Download than HPV 16 can be considered a risk factor for oral cancer, this is

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The Effect Human Papilloma Virus 16 has on Oral Cancer Prevalence: A Systematic Review
by
Rebecca McGruder
BS, Marquette University, 2003
Thesis Submitted in Partial Fulfillment
of the Requirements for the
Master's Degree in Public Health
Concordia University
May 2016
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Abstract
Oral cancer rates have been shifting in demographics and the Human Papilloma Virus 16 (HPV 16) has
been identified as a risk factor for many cancers. If a correlation with oral cancer can be shown; than
HPV 16 can be considered a risk factor for oral cancer, this is the purpose of this systematic review. It is
important to clearly understand this shift in order to properly prevent an increase in oral cancer rates.
The Health Belief Model suggests that behavior change will happen if the benefits outweigh the costs.
If a link to oral cancers through HPV 16 can be shown, then it will be an added motivator for HPV
prevention initiatives. This systematic review compared studies that investigated the prevalence of HPV
16 in oral carcinogenic tissue, through tissue sampling. These studies showed a correlation between
HPV 16 and oral cancer. A high rate of HPV 16 in carcinogenic tissue compared to healthy tissue
showed that HPV 16 has an effect on increased oral cancer rates. Treatments and prevention efforts can
be created utilizing this information.
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Introduction
Oral cancer rates have historically stayed consistent, but recently it has started to appear more
frequently in those under the age of 40. This increase in oral cancer rates has been theoretically
attributed to HPV 16 (Oral Cancer Foundation (OCF), 2015). It is important to understand this
increased cancer rate, in order to help prevent and understand the true effect HPV 16 has on oral cancer
incidences. The more information that can be gathered about this issue, the better information public
health professionals can supply to patients. A systematic review of the effect HPV 16 has on oral cancer
will help to improve education and provide motivation for protection against this virus.
Problem Statement
Oral cancer is a serious disease. In 2016, approximately 48,250 people will be diagnosed with
oral cancer (OCF, 2015). Oral cancer includes mouth, tongue, tonsil, throat, and oropharynx cancers. In
the past decade there has been an increase in the rate of oral cancers (OCF, 2015). While it may seem
like this cancer is rare, new oral cancer diagnoses happen 132 times a day, and one person dies from oral
cancer every hour. If found in late stages the death rate is 50% at five years from diagnosis (OCF,
2016). This shows that oral cancer is a prevalent cancer. Traditionally, tobacco and alcohol use have
been considered the main risk factors for oral cancer, but as prevalence of these risk factors decreased,
oral cancer rates have been increasing (Elango, Suresh, Erode, Subhadradevi, Ravindran, Iyer, Iyer, and
Kuriakose, 2011). Research has suggested that the Human Papilloma Virus (HPV), specifically high
risk strains like 16 and 18, can be an independent risk factor for cancers.
HPV is the most common sexually transmitted infection in the United States. HPV is so common
nearly all sexually active men and women get it at some point in their lives (Centers for Disease Control
(CDC), 2015). There are approximately 20 million active cases and 6.2 million new cases each year
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(Ault, 2006). Approximately 80% of women will have been infected with HPV by the age of 50
(Braaten and Laufer, 2008). HPV is a common infection with serious consequences. This makes
understanding its role in oral cancers an important issue.
Purpose Statement
The purpose of this research proposal is to synthesize the results of various research studies to
investigate the casual relationship between HPV 16, a specific strand of the virus, and oral cancer. If the
role of HPV 16 can be proven than research and interventions can be developed based on this
information. There have been many studies looking for the prevalence of the HPV 16 virus in
carcinogenic tissues. A systematic review of the gathered data will establish consensus of different
studies and the combined data will help to analyze the results.
Research Questions and Associated Hypotheses
The research question that relates to this review is: Is there a correlation between HPV 16 and
oral cancer? The null hypothesis is that if HPV 16 does not have an effect on oral cancer it will not be
found at a higher rate in carcinogenic tissue than normal tissue. The alternative hypothesis is that if
HPV 16 does have an effect on oral cancer the virus will be found at a higher concentration in
carcinogenic tissue than healthy tissue. A systematic review and meta-analysis will contribute to the
body of knowledge on this topic. Data will be gathered on HPV 16 and oral cancer in order to
understand the true relationship between them. A review of studies and data will show or not show a
correlation between disease and this virus. If a correlation is shown, education and programs can be
created with this knowledge, as well as contributing to the development of treatments and prevention
initiatives.
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Potential Significance
If a correlation can be proven treatments and prevention efforts can be created utilizing this
information. The goal of investigating the role the HPV 16 virus has on any cancer is to give credence
to the need to prevent infection of this virus. This virus is so common that nearly all sexually active
men and women get it at some point in their lives (CDC, 2015). If the casual relationship between oral
cancer and the HPV 16 virus can be proven it will not only help to develop treatments designed
specifically for this type of cancer, it will help to provide support and motivation for parents to vaccinate
their children against this virus.
HPV 16 is an independent risk factor for cancers and treatments can be designed with that
specific risk factor in mind. Identifying HPV 16 related tumors can be clinically significant, with
specific treatments that might improve the patient’s quality of life (Bixofis, Sassi, Patussi, Jung, Ioshii,
and Schussel, 2014). HPV cancers have a distinct molecular pattern and an improved response to
treatment and prognosis (Gan, Zhang, Gui, and Fan, 2014). This specific pattern shows a better
response to chemotherapy and radiation, with increased survival rates (Elango, et al, 2011). HPV 16
related tumors respond more successfully than tumors caused by different risk factors. If a correlation
can be shown than it will become more common place to check for the HPV virus and design treatment
with the virus in mind.
Vaccines have been developed for HPV 16 to prevent infection. Vaccination against this virus is
now recommended for young females in order to prevent cervical cancers (Lundberg, Leivo, Saarilahti,
Makitie and Mattila, 2011). Two prophylactic vaccines have been created and they have shown to be
highly effective in infection prevention and HPV related diseases (Ribeiro, Levi, Pawlita, Koifman,
Matos, Eluf-Neto, Wunsch-Filho, Curado, Shangina, Zaridze, Szeszenia-Dabrowska, Lissowska, Daudt,
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Menezes, Bencko, Mates, Fernandez, Fabianova, Gheit, Tommasino, Boffetta, Brennan, and Waterboer,
2011). If HPV 16 can be associated with oral cancers than this vaccination might be considered to be
preventive for oral cancers. If the vaccination is considered preventative for multiple cancers, then there
will be more compliance by parents to get their children vaccinated.
Background Literature Review
Search Strategy
The search engines used in the systematic review were Academic Search Premier, CINAHL Plus
w/Full Text, and PubMed. Keywords used were HPV 16 OR HPV AND Oral Cancer on articles
published between 2000-2016. The selection criteria were research articles on oral cancer that
investigated the relationship with HPV 16. Other inclusion criteria were primary research studies and
quantitative studies. The exclusion criteria were oral cancer not being the only cancer studied,
qualitative research articles, and Non-English articles.
Theoretical Foundation
The Health Belief Model was initially created 50 years ago to identify determinants of being
screened for tuberculosis and has been a part of public health ever since its creation (DiClemente,
Salazar, and Crosby, 2013). The Health Belief Model is a value-expectancy model based on the
principal that behavior change will only happen if the benefits outweigh the cost of the change. The
beliefs of an individual are an important construct. Perceived susceptibility and perceived severity are
important elements to motivate an individual to action (Riverside Community Health Foundation, n.d.).
An individual has a need to feel like they are susceptible to the condition and that the condition has
serious consequences. The benefits also need to outweigh the perceived barriers (DiClemente, Salazar,
and Crosby, 2013). A positive expectation will increase the motivation to change behavior. In order to
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achieve this, it is important to have a defined population at risk, clear consequences of the risk, specific
action to take, inclusion of barriers, and guidance to perform the action (Di Clemente, Salazar, and
Crosby, 2013). The Health Belief Model is beneficial for preventative health behaviors.
The Health Belief Model is helpful when motivating risk behavior like vaccinations. Studies
have shown that perceived risk and severity are important to vaccination behavior (Brewer, Chapman,
Gibbons, Gerrard, McCaul, and Weinstein, 2007). Meta-analysis shows that risk perceptions are
predictors of vaccination behaviors (Brewer et al, 2007). Research has shown that three factors explain
behavior in regards to vaccination; (a) perceived barriers to vaccination, (b) perceived benefits, and (c)
perceived severity of contracting the disease (DiClemente, Salazar, and Crosby, 2013). These factors all
correspond to concepts of the Health Belief Model. The Health Belief Model addresses all the barriers to
vaccination, and if the model is followed their can be successful behavior change. This demonstrates a
need to create better health promotion with improved information to increase vaccination compliance
(Donadiki, Garcia, Barrera, Sourtzi, Garrido, Andres, Trujillo, and Velonakis, 2014).
According to the Health Belief Model if perceived susceptibility and perceived severity of HPV
infection can be established than there will be an increased acceptance of a HPV vaccination. The
systematic review would support the perceived susceptibility and perceived severity, by improving the
information used to create health promotion. The research question of how HPV 16 relates to oral
cancer will provide information to prove severity of this virus. HPV is so common, it is estimated that
the majority of sexually active people will get the virus in their lifetime (CDC, 2015). If a correlation
between HPV 16 and oral cancer can be shown, that information combined with the susceptibility of
getting HPV will motivate increased vaccination, promoting healthy behaviors.
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Literature Review
Oral cancer rates are rising. In 2013 it is estimated that there will be an increase of 36,000 new
cases of oral cancer and 6,850 deaths attributed to oral cancer in America alone (Gan et al, 2014).
Traditionally, tobacco and alcohol use have been considered the major risk factors for oral cancer
(Lundberg et al, 2011). An increasing number of oral cancer patients have none of these traditional risk
factors (Elango et al, 2011). In recent years HPV has been identified as an independent risk factor for
many cancers, including oral cancer (Gan, et al, 2014). If HPV is considered an independent risk factor
for cancer than the relationship between oral cancer and HPV needs to be studied.
There is a possibility of a correlation between oral cancer and HPV 16. Over the last three
decades there has been an accumulation of data that supports the belief that HPV may be a causative
agent in oral cancers, specifically high risk strains like 16 (Elango et al, 2011). HPV has been
recognized as an independent risk factor for HPV (Gavid, Pillet, Pozzetto, Oriol, Dumollard,
Timoshenko, Martin, and Prades, 2013). HPV 16 has been found in cancerous tissues (Far, Aghakhani,
Hamkar, Ramezani, Pishbigar, Mirmomen, Roshan, Vahidi, Shahnazi, and Deljoodokht, 2007). This
evidence suggests that HPV 16 may be the cause for increased oral cancer cases. If the role of HPV 16
in oral cancer is proven than research and interventions can be developed based on this information.
HPV 16 and its relation to oral cancer has been studied using a variety of methods; case-control,
cohort, and biopsy. There have been many case-control studies and in these studies carcinogenic tissues
in the oral cavity and control tissues have been collected and tested for the presence of HPV 16 (Bixofis,
2014; D’Souza, 2007, Elango, 2011; Gan, 2014; Hansson, 2005; Ribeiro, 2011). Another method is
biopsy of known carcinogenic tissues in the oral cavity to look for HPV 16 virus (Far, 2007, Gavid,
2013; Khanna, 2009; Lundberg, 2011). Figuring out if the virus is in carcinogenic tissue or not is
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important to establishing if there is a casual relationship between the virus and cancer. A systematic
review of the gathered data will establish the consensus of these different research articles. It is
important to combine the data in order to synthesize the results.
Methodology
A systematic review was used to combine the findings of research studies that investigated the
relationship between oral cancer and HPV 16. In this review the research question was based on
whether there is or is not a correlation between oral cancer rates and HPV 16. A systematic review is
the best design to study large amounts of data. It allows for a combining of data from multiple studies
and synthesizing of the results. This design was chosen to understand the extent HPV 16 has on oral
cancer rates in order to assess the need for prevention and education based on the studied risk.
Inclusion and exclusion criteria
Computer based searches to locate relevant articles were utilized from Academic Search
Premier, CINAHL Plus w/Full Text, and PubMed. The keywords used were HPV 16 OR HPV AND
Oral Cancer. Articles were searched and chosen that studied the correlation between HPV 16 and oral
cancer. Primary research articles and quantitative studies were included, as well as publications from
other countries, studies only reported in English, studies conducted from 2000-2016, and studies that
used similar measuring tools. After the exclusion of articles that did not fit these criteria, the remaining
articles were compiled and a manual search was done. The inclusion and exclusion criteria used to
evaluate these articles manually are listed in Table 1.
Table 1
Inclusion and Exclusion Criteria
Inclusion Criteria
Primary Research Article
Exclusion Criteria
Non Full Text
10
Quantitative Studies
Oral cancer is being studied
HPV 16 is the virus being studied
Correlation of HPV 16 and Oral Cancer
Non Scholarly articles
Publications not between 2000-2016
Risk Factor is not HPV 16
Oral Cancer is not the only cancer studied
Qualitative research articles
Data analysis plan
Once the inclusion and exclusion criteria were identified, it was determined that 10 articles from peer
review journals would be included. The number of findings and rationale were presented in Figure 1.
Records identified through
database searching (n = 3,248)
Additional records identified
through other sources (n = 0)
Records screened by titles and abstracts
(n = 3,248)
Records screened
(n = 3,248)




Studies included in
systematic review (n = 10)
Figure 1: Results of inclusion and exclusion criteria.

Records excluded
(n = 3,238)
Non full text (n=443)
Non English (n=27)
Publication not
between 2000 and
2016 (n=214)
Oral cancer not the
only cancer studied
(n=2,530)
Qualitative studies
(n=24)
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Results
Data Collection
Word and Excel software was used to analyze the data in this systematic review. The results
from the individual studies, the methods, and the prevalence of HPV 16 were compared. The main
outcome of interest is the prevalence of HPV 16 in oral carcinogenic tissues. If there is a high
prevalence of HPV 16 in carcinogenic tissues versus healthy tissues than a correlation can be shown and
the hypothesis is true. The characteristics of the included studies, discussing the setting, design,
intervention, and outcomes are included in Table 2. The quality score is also represented, which was
created through methodology scoring.
Table 2
Characteristics of Included Studies (Quantitative)
Study
(Authors
name)
Setting
Study
Design
n
Population
Intervention
Primary
Outcomes
Quality
Score
Gan et al
2014
Hospital
Case
Control
200cases
Casesconfirmed
diagnosis of
OSCC with no
other tumors
Polymerase chain
reaction and DNA direct
sequencing were used to
identify HPV types in
tumors
Cases with
HPV 16 types
4
Polymerase chain
reaction and p16 protein
expression by
Immunohistochemistry
was preformed to
determine presence of
HPV
Cases/Controls
6
with presence of
HPV 16
68controls
Controlspatients with
no history of
cancer
Elango et
al, 2011
Cancer
Centre
Case
Control
60-cases
46controls
Cases- tissue
samples from
diagnosed
tongue cancer
Controlmatched to
cases, but with
no cancer
12
Bixofis et
al, 2014
Hospital
Cohort
78
Patients with
SCCO as
primary tumor
that have not
had
antineoplastic
treatment
P16 protein expression
by
Immunohistochemistry
Cases that
stained positive
for p16
4
Ribeiro et
al, 2011
Hospital
Case
Control
2214cases
Cases-Patients
with oral
cancer
Serum samples were
taken to test for HPV
antibodies
Cases and
Controls that
tested positive
for HPV 16
antibodies
5
Serum samples were
taken to look for HPV
DNA
Cases and
Controls that
tested
Seropositive for
HPV 16
5
3319controls
D’Souza
et al, 2007
Hospital
Case
Control
100cases
200controls
ControlsPatients from
same area with
no cancer
CasesPatients with
newly
diagnosed
oropharyngeal
cancer
Controlspatients
without cancer
Lundberg
et al, 2011
Hospital
Cohort
135
Patients
treated for
HNSCC with
adequate
paraffinembedded
tumor biopsies
P16 protein expression
by
Immunohistochemistry
Samples that
tested positive
for p16
5
Gavid et
al, 2013
Hospital
Case
Study
200
Patients with
newly
diagnosed
HNSCC with
no prior
history of head
DNA detection of HPV
and p16
Immunohistochemical
staining
Samples that
tested positive
for p16
3
13
and neck
cancer
Far et al,
2007
Hospital
Case
Study
140
Patients with
dysphagia
were tested for
squamous cell
carcinoma
HPV DNA was analyzed
through polymerase
chain reaction
Samples that
tested positive
for HPV
2
Khanna et
al, 2009
Hospital
Case
Control
Study
75- cases
Case-Oral
cancer and
Leukoplakia
patients
Southern blot
hybridization technique
was used to detect the
presence of HPV 16
Samples that
tested positive
for HPV 16
4
Polymerase chain
reaction and DNA
sequencing was used to
establish HPV
prevalence
Cases that
tested positive
for HPV
5
45controls.
Controlnormal oral
mucosal
Hansson
et al, 2005
Hospital
Case
Control
131cases
320controls
Case- Patients
with OOSCC
and no
previous
cancer
diagnosis
ControlPatients with
no previous
cancer
diagnosis,
same age,
same sex,
same region as
cases
The primary outcomes all determined the existence of HPV 16 in carcinogenic tissues, using
various techniques. The main differences were the methods used to determine the prevalence of HPV
16. The main techniques used were Immunohistochemical staining to look for the p16 protein or DNA
sequencing to look for HPV 16 specifically. Both prove a prevalence of HPV 16 if found. They are all
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consistent with each other and share a common primary outcome. This primary outcome fits into the
systematic review question of the prevalence of HPV 16 in oral cancer. The quality score was low for
the Far et al (2007) study and that was due to low scores in study design and clarity, this eliminated this
study from the review. The studies with the highest score; Hansson et al (2005), Lundberg et al (2011),
D’Souza et al (2007), and Ribeiro et al (2011) all scored high on clarity and study design which makes
them more significant. Only one, Ribeiro et al (2011), did not show consistency with the research by
showing no significant correlation between HPV 16 and oral cancer. The major differences were the
amount of participants in the study. The changes in the included studies due to quality assessment
scores is reflected in Figure 2.
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Records identified through
database searching (n = 3,248)
Additional records identified
through other sources (n = 0)
Records screened by titles and abstracts
(n = 3,248)
Records screened
(n = 3,248)
Studies included in
systematic review (n = 10)





Records excluded
(n = 3,238)
Non full text (n=443)
Non English (n=27)
Publication not
between 2000 and
2016 (n=214)
Oral cancer not the
only cancer studied
(n=2,530)
Qualitative studies
(n=24)
9 studies with Methodology
score of 3 and higherincluded in analysis
Figure 2. Flowchart of the design of the systematic review
Results
The intervention and measures were analyzed to figure the results and find the significance in
each study. The significance was measured because it determines whether the alternative hypothesis or
the null hypothesis is true. The included studies were evaluated based on the intervention, measures,
results, and significance. These criteria showed whether the results were significant. The outcomes of
this evaluation is shown in Table 3.
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Table 3
Results of Included Studies
Author
Quality Intervention
Score
Gan et al
2014
4
DNA sampling
from tissue
Elango et
al, 2011
6
Tissue
sampling
Bixofis et
al, 2014
4
Immunohistochemically
staining
Oral cell
sampling
Ribeiro et 5
al, 2011
D’Souza
et al,
2007
5
Lundberg
et al,
2011
Gavid et
al, 2013
5
Khanna
et al,
2009
4
Hansson
et al,
2005
5
3
Measures
Results
Significance
Polymerase chain
reaction
DNA direct
sequencing
Polymerase chain
reaction
P16 protein
expression
P16 protein
expression
39 cases (19.5%) had
HPV 16 and 0 controls
had HPV 16
Yes, P-values
<0.05
HPV was detected in
29 (48%) of cases and
0 of the controls
Yes, P-values
<0.05
86.3% (67) of cases
stained positive for p16
Yes, P-values
<0.05
Serum sampling
5.7% of cases tested
positive for HPV
antibodies and 2.6% of
controls tested positive
for HPV antibodies
57 (57%) of cases
tested Seropositive and
14 (7%) controls tested
Seropositive
48 (36%) of biopsies
were positive for p16
Not Significant,
P-Values >0.05
23 (11%) of biopsies
were positive for HPV
Not Significant
in Oral cavity, PValues >0.05
41 (54.6%) of cases
tested positive for HPV
16 and 9 (20%) of
controls tested positive
for HPV 16
52 (40%) cases were
positive for HPV DNA
and 3 (0.94%) of
controls tested positive
Yes, P-values
<0.05
Oral-mucosal
specimens
through
cytology brush
Immunohistochemistry
Serum sampling
Biopsy
samples and
Immunohistochemistry
Biopsy
samples
DNA detection of
HPV
P16 protein
expression
Southern blot
hybridization
Biopsy
samples
Polymerase chain
reaction
DNA sequencing
P16 protein
expression
Yes, P-values
<0.05
Yes, P-values
<0.05
Yes, P-values
<0.05
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These outcomes showed general consistency between studies, with most studies showing
significance with p- Values less than 0.05. Ribeiro et al (2011) and Gavid et al (2013) were the only
studies with a non-significant p- Value. This is relevant because Ribeiro et al (2011) was the largest
case and control population study. Overall the consistency of the results showed that the alternative
hypothesis may be accurate and HPV has a relationship with oral cancer. In the majority of the studies
the cases had a higher percentage of HPV prevalence than the controls. Figure 3 shows the percentages
of positive HPV samples. The cases and the controls are compared and show that the cases have a
higher prevalence of HPV virus than the controls. The exception is Ribeiro et al (2011), which had only
a small difference between case and control percentages.
Figure 3. Prevalence of HPV comparison
Figure 4 below shows the difference between the studies that show there is no causal relationship
between HPV 16 and oral cancer and those that do show a correlation. On the left side are the studies
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that proved the null hypothesis and on the right side are the studies that proved the alternative
hypothesis.
Null Hypothesis Proven
Ribeiro et al (2011)
Gavid et al, 2013
Alternative Hypothesis
Proven
Gan et al 2014
Elango et al, 2011
Bixofis et al, 2014
D’Souza et al, 2007
Lundberg et al, 2011
Khanna et al, 2009
Hansson et al, 2005
Figure 4. Results of systematic analysis
Figures 3 and 4 show that there are similarities between the data within the studies and a metaanalysis is appropriate. The patients within each study are similar, patients with oral carcinogenic tissue
were compared against those with only healthy tissue. The studies all compared similar exposures and
reported similar outcomes. In order to check if the results are homogenous and the confidence intervals
are relative to each other a forest plot needed to be created. Figure 5 is the created forest plot showing
that it is appropriate to perform a meta-analysis.
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Study
Gan et al, 2014
Elango et al, 2011
Ribeiro et al, 2010
D' Souza et al, 2007
Lundberg et al, 2011
Hansson et al, 2005
Grand Total ES
-10
-5
0
5
10
15
20
Risk Ratio
Figure 5. Forest Plot
Figure 5 shows a forest plot that showcases that the study’s results are similar enough to perform
a systematic review. Ribeiro et al (2011) has a long length to its line, which means it has a higher gap
between confidence intervals. This shows a less effective treatment result. The forest plot also shows
small squares which represent the size of the study. These studies all have smaller size participants.
The forest plot shows that the estimates are not varied and the confidence intervals overlap. This means
the data can be analyzed together.
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Discussion
Oral cancer rates have been increasing, even though prevalence of the main risk factors, tobacco
and alcohol use, have decreased (Elango et al, 2011). This leads to the supposition that other risk factors
need to be identified in order to decrease prevalence. Research has suggested that HPV can be an
independent risk factor for cancers (OCF, 2015). High risk HPV, like HPV 16, causes cell changes and
are considered more likely to grow into cancer (American Cancer Society (ACS), 2015). The more
scientific evidence that can be found on the prevalence of HPV in carcinogenic tissue, the more it will
help to support HPV as a causative agent for cancer.
Analyzing studies that look at the prevalence of
HPV 16 in oral cancer will help to support this theory and prevention measures can be implemented
around this virus.
This systematic review was performed using nine studies that tested for the prevalence of HPV
16 in carcinogenic tissue, and those that compared the amount of virus in cancerous versus noncancerous tissue. All of these studies looked for the prevalence of HPV 16 in tissues. The objective was
to combine the data in order to see if there was a causal relationship between oral cancer tissue and HPV
16. The findings of this review suggest that there is a causal relationship between HPV 16 and oral
cancer.
The results suggest that there is a high rate of HPV 16 in carcinogenic oral tissue, and that when
compared to the rate in non-carcinogenic tissue there is a difference in virus counts. This suggests that
HPV 16 may have a causal relationship with oral cancer, making it a possible risk factor. It is supposed
by many cancer related professional organizations and researchers that HPV 16 can be a cause of oral
cancer (ACS, 2015, American Dental Association, 2012, CDC, 2016, and OCF, 2015). Seven of the
analyzed studies showed a high prevalence of HPV 16 in oral carcinogenic tissues (Gan et al, 2014,
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Elango et al, 2011, Bixofis et al, 2014, D’Souza et al, 2007, Lundberg et al, 2011, Khanna et al, 2009,
and Hansson et al, 2005). Two of the analyzed studies show no significant prevalence of HPV 16 in
tissues (Gavid et al, 2013, and Ribeiro et al, 2011). When the data is analyzed together it shows the
possibility of a relationship between HPV 16 and oral cancer. This adds to the body of knowledge of
studies showing a correlation between HPV and oral cancer, and helps to support the theory that HPV is
a human carcinogen. The similarities between the studies allows for a discussion of the possibility of
HPV as a causal agent in oral cancer. The studies all tested for the significance of the virus in oral
cancer tissues, the scope of the data was if there were or were not significant levels of virus in tissues.
All but two of the studies showed that there were significant levels of virus in oral cancer tissue. The
analyzed data shows a correlation between HPV 16 and oral cancer, which answers the review question.
The Health Belief Model is a value-expectancy model based on the principal that behavior
change will only happen if the benefits outweigh the cost of the change. The attitudes and beliefs of the
individual are the main motivators for change. An individual has a need to feel like they are susceptible
to the condition and that the condition is serious (DiClemente, Salazar, and Crosby, 2013). This study
shows a possible correlation between HPV and oral cancer. This information will help to influence
attitudes and beliefs of the individual toward vaccination. The results help to show that there is risk,
clear consequences of the risks, and a specific action that can be taken to prevent the risk. These results
show a connection between the virus and oral cancer, which supports the perceived susceptibility and
perceived severity of the virus. This will help change attitudes toward HPV vaccination using the
Health Belief Model.
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Limitation of the Study
There are limitations in this review in regards to the inclusion criteria. Non-English articles were
excluded due to the author’s inability to translate other languages. There was also no other individual to
cross check the studies or the data. Publication bias may also have been introduced because the author
did not search all registers for unpublished trials. This was due to lack of time and resources. The author
has an educational history with oral health and that may introduce a professional bias by preventing an
unbiased assessment of the research. The author addressed this potential bias by evaluating and
including every study that researched a relationship between HPV and oral cancer. The included studies
had to be testing for viral loads within carcinogenic tissue, and the results were not taken into
consideration until data extraction.
In the included studies viral loads were assessed in healthy and unhealthy individuals in various
demography, race, age, sex, and geography, yet there were still some weaknesses in the studies that
effect generalizability. All the primary outcomes were homogenous in the included studies. One study
was eliminated due to a low quality score, Far et al (2007), and that was due to bad study design and
lack of clarity within the study. Two of the included studies had different results than the others; Ribeiro
et al (2011) and Gavid et al (2013). These studies showed no significance in the viral load between
samples. Three studies could not be included in the forest plot; Bixofis et al (2014), Gavid et al (2013),
and Khanna et al (2009). This was due to lack of data and the authors lack of resources to generate the
missing data. Half of the included studies had sample sizes that were less than 100 participants and only
one study had over a 1,000 participants. This effects the generalizability of the study. More studies
should be done with larger pools of participants for real generalizability.
23
The majority of the included studies showed significance with a p-value of < 0.05, which shows
validity within the included studies and in the results of this systematic review. Even with these
limitations the results show a connection between HPV and oral cancer. These limitations reflect a need
for further research in order to show a strong causal relationship.
Recommendations
Future research should attempt to address the above mentioned limitations. Even with
limitations the research question was answered. All the studies showed a statistical significance when
evaluating the level of virus in oral cancer tissues, thus showing a correlation between HPV and
carcinogenic oral tissue. There are recommendations that would improve the quality of research and add
strength to the scientific argument that there is a casual relationship between this virus and oral cancer.
A more thorough analysis of studies in different languages might lead to the inclusion of more studies.
The addition of a statistical analysis by a mathematical professional might lead to more data extraction.
These recommendations would lead to a systematic review with less limitations.
Further research that should be done when conducting studies should include larger data pools.
The main limitation to the included studies was the size of participants within the research studies. This
systematic review shows a correlation between HPV 16 and oral cancer, building on these results shows
a need for more research with larger data pools for increased scientific credibility. The results of this
review show that larger studies would be valuable and are needed. These large participant based studies
would be a good use of resources.
Implementation for Social Change
This review provides further data showing the potential HPV has a human carcinogenic. This
information can be used by physicians and people of trust to further show evidence of the benefit to
24
vaccination against this virus. The correlation between HPV 16 and oral cancer is shown, which means
that this vaccine can be considered preventative against this form of cancer. Proving that HPV causes
multiple cancers would create a stronger motivation for parents to get their children vaccinated. This
information will also help to motivate policy changes supporting the HPV vaccination. The more
children vaccinated the better the health of the population as a whole.
The more information gathered that shows HPV as a human carcinogenic the more credence will
be given to prevent infection of this disease. Preventative initiatives should be created with this data.
Public health professionals should use this information to promote prevention of HPV infection.
Initiatives should be created endorsing the need for HPV vaccination. This study shows that prevention
of this virus may lead to decreased oral cancer rates. The more people vaccinated the less incidence of
oral cancer. Treatments should also be developed for oral cancer with this information. When treating
oral cancer, the virus should be looked for and a specific treatment plan should be designed with this
information.
Conclusion
Preventing HPV infections will increase the general health of the population. The more known
about risk factors for disease the better we are able to prevent disease. Understanding various human
carcinogenics will help to combat and prevent cancers, thus improving the health of the community. It is
essential to understand all the factors that cause disease within the population in order to increase the
education of the population. An educated population will be motivated to make better health decisions.
This information will help to change the attitudes and beliefs of parents towards this vaccination.
25
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