1

Is Oral Sex Really a Dangerous Carcinogen? Lets Take a

Closer Look jsm_2684 1..9

Sara E. Rosenquist, PhD, ABPP

Private Practice Chapel Hill, NC, USA

DOI: 10.1111/j.1743-6109.2012.02684.x

ABSTRACT

Introduction. Questions have recently arisen in the popular press about the association between specific sexual
behaviors, namely, fellatio and cunnilingus, with head and neck cancers. Although there has been an overall decline
in the incidence of head and neck cancers over the past 25 years, there has been a shift in the distribution of these
cancers toward a particular type known as oral squamous cell carcinomas (OSCCs), and a younger demographic.
These particular cancers, OSCCs, have been shown to be associated with the human papillomavirus (HPV). Several
researchers have suggested that this shift in the epidemiology of head and neck cancers might be attributable to
changing sexual practices. While this speculation has caught on in the popular press, there are several interesting
contradictions in the existing evidence that suggest this conclusion might be premature and overreached.
Aim. The intent of this article is to help clarify the issues so that sexual medicine professionals can give accurate and
up-to-date information to their patients.
Main Outcome Measures. This is a review article; no outcome data are reported. This is a review article; no
measures were collected.
Methods. Pubmed search on HPV, oral sex, oral cancers, and OSCCs.
Results. One hundred ninety-six articles on HPV were found; 63 articles on oral sex, 55 on oral cancer, and 5 articles
on OSCCs were identified as relevant.
Conclusions. HPV infections occur commonly and are usually cleared within 18 months, thus HPV infection should
not be a cause for concern among monogamous couples with a rich and varied sex life as long as the sexual system
remains closed and other immune compromising factors are not present. HPV becomes a concern in the context of
immune system compromise and infection persistence. Factors contributing to immune system compromise, HPV
persistence, and oncogenesis are reviewed. Rosenquist SE. Is oral sex really a dangerous carcinogen? Lets take
a closer look. J Sex Med **;**:****.
Key Word. HPV; Oral Sex; Oral Cancers; Fellatio; Cunnilingus; Sexually Transmitted Infections; STDs

Introduction have declined since 1975 [1]. Regrettably, research

in this area combines statistics on cancers from

T he popular press has recently raised ques-

tions about the association between specific
sexual behaviors, namely, orogenital and oroanal
contact, with head and neck cancers. This article
was written in hopes of articulating the issues
clearly so that nonmedical practitioners such as sex
therapists, educators, and counselors can give
accurate and up-to-date information to their
patients.
Cancers of the head and neck are very rare,
occurring in about 10 out of every 100,000, and
various specific sites in the head and neck, typically
classifying them as head and neck cancers and
sometimes as oropharengeal cancers. Most head
and neck cancers occur among people who are over
60 and are associated with lifelong smoking and
heavy alcohol use [2]. Researchers have attributed
this age-related decline in head and neck or
oropharengeal cancers to the decline in tobacco
and alcohol consumption in the United States since
1920 [2]. However, there is a recent trend that
has caught the attention of epidemiologists and

2012 International Society for Sexual Medicine J Sex Med **;**:****

2 Rosenquist
oncologists who study these cohorts. Specifically,
they noted a small but significant increase in head
and neck cancers among a younger group [2].
While there are many different kinds of head and
neck cancers, there has been a shift in the distribu-
tion of these cancers toward a particular type known
as oral squamous cell carcinomas (OSCCs). Refer-
ences to an epidemic of oral cancer stem from this
shift in the distribution of OSCCs and not to actual
increases in overall incidence rates of oral cancers.
OSCCs have been shown to be associated with
the human papillomavirus (HPV), specifically the
high-risk strains that have already been shown to
cause cervical cancer [3]. The anatomic sites most
strongly associated with HPV-related OSCCs are
the tonsil and base of the tongue [2]. Several
researchers have suggested that this shift in the
epidemiology of head and neck cancers might be
attributable to changing sexual practices [46].
While this speculation has caught the attention of
the popular press, there are several interesting
contradictions in the existing evidence that sug-
gest this conclusion might be premature and
overreaching.
HPV
HPVs are small circular double-stranded DNA
viruses, ultramicroscopic microparasitic organisms
that live within our cells. Seventy to a hundred
different HPV genotypes have been identified;
some are common and benign, but some cause
disease [3]. The strains of HPV that have been
linked to cancer are called high-risk types. About
15 different types of HPV are considered high
risk, and of the high-risk HPV strains, HPV 16 [1316]. While the above can characterize the cel-
and 18 are the most frequently implicated in cer-
vical cancer [7,8]. HPVs are strictly epitheliotro-
pic, meaning they exist only in tissues that form
the covering of internal and external surfaces of
the body, including the surfaces that line the
vessels and small cavities of the body. The different
strains of HPV preferentially infect different ana-
tomic sites, and researchers subdivide them into
categories accordingly: cutaneous and mucosal.
The mucosal types are predominantly found in the
anogenital tract and also in the aerodigestive tract
[3].
Some strains of HPV are widely believed to
cause cancer. Researchers have not determined the
exact mechanisms or action, but some processes
have been identified. The HPV genome may be
divided into a coding and a noncoding region. The
noncoding region is thought to comprise about
15% of the viral genome, which is the long control
J Sex Med **;**:****
region (LCR). The LCR contains the origin of
viral DNA replication and the enhancer/promoter
elements regulating the viral transcription. Scien-
tists believe that the coding region consists of open
reading frames and encodes the early (E) and
late (L) viral proteins. The E proteins are
involved in regulation of viral transcription and
DNA replication, while the late genes encode
structural proteins, the viral capsid proteins (L1
and L2). Capsid proteins self-assemble into the
viral capsid, which interacts with a receptor of the
target cell facilitating entry of the viral DNA.
Early proteins E1 and E2 both play a role in the
viral DNA replication. E2 is also important in
the viral transcription regulation. E4 may facilitate
viral particle release by collapsing the cytokeratin
skeleton, while E5 is expressed in productive infec-
tions. Yet, E5s contribution to naturally occurring
infections remains poorly understood. The onco-
genic proteins E6 and E7 of high-risk HPV types
interfere with the cell cycle control by reducing
the availability of the hosts oncosuppressor
protein p53 and retinoblastoma protein [3].
These processes can then result in uncontrolled
cell proliferation [3].
The mere presence of HPV does not determine
cancer risk even when several high-risk strains are
present in the same person. HPV becomes a risk
factor when it persists over time and the bodys
natural defenses are unable to clear it [912].
Other risk factors must be present in order for an
HPV infection to persist, and those other risk
factors include environmental, genetic, as well as
behavioral variables that are many and varied
lular level processes, the exact nature of how that
interacts with predetermining vulnerabilities with
subsequent cancer occurrence remains unknown.
Natural Course of HPV
HPVs occur so commonly that they have been
found in the mouths of between 4% and 87% of
newborn babies [17]. Most of the HPVs found in
infants were strains 16 and 51, and sometimes dif-
ferent from the strains of HPV found in the
parents [18]. In fact, the concordance of HPV
types in newborns and their mothers is only in the
range of 5769%, and is unrelated to mode of
delivery, whether vaginal or cesarean [17], leaving
researchers at a loss to explain exactly how HPV is
transmitted.
Findings suggest that HPVs, including the
high-risk strains associated with cancers, are
common in newborns and are also gradually
Caution in the Narrative about HPV and Oral Sex Is Indicated
acquired throughout childhood [1719]. Specifi-
cally, the prevalence of HPV is bimodally distrib-
uted among children: the highest prevalence rates
are among babies less than 1 year old and adoles-
cents 1320 years old [17,18]. However, no HPV
was found in children between the ages of 7 and 12
[20]. HPVs, including high-risk mucosal HPVs 16
and 18, have been found in tonsillar and adenoid
samples of healthy children with normal mucosa
and also in children with tonsillar hyperplasia,
chronic tonsillitis, or adenoid hyperplasia. Among
adolescents, there is no statistically significant
association between HPV in the oral cavity and
any of the factors commonly thought of as being
associated with higher risk including gender, edu-
cation, HPV-related conditions, smoking history,
number of sex partners, adolescents smoking
history, or history of sexual activity [17].
HPV infections are much more common than
HPV-associated disease, which suggests that many
factors contribute to the clearing or persistence
and progression of HPV infection [21]. Since
HPV is an exogenous infectious agent, the
immune system response (the mucosal immune
system is involved in the local defense at mucosal
sites) probably plays a pivotal role in the outcome
of any HPV infection, influencing whether the
virus will be cleared or go on to become persistent
[3]. Many unknowns remain, including the precise
mechanism by which HPV induces carcinogenesis
and whether perinatally acquired HPV infection
might actually induce immunological tolerance or
even be protective in some way [21].
Cervical cancer was the first cancer to be asso-
ciated with HPV, and HPV is now widely consid-
ered to be a necessary but not sufficient cause of
cervical cancer in women [22]. Nonetheless, only a
small percentage of HPV-infected women go on to
develop cervical cancer; the vast majority of
infected women clear their cervicovaginal infec-
tions spontaneously. Moreover, several studies
now show that cervicovaginal HPV is predomi-
nantly self-limiting with a median duration of
812 months [23]. The risk factors most consis-
tently associated with progression of high-risk
HPV to cervical cancer (in the largest epidemio-
logical studies using the most sensitive detection
methods) were as follows: high parity (number of
children), long-term oral contraceptive use,
smoking, and coinfection with other sexually
transmitted diseases [24].
HPV seems to be involved in dynamic patterns
of infection and clearing. Large longitudinal
studies show that HPV infections are not only
3
short lived but also episodic, coming and going,
clearing and reappearing, and waxing and waning
over time [25]. Furthermore, HPV infections
accumulate quickly in sexually active women under
the age of 20 and then clear in women over 25.
The prevalence of HPV infections continues to
decline until after menopause when it begins to
pick up again as more postmenopausal women fail
to clear their infections [26]. Women who have
precancerous or cancerous lesions of the cervix are
consistently found to have a higher viral load than
women who do not have cytological abnormalities.
However, it is becoming apparent that the rela-
tionship between viral load of cervical HPV infec-
tions and cervical neoplasia is quite complex [12].
Although HPV is widely considered to be a
sexually transmitted infection, large longitudinal
studies involving couples suggest that the mode of
transmission might be more ambiguous [27]. In a
prospective Finnish family HPV study, both hus-
bands and wives were tested at both oral and genital
sites on several occasions [28]. Results showed that
the oral and genital HPV types found in couples
differ so that the strains infecting one partner are
only modestly correlated with strains infecting the
other [28]. The prevalence of oral high-risk HPV
infections fluctuated between 15% and 27%. Oral
and genital HPV strains were not only poorly cor-
related within subjects but also highly discordant
within couples. Twelve percent of women and 26%
of men reported regular oral sex. However, oral sex
habits were not associated with oral or genital HPV
infection. Similarly, no association was established
between oral HPV infections in either spouse and
the outcome of the partners genital HPV infection
during follow-up nor did HPV infection detected
in the seminal fluid have any association with the
oral HPV status of the female partner [28]. Partners
cleared various HPV infections at different rates.
Men started clearing their HPV infections sooner
and completed clearance more quickly than did the
women. These researchers concluded that Oral
sex had no association to oral HPV infection, but a
persistent oral HPV infection of the spouse
increased the risk of persistent oral HPV infection
10-fold in the other spouse. [28] Persistence rather
than the mere presence of infection or the practice of
oral sex contributed to the correlation of HPV
within the couple. Thus, not only do HPV infec-
tions wax and wane within an individual body, they
also wax and wane within the dynamic system of a
couple but when infection becomes persistent in
one, it is also likely to become persistent in the
other.
J Sex Med **;**:****
4 Rosenquist
HPV and Cervical Cancer
According to the World Health Organization, cer-
vical cancer is second only to breast cancer as the
leading cancer among women [29]. In 1999,
researchers definitively concluded that HPV is a
necessary (though not sufficient) cause for cervical
cancer: the worldwide HPV prevalence in cervi-
cal carcinomas is 99.7 per cent. The presence of
HPV in virtually all cervical cancers implies the
highest worldwide attributable fraction so far
reported for a specific cause of any major human
cancer. The extreme rarity of HPV-negative
cancers reinforces the rationale for HPV testing in
addition to, or even instead of, cervical cytology in
routine cervical screening [22].
Cervical cancers are higher among women who
have other risk factors: Co-factors that modify
the risk among HPV DNA positive women
include the use of oral contraceptives (OC) for
five or more years, smoking, high parity (five or
more full term pregnancies) and previous exposure
to other sexually transmitted diseases such as
Chlamydia Trachomatis (CT) and Herpes Simplex
Virus type 2 (HSV-2) [30]. Interestingly, a
womans risk for cervical cancer is defined not
only by the number of her sexual partners but also
by the number of sexual partners her husband
or male partner may have had: the presence of
HPV DNA in the husbands penis conveyed a five-
fold increased risk of cervical cancer to their wives.
The odds of cervical cancer among monogamous
women increased up to 9- to 10-fold in relation to
the presence of high-risk HPV types in the penis
of their husbands [31].
HPV and Head and Neck Cancers: Myth vs. Reality
Coinciding with the release of vaccines to protect
against HPV, there has been a proliferation of
interest in the popular press about the risks of
other HPV-related cancers. Some articles claim
that oral cancers are now epidemic and report
statistics which are erroneous but which may be
unnecessarily exacerbating fear [32,33]. For
instance, Heck et al.s statement that Cancers of
the head and neck are the fifth most common
cancer worldwide, with more than 600,000 cases
diagnosed each year [33] is incorrect and requires
both context and perspective. According to the
National Cancer Institute, cancers of the head and
neck are extremely rare and the incidence of these
cancers actually declined from a high of 13.21 per
100,000 in 1975 to 10.35 per 100,000 in 2007.
Moreover, an incidence of 600,000 out of a global
population of 6.7 billion is actually a very small
J Sex Med **;**:****
percentage. Although cervical cancer is common
in women [22], head and neck cancers (which are
very rare to begin with) are even rarer among
women [1,29]. Thus, the statement about increas-
ing rates of HPV-related head and neck cancers is
only partially true. The overall incidence of head
and neck cancers decreased in the United States
since 1975, but the proportion of head and neck
cancers that are potentially attributable to HPV
increased [26,29]. One detail often left out is that,
along with the shift in proportion of head and neck
cancers that are related to HPV, the survival rate of
those treated for these cancers has also increased.
This is because the HPV-associated oral cancers
appear to be more responsive to treatment [2].
Head and neck squamous cell carcinomas are
mostly attributed to environmental exposures such
as tobacco use, alcohol consumption, and poor oral
hygiene [34,35]. However, a small proportion (15
20% or an overall incidence rate between 1.55 per
100,000 and 2.07 per 100,000) of these rare head
and neck squamous cell carcinomas occur in non-
smokers and nondrinkers, suggesting the presence
of other risk factors [35]. Recent epidemiologic
and molecular data implicate HPV, particularly
HPV 16, in these cancers; HPV 16 is the strain
most commonly implicated in cervical cancer
[2,32,33,3543]. Earlier researchers hypothesized
that tobacco and alcohol might have a synergistic
effect with HPV in these cancers. However, con-
trolled studies have, to date, failed to provide
support for this theory.
Lifetime number of sexual partners, oral sex
partners, and history of oralanal contact did,
however, differentiate increased risk between
HPV-positive and HPV-negative cancers [43].
Oral or head and neck cancers are higher among
those who have many sexual partners, among those
who are immunocompromisedthose with
acquired immunodeficiency syndrome (AIDs),
those who are human immunodeficiency virus
(HIV) positive, and organ transplant recipients on
immunosuppressant drugs [4446].
Another risk factor for head and neck cancer
among patients younger than age 55 appears to be
long-term marijuana use [47]. One study that
failed to show a relationship between ever using
marijuana and head and neck cancers overall did
show a relationship between head and neck
cancers with prolonged (20 years or more) mari-
juana use [48]. Moreover, there appears to be a
differential effect of marijuana use on the specific
subtype of HPV-positive head and neck cancers
[42]. This suggests that marijuana use may sup-
Caution in the Narrative about HPV and Oral Sex Is Indicated
press some aspect of immune function in ways that
interfere with the bodys ability to clear high-risk
HPV infections, leading to the subsequent devel-
opment of this particular subtype of head and neck
cancers. Researchers recently demonstrated
experimentally (with mice) the mechanism by
which THC, the active ingredient in marijuana,
suppresses the immune system to promote car-
cinogenesis in specific cases:
Studies from our laboratory suggest that cannabinoids are a
double-edged sword. On one hand, cannabinoids can suppress
malignancies of the immune system by inducing apoptosis of
tumors that express cannabinoid receptors. On the other
hand, because they suppress anti-tumor immune response,
they promote growth and metastasis of cannabinoid receptor-
deficient tumors such as breast cancer that are resistant to
cannabinoid-induced apoptosis [49].
Thus, while marijuana may be medicinal in
some instances and promote the suppression of
some kinds of cancers, it clearly interferes with the
immune system and promotes the development of
other kinds of cancers.
Finally, one aspect of immune functioning that
is rarely mentioned in the mainstream medical lit-
erature has to do with negative emotions such as
stress (anxiety, worry, fear, role strain, financial
strain, work expectations that exceed resources,
etc.) depression, or bereavement. The effect of
chronic negative emotions on immune functioning
and hence, indirectly, on vulnerability to other
kinds of disease is well documented in the litera-
ture on psychoneuroimmunology [5052]. While
physicians quickly assess for chronic illnesses and
known medical vulnerabilities in new patients,
chronic life difficulties such as caring for a sick
family member or handicapped child, poverty,
social marginalization, living with an abusive
spouse, or countless other unrelenting stressors
might easily escape notice in a routine visit. Very
little research has been done to elucidate the pos-
sible role of chronic stress and attendant negative
emotions in the oncogenesis in HPV-related
cancers [53,54]. And yet, chronic stress, pessi-
mism, and sleep disturbance are known to have
deleterious effects on immune functioning and can
tip the body toward disease [55]. So, while popular
press, social networking media, and several high
profile cases of oral cancers have joined to create a
narrative attributing oral cancer to oral sex, the
truth is more ambiguous, more complex, and more
nuanced.
Sexual Transmission of HPV
HPV is most commonly known to cause warts, and
warts can be transmitted from hands to genitals
5
although the strains of HPV that cause warts are
not the same strains that cause cancer [56]. While
HPV is thought to be transmitted sexually, it is
clear that HPV can be transmitted nonsexually as
well [28,56,57]. In their 1998 article, Edwards and
Carne reviewed the literature on the transmission
of viral sexually transmitted infections. They
found that the evidence favoring oral transmission
of HPV is both based on case studies and is only
correlational evidence. Thus, many questions are
left unanswered. In order for an HPV infection to
become persistent, other factors are necessary. In
order for a persistent HPV infection to become
carcinogenic, even more factors are necessary and,
while these remain mostly unknown, it is thought
that these probably involve compromises to the
immune system [33,58]. The link between oral sex,
HPV, and cancer is not a simple cause and effect
relationship.
Data from the U.S. Center for Disease Control
(CDC) show that both cunnilingus and fellatio are
widely practiced sexual behaviors. In a large
(N = 12,571) survey known conducted by the CDC
in 2002, 90% of male respondents and 88% of
female respondents reported having had oral sex
with an opposite sex partner [59]. Similarly,
research from other cultures shows oral sexual
contact to be very common, and oral genital contact
is more common than anal intercourse among gay
and bisexual men [60,61]. It must be noted that
when base rates of a behavior are very high, corre-
lations between behavior and vanishingly small
outcomes are rendered to be virtually meaningless.
While there is little evidence that HPV-related
cancers are caused by oral sex per se, narratives
promoted in tabloids fuel fears in the popular
imagination and many patients come seeking
therapy, information, tests, or vaccines in hope of
allaying their fears. However, vaccines are preven-
tative not therapeutic. Moreover, the HPV vac-
cines have been studied on a younger population
because their efficacy is greatest when adminis-
tered before onset of sexual activity, and in any
case the vaccines are useless for those who have
already been infected by vaccine-relevant HPV
genotypes [62]. Moreover, a small subset of clinical
trial data even showed that vaccination of women
already battling a persistent infection of a vaccine-
relevant HPV may actually promote carcinogen-
esis [63,64].
Detection and Classification of HPV
The HPV tests on the market only help doctors
screen patients for cervical cancer. There is no
J Sex Med **;**:****
6 Rosenquist
general test for men or women to check overall
HPV status nor is there an HPV test that can
detect whether HPV is on the genitals or in the
mouth or throat. Moreover, the tests for detecting
and assessing the DNA of different strains of HPV
that are available to clinicians in medical practice
differ from those available to researchers: the tests
available to practitioners are not as reliable or as
accurate as are the tests that are available to
researchers. The test available to clinicians is
called the HC2 test [6567] and is only used for
detecting and classifying HPV from cervical
samples in women. According to the manufac-
turer, Qiagen, The digene HC2 HPV DNA Test
is an in vitro nucleic acid hybridization assay with
signal amplification using microplate chemilumi-
nescence for the qualitative detection of 18 types
of HPV DNA in cervical specimens. The digene
HC2 HPV DNA Test can differentiate between
two HPV DNA groups, low- and high-risk types
[68]. The HPV tests on the market only help
doctors screen patients for the presence of a group
of HPVs that may cause cellular changes, which
may lead to cervical cancer in some patients if not
treated. These commercial test kits are designed to
screen 13 high-risk HPV genotypes out of about
40 genotypes commonly found in the anogenital
regions of women and men. Unlike the technology
used for HPV research, these commercial test kits
do not reliably determine the HPV genotype after
detection and are associated with up to 25% false-
negative results when cervical precancer is used as
the criteria for evaluation [67]. One of the Food
and Drug Administration (FDA)-approved HPV
tests has been found to generate two to four times
more positive results than the other [69]. This
error rate was, in the past, acceptable in clinical
settings, where the more important diagnostic
questions were answered in follow-up with Papa-
nicolaou (PAP) smears or colposcopy.
If a virology-based technology is used for
primary screening for the prevention of cervical
cancer or HPV-based oral cancer, the HPV detec-
tion test must be highly sensitive with extremely
low false-negative rates, and it must be followed
with an extremely reliable HPV genotyping
method to determine the HPV genotype for
follow-up of the patients with persistent HPV
infection, a necessary factor leading to cervical
precancer or cancer. The technology that is con-
sidered essential for research purposes is the more
sophisticated polymerase chain reaction (PCR)
amplification, followed by nucleic acid-based HPV
genotyping because this test is much more specific
J Sex Med **;**:****
and much more accurate [70]. Now both the FDA
[71] and the National Cancer Institute (NCI) [72]
have acknowledged that PCR detection followed
by DNA sequencing is the standard method for
reliable HPV genotyping in clinical specimens as
well. However, DNA sequencing-based HPV
genotyping is not widely used in clinical laborato-
ries because the FDA has classified HPV testing as
class III cancer tests for regulation [58]. The
latter classification makes it extremely difficult for
medical device manufacturers to assemble a test kit
for commercial distribution because scientifically
it is almost impossible to use a cancer end point to
validate a virology test. However, the recent devel-
opment of vaccines against HPVand the impli-
cation of HPV in other kinds of cancers that might
be sexually transmittedmakes it more important
for a wider group of patients to know how to
accurately detect HPV [70,73].
Conclusion
Head and neck cancerscancers that encompass a
wide range of specific anatomical sites, including
cancers of the oral cavity, tongue, tonsils, pharynx,
etc.are exceedingly rare overall and have
declined since 1975. However, a specific subset of
HPV-positive head and neck cancers has increased
among a younger cohort, leading to much scientific
and popular speculation about why. Because HPV
may be sexually transmitted and because the spe-
cific subtype of head and neck cancers that have
increased among younger subjects is not only HPV
positive but also the same strains that are known to
cause cervical cancer, speculation has centered on
sexual behaviorsspecifically on oral genital
contact. However, the natural life cycle of HPV, the
natural waxing and waning of HPV infections
throughout the life span and between partners in a
monogamous couple, along with the frequent lack
of correlation between oral and genital HPV infec-
tions within individuals and between partners, sug-
gests that something more must be at play.
Indeed, HPV-related cancers require compro-
mise of the natural virus clearing functions of a
healthy immune system in order to proliferate.
Some such factors are related to sexual
behaviorspecifically the number of sexual part-
ners one has had or ones partner has had. Some
factors have to do with immune compromise such
as AIDS or HIV-positive status, chronic smoking,
or heavy alcohol use. Moreover, other factors are
neither sexual nor behavioral, such as immunosup-
pressant therapy secondary to organ transplant.
Caution in the Narrative about HPV and Oral Sex Is Indicated
Additionally, a surprising role for marijuana use
has emerged. While infrequent, casual marijuana
use was not associated with an increased risk for
HPV-related head and neck cancers, prolonged
use was associated with greater risk.
HPV should not be a cause for concern among
monogamous couples with a rich and varied sex life,
as long as the sexual system remains closed and other
immune compromising factors are not present.
HPV becomes a concern in the context of immune
system compromise and infection persistence. Thus,
the persistence of any (oral or genital) HPV infection
in one partner raises the risk of persistent HPV
infection in the other partner. The immune system is
most readily compromised when there are other risk
factors such as HIV infection or organ transplant
with immune suppressant therapy. Other long-term
risk factors include multiple or many serial partners,
long-term (more than 5 years) use of oral contracep-
tives, and prolonged (20+ years) use of marijuana,
and a host of other variables. The role of other
potential risk factors such as prolonged exposure to
unrelenting stress and/or negative emotions has not
yet been determined. Thus, while vaccinating chil-
dren and adolescents who have not yet been infected
with HPV may be a useful preventative strategy for
this cohort, young people who are not yet sexually
active should also be made aware that HPV can be
transmitted orally through kissing and oral sex as
well as through genital and anal intercourse. Sexually
active adults are more likely to benefit from healthy
lifestyles that promote good immune functioning
coupled with regular medical checkups aimed at
early detection and treatment.
Corresponding Author: Sara E. Rosenquist, PhD, 417
Overland Drive, Chapel Hill, NC 27517, USA. Tel:
9199333987; Fax: 9199330611; E-mail: DrSara@
DrSara.com
Conflict of Interest: None.
Statement of Authorship
Category 1
(a) Conception and Design
Sara E. Rosenquist; Michael Perelman
(b) Acquisition of Data
Sara E. Rosenquist
(c) Analysis and Interpretation of Data
Sara E. Rosenquist
Category 2
(a) Drafting the Article
Sara E. Rosenquist
7
(b) Revising It for Intellectual Content
Sara E. Rosenquist & Anonymous Reviewers
Category 3
(a) Final Approval of the Completed Article
Sara E. Rosenquist & Anonymous Reviewers
References
1 Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R,
Waldron W, Edwards BK. Seer cancer statistics review. In:
Institute NC, ed. Bethesda, MD; 2010:19752007.
2 Chaturvedi AK, Engels EA, Anderson WF, Gillison ML. Inci-
dence trends for human papillomavirusrelated and unrelated
oral squamous cell carcinomas in the United States. J Clin
Oncol 2008;26:6129.
3 Tjiong MY, Out TA, terSchegget J, Burger MPM, van der
Vange N. Epidemiologic and mucosal immunologic aspects of
HPV infection and HPV-related cervical neoplasia in the
lower female genital tract: A review. Int J Gynecol Cancer
2001;11:917.
4 Maden C, Beckmann AM, Thomas DB, McKnight B,
Sherman KJ, Ashley RL, Corey L, Daling JR. Human papil-
lomaviruses, herpes simplex viruses, and the risk of oral cancer
in men. Am J Epidemiol 1992;135:1093102.
5 Syrjnen S. Human papillomaviruses in head and neck carci-
nomas. N Engl J Med 2007;356:19935.
6 Huang LW, Seow KM. Oral sex is a risk factor for human
papillomavirus-associated nasopharyngeal carcinoma in hus-
bands of women with cervical cancer. Gynecol Obstet Invest
2010;70:735.
7 Louvanto K, Rintala Marjut A, Syrjnen Kari J, Grnman Seija
E, Syrjnen Stina M. Genotype-specific persistence of genital
human papillomavirus (HPV) infections in women followed
for 6 years in the Finnish Family HPV Study. J Infect Dis
2010;202:43644.
8 Doorbar J. Papillomavirus life cycle organization and biomar-
ker selection. Dis Markers 2007;23:297313.
9 Wallin K, Wiklund F, Angstrom T, Bergman F, Stendahl U,
Wadell G, Hallmans G, Dillner J. Type-specific persistence of
human papillomavirus DNA before the development of inva-
sive cervical cancer. N Engl J Med 1999;341:16338.
10 Cuschieri K, Cubie H, Whitley M, Gilkison G, Arends M,
Graham C, McGoogan E. Persistent high risk HPV infection
associated with development of cervical neoplasia in a prospec-
tive population study. J Clin Pathol 2005;58:94650.
11 Brummer O, Hollwitz B, Bohmer G, Kuhnle H, Petry K.
Human papillomavirus-type persistence patterns predict the
clinical outcome of cervical intraepithelial neoplasia. Gynecol
Oncol 2006;102:51722.
12 Constandinou-Williams C, Collins SI, Roberts S, Young LS,
Woodman CBJ, Murray PG. Is human papillomavirus viral
load a clinically useful predictive marker? A longitudinal study.
Cancer Epidemiol Biomarkers Prev 2010;19:8327.
13 Johnson T, Bryder K, Corbet S, Fomsgaard A. Routine geno-
typing of human papillomavirus samples in Denmark. APMIS
2003;111:398404.
14 Speich N, Schmitt C, Bollmann R, Bollmann M. Human pap-
illomavirus (HPV) study of 2916 cytological samples by PCR
and DNA sequencing: Genotype spectrum of patients from the
west German area. J Med Microbiol 2004;53:1258.
15 Schiff M, Becker TM, Masuk M, Asselt-King L, Wheeler CM,
Altobelli KK, North CQ, Nahmias AJ. Risk factors for cervical
intraepithelial neoplasia in Southwestern American Indian
women. Am J Epidemiol 2000;152:71626.
J Sex Med **;**:****
 8 Rosenquist
16 Trimble CL, Piantadosi S, Gravitt P, Ronnett B, Pizer E, Elko
A, Wilgus B, Yutzy W, Daniel R, Shah K, Peng S, Hung C,
Roden R, Wu TC, Pardoll D. Spontaneous regression of high-
grade cervical dysplasia: Effects of human papillomavirus type
and HLA phenotype. Clin Cancer Res 2005;11:471723.
17 Mammas I, Sourvinos G, Spandidos D. Human papilloma
virus (HPV) infection in children and adolescents. Eur J
Pediatr 2009;168:26773.
18 Smith EM, Ritchie JM, Yankowitz J, Swarnavel S, Wang D,
Haugen TH, Turek LP. Human papillomavirus prevalence
and types in newborns and parents: Concordance and modes of
transmission. Sex Transm Dis 2004;31:5762.
19 Allen AL, Siegfried EC. The natural history of condyloma in
children. J Am Acad Dermatol 1998;39:9515.
20 Summersgill KF, Smith EM, Levy BT, Allen JM, Haugen TH,
Turek LP. Human papillomavirus in the oral cavities of chil-
dren and adolescents. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod 2001;91:629.
21 Cason J, Mant CA. High-risk mucosal human papillomavirus
infections during infancy & childhood. J Clin Virol 2005;32:
528.
22 Walboomers JMM, Jacobs MV, Manos MM, Bosch FX,
Kummer JA, Shah KV, Snijders PJ, Peto J, Meijer CJ, Muoz
N. Human papillomavirus is a necessary cause of invasive cer-
vical cancer worldwide. J Pathol 1999;189:129.
23 Burk R, Chen Z, VanDoorslaer K. Human papillomaviruses:
Genetic basis of carcinogenicity. Public Health Genomics
2009;12:28190.
24 Castellsagu X, Bosch FX, Muoz N. Environmental
co-factors in HPV carcinogenesis. Virus Res 2002;89:1919.
25 Woodman CBJ, Collins S, Winter H, Bailey A, Ellis J, Prior P,
Yates M, Rollason TP, Young LS. Natural history of cervical
human papillomavirus infection in young women: A longitu-
dinal cohort study. Lancet 2001;357:18316.
26 Syrjnen K. Mechanisms and predictors of high-risk human
papillomavirus (HPV) clearance in the uterine cervix. Eur J
Gynaecol Oncol 2007;28:33751.
27 Kero K, Rautava J, Syrjnen K, Grenman S, Syrjnen S.
Human papillomavirus genotypes in male genitalia and their
concordance among pregnant spouses participating in the
Finnish Family HPV Study. J Sex Med 2011;8:252231.
28 Rintala M, Grnman S, Puranen M, Syrjnen S. Natural
history of oral papillomavirus infections in spouses: A prospec-
tive Finnish HPV Family Study. J Clin Virol 2006;35:8994.
29 World Health Organization Section of Cancer Information.
International association for research on cancer (IARC). Lyon,
France: World Health Organization; GLOBOCAN, 2008.
30 Bosch FX, de Sanjos S. The epidemiology of human papillo-
mavirus infection and cervical cancer. Dis Markers 2007;23:
21327.
1 31 Castellsagu X, Ghaffari A, Daniel RW, Bosch FX, Muoz N,
Shah KV. Prevalence of penile human papillomavirus DNA in
husbands of women with and without cervical neoplasia: A
study in Spain and Colombia. J Infect Dis 1997;176:35361.
32 Marur S, DSouza G, Westra WH, Forastiere AA. HPV-
associated head and neck cancer: A virus-related cancer epi-
demic. Lancet Oncol 2010;11:7819.
33 Heck JE, Berthiller J, Vaccarella S, Winn DM, Smith EM,
Shangina O, Schwartz SM, Purdue MP, Pilarska A, Eluf-Neto
J, Menezes A, McClean MD, Matos E, Koifman S, Kelsey KT,
Herrero R, Hayes RB, Franceschi S, Wnsch-Filho V,
Fernndez L, Daudt AW, Curado MP, Chen C, Castellsagu
X, Ferro G, Brennan P, Boffetta P, Hashibe M. Sexual behav-
iours and the risk of head and neck cancers: A pooled analysis
in the International Head and Neck Cancer Epidemiology
(INHANCE) consortium. Int J Epidemiol 2010;39:16681.
34 Lissowska J, Pilarska A, Pilarski P, Samolczyk-Wanyura D,
Piekarczyk J, Bardin-Mikollajczak A, Zatonski W, Herrero R,
J Sex Med **;**:****
Munoz N, Franceschi S. Smoking, alcohol, diet, dentition and
sexual practices in the epidemiology of oral cancer in Poland.
Eur J Cancer Prev 2003;12:2533.
35 Gillison ML, Koch WM, Capone RB, Spafford M, Westra
WH, Wu L, Zahurak ML, Daniel RW, Viglione M, Symer
DE, Shah KV, Sidransky D. Evidence for a causal association
between human papillomavirus and a subset of head and neck
cancers. J Natl Cancer Inst 2000;92:70920.
36 Syrjanen S. The role of human papillomavirus infection in
head and neck cancers. Ann Oncol 2010;21(suppl 7):
vii2435.
37 Thariat J, Badoual C, Faure C, Butori C, Marcy PY, Righini
CA. Basaloid squamous cell carcinoma of the head and neck:
Role of HPV and implication in treatment and prognosis. J
Clin Pathol 2010;63:85766.
38 Morshed K. Association between human papillomavirus infec-
tion and laryngeal squamous cell carcinoma. J Med Virol
2010;82:101723.
39 DSouza G, Kreimer AR, Viscidi R, Pawlita M, Fakhry C,
Koch WM, Westra WH, Gillison ML. Casecontrol study of
human papillomavirus and oropharyngeal cancer. N Engl J
Med 2007;356:194456.
40 Gillison M. Human papillomavirus-related diseases: Orophar-
ynx cancers and potential implications for adolescent HPV
vaccination. J Adolesc Health 2008;43(suppl 1):S5260.
41 Gillison ML, Chaturvedi AK, Lowy DR. HPV prophylactic
vaccines and the potential prevention of noncervical cancers in
both men and women. Cancer 2008;113(suppl):303646.
42 Gillison ML, DSouza G, Westra W, Sugar E, Xiao W, Begum
S, Viscidi R. Distinct risk factor profiles for human papilloma-
virus type 16positive and human papillomavirus type
16negative head and neck cancers. J Natl Cancer Inst
2008;100:40720.
43 Adelstein DJ, Ridge JA, Gillison ML, Chaturvedi AK, DSouza
G, Gravitt PE, Westra W, Psyrri A, Kast WM, Koutsky LA,
Giuliano A, Krosnick S, Trotti A, Schuller DE, Forastiere A,
Ullmann CD. Head and neck squamous cell cancer and the
human papillomavirus: Summary of a national cancer institute
state of the science meeting, November 910, 2008, Washing-
ton, DC. Head Neck 2009;31:1393422.
44 Chaturvedi AK, Madeleine MM, Biggar RJ, Engels EA. Risk of
human papillomavirusassociated cancers among persons with
AIDS. J Natl Cancer Inst 2009;101:112030.
45 Kreuter A, Wieland U. Human papillomavirus-associated dis-
eases in HIV-infected men who have sex with men. Curr Opin
Infect Dis 2009;22:10914.
46 Grulich AE, vanLeeuwen MT, Falster MO, Vajdic CM. Inci-
dence of cancers in people with HIV/AIDS compared with
immunosuppressed transplant recipients: A meta-analysis.
Lancet 2007;370:5967.
47 Zhang Z-F, Morgenstern H, Spitz MR, Tashkin DP, Yu G-P,
Marshall JR, Hsu TC, Schantz SP. Marijuana use and
increased risk of squamous cell carcinoma of the head and
neck. Cancer Epidemiol Biomarkers Prev 1999;8:10718.
48 Berthiller J, Lee Y-CA, Boffetta P, Wei Q, Sturgis EM, Green-
land S, Morgenstern H, Zhang ZF, Lazarus P, Muscat J, Chen
C, Schwartz SM, Eluf Neto J, Wnsch Filho V, Koifman S,
Curado MP, Matos E, Fernandez L, Menezes A, Daudt AW,
Ferro G, Brennan P, Hashibe M. Marijuana smoking and the
risk of head and neck cancer: Pooled analysis in the
INHANCE consortium. Cancer Epidemiol Biomarkers Prev
2009;18:154451.
49 Hegde VL, Nagarkatti M, Nagarkatti PS. Cannabinoid recep-
tor activation leads to massive mobilization of myeloid-derived
suppressor cells with potent immunosuppressive properties.
Eur J Immunol 2010;40:335871.
50 Gror M, Meagher MW, Kendall-Tackett K. An overview of
stress and immunity. In: Kendall-Tackett K, ed. The psycho-
Caution in the Narrative about HPV and Oral Sex Is Indicated
neuroimmunology of chronic disease: Exploring the links
between inflammation, stress, and illness. Washington, DC:
American Psychological Association; 2010:922.
51 Forlenza MJ, Baum A. Psychoneuroimmunology. In: Boll TJ,
Frank RG, Baum A, Wallander JL, eds. Handbook of clinical
health psychology: Volume 3. Models and perspectives in
health psychology. Washington, DC: American Psychological
Association; 2004:81114.
52 Kiecolt-Glaser JK, McGuire L, Robles TF, Glaser R. Psycho-
neuroimmunology: Psychological influences on immune
function and health. J Consult Clin Psychol 2002;70:537
47.
53 Jensen SE, Lehman B, Antoni MH, Pereira DB. Virally medi-
ated cervical cancer in the iatrogenically immunocompro-
mised: Applications for psychoneuroimmunology. Brain Behav
Immun 2007;21:75866.
54 Pereira DB, Antoni MH, Danielson A, Simon T, Efantis-
Potter J, Carver CS, Durn RE, Ironson G, Klimas N,
OSullivan MJ. Life stress and cervical squamous intraepithe-
lial lesions in women with human papillomavirus and human
immunodeficiency virus. Psychosom Med 2003;65:42734.
55 Segerstrom SC, Miller GE. Psychological stress and the
human immune system: A meta-analytic study of 30 years of
inquiry. Psychol Bull 2004;130:60130.
56 Edwards S, Carne C. Oral sex and the transmission of viral
STIs. Sex Transm Infect 1998;74:610.
57 Pao CC, Tsai PL, Chang YL, Hsieh TT, Jin JY. Possible
non-sexual transmission of genital human papillomavirus
infections in young women. Eur J Clin Microbiol Infect Dis
1993;12:2212.
58 Lee SH. Reclassification petition: Human papillomavirus
(HPV) DNA nested polymerase chain reaction (PCR) detec-
tion devise (K063649). In: Health CfDaR, editor. Washington,
DC, 2007:68.
59 Mosher WD, Chandra A, Jones J. Sexual behavior and selected
health measures: Men and women 1544 years of age, United
States, 2002. In: Prevention CfDCa, editor. Advance Data From
Vital and Health Statistics. Hyattsville, Maryland 20782, USA,
2005: 56 pp.
60 Rosenberger JG, Reece M, Schick V, Herbenick D, Novak
DS, Van Der Pol B, Fortenberry JD. Sexual behaviors and
situational characteristics of most recent male-partnered sexual
event among gay and bisexually identified men in the United
States. J Sex Med 2011;8:304050.
61 Ortiz AP, Soto-Salgado M, Surez E, del Carmen Santos-
Ortiz M, Tortolero-Luna G, Prez CM. Sexual behaviors
among adults in Puerto Rico: A population-based study. J Sex
Med 2011;8:243949.
62 Hildesheim A, Herrero R, Wacholder S, Rodriguez AC,
Solomon D, Bratti MC, Schiller JT, Gonzalez P, Dubin G,
Porras C, Jimenez SE, Lowy DR; Costa Rican HPV Vaccine
Trial Group. Effect of human papillomavirus 16/18 L1 viruslike
9
particle vaccine among young women with preexisting infec-
tion. JAMA 2007;298:74353.
63 Garland SM, Hernandez-Avila M, Wheeler CM, Perez G,
Harper DM, Leodolter S, Tang GW, Ferris DG, Steben M,
Bryan J, Taddeo FJ, Railkar R, Esser MT, Sings HL, Nelson
M, Boslego J, Sattler C, Barr E, Koutsky LA; Females
United to Unilaterally Reduce Endo/Ectocervical Disease
(FUTURE) I Investigators. Quadrivalent vaccine against
human papillomavirus to prevent anogenital diseases. N Engl J
Med 2007;356:192843.
64 FDA. VRBPAC background document: Gardisil HPV
quadrivalent vaccine May 18, 2006 meeting: Federal Drug
Administration. 2006.
65 Cope J, Hildesheim A, Schiffman M, Manos M, Lorincz A,
Burk R, Glass AG, Greer C, Buckland J, Helgesen K, Scott
DR, Sherman ME, Kurman RJ, Liaw KL. Comparison of the
hybrid capture tube test and PCR for detection of human
papillomavirus DNA in cervical specimens. J Clin Microbiol
1997;35:22625.
66 Ksel S, Burggraf S, Mommsen J, Engelhardt W, Olgemller
B. Type-specific detection of human papillomaviruses in a
routine laboratory settingImproved sensitivity and specific-
ity of PCR and sequence analysis compared to direct hybridi-
sation. Clin Chem Lab Med 2003;41:78791.
67 Lonky N, Felix J, Naidu Y, Wolde-Tsadik G. Triage of atypical
squamous cells of undetermined significance with hybrid
capture II: Colposcopy and histologic human papillomavirus
correlation. Obstet Gynecol 2003;101:4819.
68 Gogola J, Van Dinh T, Lucci J, Smith E, Hannigan E. HC2
HPV DNA Test-REF 5199-1220 Digene Corporation, Gaith-
ersburg, MD 20878 USA. Human papillomavirus testing for
triage in a referral population. J Low Genit Tract Dis
2005;5:2932.
69 Kinney W, Stoler MH, Castle PE. Special commentary:
Patient safety and the next generation of HPV DNA tests. Am
J Clin Pathol 2010;134:1939.
70 Lee S, Vigliotti V, Vigliotti J, Pappu S. Routine human papil-
lomavirus genotyping by DNA sequencing in community hos-
pital laboratories. Infect Agent Cancer 2007;2:11.
71 Simon K, Kondratovich M. Draft guidance for industry and
FDA staff: Establishing the performance characteristics of in
vitro diagnostic devices for the detection or detection and
differentiation of human papillomaviruses. In: U.S. Depart-
ment of Health and Human Services FaDA, Center for
Devices and Radiological Health, Office of In Vitro Diagnostic
Device Evaluation and Safety, Division of Microbiology
Devices, editor. Washington, DC, 2009:127.
72 Marino MP, Rasmussen CN. HPV genotyping. In: Health
NIo, editor. Washington, DC, 2010.
73 Syrjnen K. New concepts on risk factors of HPV and novel
screening strategies for cervical cancer precursors. Eur J
Gynaecol Oncol 2008;29:20521.
J Sex Med **;**:****