.
Currently a second year resident in oral pathology at The Ohio State University,
Mutalik is studying HPV and its relation to oral pre-cancer. Future career plans are
to provide patient care through biopsy service and clinical pathology. Mutalik can
be reached at [email protected]
Neither I nor my immediate family have any financial interests that would create a conflict of interest or restrict
my judgement with regard to the content of this course
Page 15
References
• Jayaprakash V, Reid M, Hatton E, Merzianu M, Rigual N, Marshall J, Gill S,
Frustino J, Wilding G, Loree T, Popat S, Sullivan M. Human papillomavirus types
16 and 18 in epithelial dysplasia of oral cavity and oropharynx: a meta-analysis,
1985-2010. Oral Oncol. 2011 Nov; 47(11):1048-54.
• Liu H, Liu XW, Dong G, Zhou J, Liu Y, Gao Y, Liu XY, Gu L, Sun Z, Deng D. P16
Methylation as an Early Predictor for Cancer Development from Oral Epithelial
Dysplasia: A Double-blind Multicentre Prospective Study. EBioMedicine. 2015 Mar
23; 2(5):432-7.
• Miller CS, Johnstone BM. Human papillomavirus as a risk factor for oral squamous
cell carcinoma: a meta-analysis, 1982-1997. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 2001 Jun; 91(6):622-35.
• Nankivell P, Williams H, Webster K, Pearson D, High A, MacLennan K, Senguven
B, McConkey C, Rabbitts P, Mehanna H. Investigation of p16(INK4a) as a
prognostic biomarker in oral epithelial dysplasia. J Oral Pathol Med. 2014 Apr;
43(4):245-9
• Rettig EM, D’Souza G. Surg Oncol Clin N Am (2015)
• Termine N, Panzarella V, Falaschini S, Russo A, Matranga D, Lo Muzio L, Campi.
HPV in oral squamous cell carcinoma vs head and neck squamous cell carcinoma
biopsies: a meta-analysis (1988-2007). Ann Oncol. 2008 Oct; 19(10):1681-90.
• Uddin MN, Kouzi SA and Hussain MD. Strategies for Developing Oral Vaccines for
Human Papillomavirus (HPV) Induced Cancer using Nanoparticle mediated
Delivery System. J Pharm Sci. 2015; 18(2) 220 – 234.
More references available on request
Page 16
Post-Test
Instructions
•
•
•
Answer each question ONLINE (link provided on SMS website)
Answer post-course survey questions and click “Finish”
Deadline is March 31, 2017 (4:00pm EST)
1
T
F
In developed countries, the incidence of oral
squamous cell carcinoma (OSCC) is more than
oropharyngeal carcinoma (OPSCC).
2
T
F
Oropharyngeal squamous cell carcinoma (OPSCC) is
commonly seen in males.
3
T
F
The Human papilloma virus is usually cleared within
1-2 years in a patient with a good immune status.
4
T
F
The prognosis for HPV-positive cancer is worse than
HPV-negative cancer.
5
T
F
Ulceration and pain on the anterior tongue is the
most common presenting sign/symptom in
patients with oropharyngeal squamous cell
carcinoma (OPSCC).
6
T
F
HPV 16 and 18 are the strains associated in
development of oropharyngeal squamous cell
carcinoma (OPSCC).
7
8
T
T
F
F
A patient presenting with swollen lymph nodes on
his neck in the absence of any signs of disease in
the oral and oropharyngeal region, node
metastasis from Carcinoma of Unknown Primary
(CUP) may be considered in the differential
diagnosis.
HPV vaccines are 100% effective in preventing
oropharyngeal cancers (OPSCC).
Director
John R. Kalmar, DMD, PhD
[email protected]
Program Manager
Sydney Fisher, BS
[email protected]
Program Assistant
Nick Kotlar, BS
[email protected]