1. Influence of Risk Factors on HPV, Pap smear Abnormalities and/or Cervical Intraepithelial
Neoplasia
Shannon Laratonda
St. Francis University
November 30, 2010

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Abstract
The purpose of this literature review is to identify risk factors that have a positive
correlation with contracting human papillomavirus. Monitoring of the HPV infection is needed
to demonstrate protection against cervical cancer. Four articles have been analyzed using
populations of Tuscan, Danish, Greek, Estonian adult women. The two risk factors found to have
the strongest relationship with contracting HPV are young age and number of sex partners. Other
risk factors have also been found: ever having sex, alcohol consumption, low income, smoking,
marital status, number of full-term pregnancies, and number of partner’s partners also serve as
positive variables in detecting HPV infection.

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Introduction
Human Papillomavirus (HPV) is a viral infection spread through skin to skin sexual
contact. HPV is a group of over 100 different viruses, with at least 30 strains known to cause
different types of cancer, especially cervical cancer (CDC, 2010). As mentioned, HPV is
transmitted by skin to skin contact through vaginal, anal and oral sex with a partner who already
has HPV. If infected, signs and symptoms may take weeks, months and even years to appear. For
some individuals, symptoms may never appear and they may never know they have the infection
unless they were tested for it.
HPV is thought to be the most common sexually transmitted infection in the world. In the
United States, an estimated 75% to 80% of males and females will be infected with HPV in their
lifetime (Merck, 2009). For most, the virus will clear on its own, but when it doesn’t, HPV can
have consequences. Cervical cancer is the most common cancer in women worldwide. Risk
factors are variables associated with an increased chance of contracting a disease or infection.
Having a risk factor does not imply causal of infection but does have a positive relationship with
it. Researchers strive to find the responsible risk factors associated with HPV. This will enable
healthcare systems to help educate patients on preventative measures of contracting HPV and
thus, risk of cervical cancer. Identifying HPV risk factors will also allow laboratories to develop
the most useful treatments and/or vaccines. This review focuses on identifying risk factors that
have a positive correlation with HPV.
Method
This review analyzes four research articles identifying different risk factors that have a
positive correlation with HPV infection. Populations within the studies include adult women.
Criterion was entered in the PUBMED database to search for relevant articles. Research articles

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were found using keywords: Human papillomavirus, risk factors, HPV prevalence, and type-
specific incidence. Only articles published within the last five years were used. After analyzing
approximately a dozen articles, four which satisfy the specific criteria, were chosen for this
review. Each of the studies were carried out with female human adult populations and were
approved by review boards. Each article used study populations large enough to demonstrate
statistical significance if the study hypothesis is found to be true.
Literature Review
The purpose of this review is to identify risk factors that have a positive correlation with
contracting HPV. HPV is a common sexually transmitted disease that may lead to cervical
cancer. In a study conducted by Uuskula, Kals, Kosenkranius, McNutt, & DeHovitz (2010) type-
specific prevalence of HPV was assessed with different age groups in a population of Estonian
adult women. This study randomly selected women non-vaccinated for HPV ages 18-35 years by
mailing materials to 22,904 women from the Estonian Population Registry. Mailed to them, was
a specimen collection kit with instructions of how to self-swab a vaginal specimen, an informed
consent packet, and a 35-item questionnaire. Self-collected specimens were to be placed in a re-
sealable plastic bag (provided) with the signed consent form and questionnaire, and mailed back
to the laboratory.
Once the specimens were received in the laboratory, the DNA was extracted via
centrifugation and PCR (Uuskula et al., 2010). 326 specimens were received in the laboratory
and it was found that 38% (124 women) of the women tested positive for HPV (all types). The
age group of 21-25 years had the highest overall prevalence while the youngest, 18-20 years, had
the highest high-risk type prevalence. The overall prevalence of high-risk type HPV was 21%
and the overall prevalence of low-risk type HPV was 10%. The relative risk (RR) of 21% was

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calculated and the confidence interval (CI) shows that they are 95% sure that this value is
between 16-26%. The RR of 10% was also calculated and a 95% CI shows that this value is sure
to be between 7-14%. This data shows that of the 326 Estonian women participants,
approximately 68 of them have high-risk type HPV and approximately 33 of them have low-risk
type HPV. These percentages are noteworthy for a population of only 326 women. Applying
these findings to a larger population size of 1,000 (Estonian) women, 210 would be expected to
have high-risk type and 100 would be expected to have low-risk type HPV. In order for health
intervention programs and healthcare professionals to do their best to help decrease this
prevalence, risk factors must be indentified. Results the study’s questionnaire showed that
detection of HPV DNA had a positive correlation with age and sexual behavior risk factors;
specifically ever having sex, young age at debut, and higher number of sexual partners within the
last 12 months.
A study done in 2007 by Confortini et al. similarly found a positive correlation between
Tuscan women with HPV and number of sex partners (in past 3 years) and lifetime number of
partner’s partners. These researchers conducted a 3-year study with 1,066 Tuscan women
participants between the ages of 18-24 to investigate the prevalence, acquisition, clearance and
persistence of HPV infections in young Tuscan women and the risk factors correlated with such
events (Confortini et al., 2010). Invitations were randomly sent to a large number of 8,000
women to participate in this study. The 1,066 women (mean age of 21.6 years) who participated
received a clinical HPV test and a face-to-face interview at baseline. They were to report back in
6 months if their test was positive for another HPV test and colposcopy and 12 months for a
negative test; for 3 years. 30% of the population tested positive for several types of HPV.

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Of the 1,066 women that participated, they were all sexually active, not pregnant, never had a
hysterectomy, not previously treated for CIN, no known metabolic disease, never vaccinated for
HPV, and no cases of HIV. Seven women were excluded because they did not meet eligibility
criteria. 35% tested positive for HPV and were asked to return in 6 months. The other 70% were
to return in 12 months. Positive correlations were found with number of sex partners (in past 3
years) and lifetime number of partner’s partners. Number of sex partners was also found to have
a positive correlation with HPV in the previous study by Uuskula et al. (2010). This study is on-
going and another 3-year follow-up may provide more information; the study began in 2007.
Stamataki et al. (2010) conducted a study that found a positive correlation between Greek
women with HPV and number of sex partners, alcohol consumption, young age, and lower
income. The purpose of this study was to examine the HPV prevalence and distribution in
cervical smears in a sample of participants attending a gynecological outpatient clinic and to
explore the determinants of the infection (Stamataki et al., 2010). The population sample
consisted of 225 Greek women ages 16-45 years, attending a gynecological outpatient clinic.
During their visit, basic demographic information, sociodemographic characteristics, medical
history, smoking status, alcohol consumption and sexual and reproductive behavior was obtained
along with an HPV test via Pap smear. Women considered “newly diagnosed” pertained to
individuals with a negative history for HPV infection or individuals never tested for HPV. Non-
smokers have never smoked or have given up smoking for atleast 3 consecutive years. Heavy
drinkers had more than 1 drink per day. Women with a monthly income less than $1,000 were
considered low income. If they attended college or a university, they were considered high
education level.

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22.7% of the population of 225 women were positive for HPV infection; 17.3% of which,
were newly diagnosed. 68.4% had high education level, 45.3% had high monthly income, 52.4%
were unmarried, and 67.1% had their first sexual intercourse before age 20. 76.4% reported a
single regular sexual partner during the last year, 55.5% reported more than three partners during
their lifetime, and 29.3% had more than five sexual intercourses on a monthly basis. Condoms
were the most common contraceptives used (58.6%).
The findings from this study show that HPV has the strongest, positive correlation with
alcohol consumption and number of sex partners. Other risk factors found to have a positive
correlation are young age, lower income, marital status, number of full term pregnancies, and
smoking. These risk factors correlate with the previous two studies’ findings. All three studies
have found a positive correlation with number of sex partners and two of the three found young
age to be a risk factor also.
In a study conducted by Nielsen, Iftner, Munk, and Kjaer (2009), the incidence of type-
specific HPV was assessed and risk factors were examined for acquisition of high-risk HPV
infection in Danish, adult women. This study randomly selected 17,949 women ages 20-29 years
from a computerized registry of Copenhagen. After contacting the population, 11,088 women
were enrolled into the study. The women were asked to come to the laboratory for a face-to-face
interview and an initial gynecological examination with a repeat exam two years after. The face-
to-face interview consisted of questions about their sociodemographic variables, contraceptive
use, sexual habits, reproductive history and smoking habits. The gynecological examination
consisted of a pap smear, blood draw, and a biopsy for HPV testing. Of the women who made
the first laboratory visit, 8,656 women made the second visit two years later. The same steps
were taken at the second visit but the questionnaire was more focused on the past two years of

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their life (the time between the two visits). All participants gave informed consent beforehand
and this study has been approved by the Scientific Ethical Committee of Copenhagen and
Frederiksberg Municipality, Denmark (Nielsen, Iftner, Munk, & Kjaer, 2009).
The specimens taken during the examinations were tested for HPV via Hybrid Capture 2
(HC2) and LiPA V2 polymerase chain reaction (PCR) assay (Nielsen et al., 2009). Like in the
first mentioned study by Uuskula et al. (2010), PCR is a valid a reliable test for detecting HPV.
Genotyping was done so the specimen could be tested for several types of HPV. Women who
had one of the two specimens missing (from either the first or second visit) were excluded from
the study. This left a total of 7,454 participants for analysis which is a large population size to
demonstrate statistical significance if the study hypothesis is found to be true.
Of the 7,454 women, 16.2% of them (1,208 women) tested positive for high-risk (HR)
HPV at the first examination and 16.7% tested positive for HR HPV at the second examination
(Nielsen et al., 2009). 20.8% of women who initially tested positive for HR HPV at the first
examination, acquired new HR HPV types by the follow-up second examination. The RR was
calculated for 20.8% and a CI shows that they are 95% sure that this 20.8% value is between
18.5% and 23.1%. A total of 6.0% (448 women) tested positive for HR HPV at both
examinations and 73.1% women tested negative for HR HPV at both examinations.
The age-specific incidence was significantly higher in women aged 20-23 years than the
women aged 24-26 and 27-29 (Nielsen et al., 2009). A decreasing trend in incidence was
observed with increasing age. In the 20-23 age group of 1,959 women, 17.9% (95% CI 16.2-
19.6%) tested HR HPV positive which is higher than 12.3% (95% CI 10.9-13.7%) of the 2,032
women in the 24-26 age group and the 8.7% (95% CI 7.6-9.9%) of the 2,255 in the 27-29 age
group. These figures were obtained using age-adjusted regression models (SAS STAT version

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viewer 8.2). It was also found that no two specific HPV types are more likely to be acquired
together than any other pairing of HPV types. This was estimated by distinguishing between
acquisition by women who were HPV16-positive initially and those who were initially positive
for HPV types other than HPV-16.
Nielsen et al. (2009) found the most common types of HPV to be HPV52, HPV16, and
HPV31. Their article states that these results have been found in other studies as well. They
concluded that acquisition of multiple HPV types is common. Having multiple types of HPV is
recognized as a possible risk factor for HPV persistence which could lead to cervical cancer.
Whether cervical precancerous lesions result from certain types of HPV or the acquisition of
multiple types is unknown. Several studies have shown that women and men who are HR HPV
positive are very likely to acquire other types and that most HPV types are detected in
combination with other types.
Supporting the 3 previous studies, age and number of sexual partners were found to be
the two most important risk determinants when analyzing women positive with single or double
HR HPV types. This study also found oral contraceptive use to be the third most important risk
determinant.
Conclusions
Uuskula et al. (2010) found HPV to have a positive correlation with young age at debut,
ever having sex, and higher number of sexual partners within the last 12 months. These results
are supported by findings in a 2007 study conducted by Confortini et al. These researchers found
a positive correlation between Tuscan women with HPV and number of sex partners (in past 3
years) and lifetime number of partner’s partners. Stamataki et al. (2010) also found a positive
correlation between Greek women with HPV and number of sex partners, alcohol consumption,

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young age, and lower income. Number of sex partners and young age were found in two of the
first three articles. The study by Stmataki et al (2010) has limitations with population size (225
women). Also, a single negative HPV test result (carried out in their study) could lead to a
missed HPV infection; since 12 of their subjects previously tested positive for HPV but tested
negative in their clinic. In the fourth article by Nielsen et al. (2009) age, number of sex partners,
and oral contraceptive use were found to be the most important risk determinants when analyzing
women positive with single or double high-risk HPV types
The result that higher HPV prevalence has a positive correlation with being younger in
age, suggests that younger age groups are more likely to contract HPV than older populations.
Promiscuous populations who have a higher number of sex partners are also more likely to
contract HPV than populations with just one sex partner. We have seen that there are other risk
factors also associated with HPV contraction. Other findings included ever having sex, alcohol
consumption, low income, smoking, marital status, number of full-time pregnancies, and number
of partner’s partners. Once more research is conducted on these other mentioned risk factors, it
will be known how strong the relationships are between them and HPV and whether the
correlation is significant.
Nielsen et al. (2009) found the most common types of HPV to be HPV52, HPV16, and
HPV31. They also found that acquisition of multiple HPV types is common. Having multiple
types of HPV is recognized as a possible risk factor for HPV persistence which could lead to
cervical cancer. Whether cervical precancerous lesions result from certain types of HPV or the
acquisition of multiple types is unknown. A useful follow-up study could be conducted on this
correlation so maybe a type specific vaccine could be developed. A population of women could
be divided into a group having several types of HPV and 3 groups of single types. Several

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studies have shown that women and men who are HR HPV positive are very likely to acquire
other types. These findings may indicate that acquisition of one HPV type facilitates acquisition
of other HPV types, or that some women are more susceptible to HPV acquisition.
Discussion
One may conclude that the two most important determinants of HPV are young age and
number of sex partners. It has also been found that ever having sex, alcohol consumption, low
income, smoking, marital status, number of full-time pregnancies, and number of partner’s
partners also serve as positive variables in contracting HPV. Understanding these risk factors and
being able to educate others of them, is an excellent way of taking preventative measures for
HPV. Behaviors and habits are hard to change. When a patient comes into a doctor’s office, the
most they can do is try and convince a patient to change the behavior that is making them ill.
When the patient leaves though, it is up to them to actually change their way of living. If a
patient comes into a gynecologist’s office and tests positive for HPV, the most the doctor can do
is to educate the individual of the risk factors associated with the infection. It is up to the patient
to identify the risk factors associated with his/her life and change the way they are behaving in
that way. The doctor cannot change the behavior for them or make them stop their habits.
As a student striving to be a healthcare professional, one can better themselves by
identifying challenges like this and making an effort to overcome them. Excellent doctor’s will
sound extremely convincing and motivate their patients to change their behavior. A doctor may
refer them to counseling and be sure to educate the patient the best they can on a topic. For
doctor’s who specialize, they should really strive to know the in’s and out’s of the material in
their field. Research and textbooks should be a part of their everyday life. What one would
consider a “good” doctor may be one who is comfortable with calling on another doctor for

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advice to better themselves of a misunderstanding or a gray area. Life-long learners are the most
effective teachers and educators out there.

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References
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Human papillomavirus infection and risk factors in a cohort of Tuscan woman aged 18-
24. BMC Infectious Diseases, 10(157), 1471-2334.
Division of STD Prevention. (2010, October 13). Centers for Disease Control and Prevention.
Retrieved from http://www.cdc.gov/std/hpv/
Merck, S. (2009, November 3). Gardasil. Retrieved November 28, 2010, from
http://www.HPVinfo.com
Nielsen, A., Iftner, T., Munk, C., & Kjaer, K. (2009). Acquisition of high-risk papillomavirus
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type-specific prevalence of high-risk human papillomavirus infection in Estonia. BMC
Infectious Diseases, 10(63), 1471-2334.