Table Of ContentHuman Papillomavirus: A Catalyst to a Killer
Alice Richman
ABSTRACT
Genital human papillomavirus (HPV) is the most prevalent and widespread sexually transmitted disease
and is responsible for almost all cases of cervical cancer worldwide. However, HPV has received little public health
attention, is not a reportable STD, and often is absent from the repertoire of STDs. In addition, there is pervasive
misinformation about HPV among health care providers, professionals, patients and the public. This paper pro-
vides a comprehensive literature review of HPV by 1) addressing important epidemiological issues such as HPV
prevalence, contraction, symptoms, transmission, detection, prevention, screening and treatment, 2) addressing
specific gaps in the literature and 3) addressing future steps that can be taken among public health agencies, health
care professionals, health educators and the general public to ensure HPV prevention, detection and treatment.
INTRODUCTION Human Papillomavirus who carry the virus will never know that
Genital human papillomavirus (HPV) HPV is a DNA tumor virus that stems they have it,5 some classic manifestations
is the most prevalent and widespread sexu- from the papovavirus family.4 There are of genital HPV can be detected. Among the
ally transmitted disease (STD),1 causing over 100 different types of HPV.5 In types that affect the genital area, only a
nearly all cases of cervical cancer world- humans, only 40 types are sexually trans- few are tumor-producing, and thus, are con-
wide,2 and is of public health concern. mitted and affect the genital area, and sidered to be high-risk types. For example,
However, HPV has received little public the remainder affect the skin, hands and whereas HPV types 6 and 11 are low-risk
health attention, is not a reportable STD, feet.6 Genital HPV can present itself as geni- genital wart-causing agents and are not
and often is absent from the repertoire of tal warts and as cervical dysplasia. Most associated with cervical cancer, types 16,
STDs. In addition, there is pervasive mis- genital HPV infections subside on their 18, 31 and 45 are high-risk types and,
information about HPV among health care own; however, some infections can have therefore, have potential to develop into
providers, professionals, patients and the serious health consequences. In fact, cervical cancer. 8
public.3 This paper will provide a compre- certain strains of genital HPV are respon-
hensive literature review of HPV by ad- sible for nearly all (99.7%) cases of cervical
dressing important epidemiological issues, cancer worldwide.7 Alice Richman, MPH, BA, is a research assis-
specific gaps in the literature and future Genital HPV is classified as low-, inter- tant and doctoral student at the University of
steps for public health agencies, health care mediate-, and high-risk for cervical cancer. South Florida, 9481 Highland Oak Drive,
professionals, health educators and the gen- Although all types of HPV are largely as- #1611, Tampa, FL 33647; E-mail: arichman@
eral public. ymptomatic, where the majority of people hsc.usf.edu.
166 American Journal of Health Education — May/June 2005, Volume 36, No. 3
Alice Richman
Genital HPV & Cervical Cancer shown to clear up by themselves within two present itself as genital warts for both men
Certain types of genital HPV account for to five years.8 and women or abnormal cells that reside
almost all cases of cervical cancer.2 Cervi- Contracting Genital HPV on the cervix for women. Genital warts vary
cal cancer is the third most common can- Both men and women are at risk for con- in shape and size and can be anywhere from
cer in the world,9 and the tenth most com- tracting genital HPV. Because the primary 1mm to greater than 10mm in size. Genital
mon cancer among women in the United mode of transmission of genital HPV is warts can be raised or flat, or can exist alone
States.10 Whereas an estimated 230,000 through sexual (vaginal, anal and oral) pen- or as multiple warts. They can appear as
deaths occur annually from cervical cancer etration or genital-to-genital contact, cer- flesh-colored or white or they can be present
worldwide, most of these cases (80%) tain sexual practices increase the risk for but undetectable with the naked eye. Non-
occur in developing countries.9 In the past, HPV acquisition.17 Persons with multiple visible warts are referred to as subclinical.
cervical cancer was one of the most com- sexual partners and people who begin In general, warts do not itch or burn.
mon causes of cancer deaths for women sexual activity at a young age are most at Warts can appear on a woman’s vulva, in
in the U.S.; however, the advent of the risk for contracting HPV.8 It also has been or around the vagina, anus or on the groin
Papanicolaou test (Pap test) has allowed shown that people with comorbid factors and cervix. Warts on men can appear on
for early detection of cervical cell changes such as having concurrent STIs are at higher the penis, scrotum, groin, or in and around
and treatment, which has prevented cervi- risk for HPV.18 the anus.21
cal cancer development.11 Immune system response is directly re- Symptoms for HPV that are not wart-
Nonetheless, in 2003, an estimated 4,100 lated to the persistence, spread or remission producing for women includes cervical dys-
deaths resulted from cervical cancer in the of an already-established HPV infection. plasia, which can usually be detected
U.S. and many of these deaths could have Individuals with a suppressed immune sys- through a Pap test. Because most high-risk
been prevented through appropriate screen- tem are more likely to experience a repeti- HPV resides on the cervix and cannot be
ing mechanisms.12 In fact, half of all women tive and active HPV infection.19 It is not detected without screening, screening
who develop cervical cancer in the U.S. have surprising then that women with Human mechanisms are critical to the detection of
not had a Pap test.13 When detected early Immunodeficiency Virus (HIV) are more high-risk HPV and the prevention of cer-
through screening, mortality from cervical likely than HIV-negative women to have vical cancer.21
cancer is controllable.8 HPV and are, therefore, at a higher risk for Genital HPV Transmission
It is unacceptable that over 4,000 women cervical cancer. In fact, women living with As stated previously, the primary mode
are dying from cervical cancer annually in HIV are four times more likely to have HPV of transmission of HPV is through sexual
the U.S. If over 4,000 American civilians than women without HIV.18 intercourse.17 However, HPV can be trans-
were killed this year due to terrorism, this Circumcision in men has been shown mitted person-to-person through any skin-
kind of loss of life would not be tolerated to reduce the likelihood of HPV infection to-skin contact with an HPV-infected area
by the government or the American people. among women. Therefore, the risk of of the body such as the genitals or anus.22 A
Why is it that we tolerate death from cervi- cervical cancer is slightly reduced in female few recent studies have documented the
cal cancer when we know how to prevent partners who engage in sexual activity with transmission of HPV through non-sexual
it? Clearly, more emphasis should be placed circumcised men.18 Another interesting pathways, such as fomites or vertical trans-
on the surveillance, detection and treatment epidemiologic development is the connec- mission.22 One study looked at HPV in vir-
of genital HPV, as no woman should be tion among smoking, HPV and cervical gins and attributed their genital infection
dying of cervical cancer in the U.S. cancer. Once a person already has HPV, to non-sexual pathways.17 Although non-
Prevalence of HPV smoking cigarettes has been shown to be a sexual routes of transmission are deemed
The Association of Reproductive Health catalyst, increasing a person’s risk for cer- less significant than sexual modes of trans-
Professionals (ARHP) estimates that the vical cancer.20 mission, further research in this area is war-
lifetime risk of acquiring HPV is between New studies are being conducted to as- ranted.
75% and 90%.14 It is, therefore, incongru- sess the relationship between a potential Another notable mode of transmission
ent that the lifetime risk is so great yet 70% genetic link that increases a person’s vul- is the passing of HPV from mother to in-
of people have never heard of it.15 It is esti- nerability to HPV. People with this genetic fant during pregnancy23 and childbirth.24
mated that in the United States alone, 24 link may be predisposed to cervical cancer Although literature on this topic is incon-
million people are infected with genital and may, therefore, be at a higher risk.8 clusive, the consensus is that babies can con-
HPV,8 and 5.5 million people become in- Symptoms of Genital HPV tract HPV from the mother in utero.23 How-
fected with genital HPV each year.16 And, There are symptoms associated with ever, the actual mode of in utero trans-
whereas the virus never actually leaves the genital HPV, although in most cases the vi- mission is unclear. It has been suggested that
body, 92% of all HPV infections have been rus is asymptomatic.5 Genital HPV can HPV transmission in utero could occur
American Journal of Health Education — May/June 2005, Volume 36, No. 3 167
Alice Richman
through semen at fertilization, through an cination will not only prevent genital warts follow-up with a similar Pap test in one cal-
infection from the mother,23 through the but also will prevent over 70% of dyspla- endar year.21 This type of Pap test has
placenta or through the process of vaginal sias and cancers, greatly reducing the been shown to be 70% to 80% sensitive in
birth.25 costs associated with HPV detection and detecting HPV.32
The influence of mode of delivery in treatment.28 In addition, McNeil postulates The second method used is a liquid-
childbirth on HPV transmission is an ad- that because HPV is present in almost all based Pap test called a Thin Prep™ where
ditional area that requires further research. cases of cervical cancer, effective vaccina- cells are sampled from the cervix and then
Some studies show that babies are less likely tion could eliminate cervical cancer world- placed in a container filled with a liquid
to acquire HPV through cesarean section wide.29 Moreover, if vaccination proves to solution. If results are normal from this type
delivery compared to vaginal delivery,26 be effective, projected challenges include of test, the recommendation is to test again
whereas other studies show that amniotic vaccine delivery, vaccine awareness and with a similar Pap test in two calendar years.
fluid in utero can transmit HPV, and there- destigmatization of the concept of HPV.5 The longer period of time for this second
fore, a cesarean birth does not offer any Sanders and Taira evaluated the cost-ef- test is due to the higher accuracy of the liq-
protective factors.27 More research is needed fectiveness of vaccinating female teens uid-based test.21 The liquid-based test has
to sift through these inconsistencies. How- against high-risk HPV.30 They found the been shown to be 85% to 95% sensitive in
ever, it is important to understand routes vaccination of adolescent girls to be cost- detecting HPV.33
of transmission, especially in conjunction effective when compared to other health The third method, a combination Pap-
with new vaccination program planning interventions. The particular high-risk HPV HPV DNA test, is used only to test women
and implementation. vaccine used in this study prevented a sub- over the age of 30. If results are normal, then
Genital HPV Prevention stantial number of lifetime cases of HPV new recommendations suggest that women
The main way to avoid HPV is not to and cervical cancer and, by implication, a can wait three years before undergoing an-
engage in sexual intercourse or skin-to-skin large number of cancer-related deaths. other screen.21 The induction of screening
contact with a HPV-infected person. But, Sanders and Taira project that an effec- mechanisms for HPV has proven invaluable
because the majority of people are sexually tive vaccination could prevent 1,300 cervi- in that these screening methods have been
active at some point in their lives, there are cal cancer-related deaths annually in attributed to a 70% decrease in cervical can-
ways to reduce the risk of acquiring HPV the U.S. if all 12-year-old girls residing in cer deaths over the last 50 years.34
when sexually active. Having only one the U.S. were given the vaccination.30 This Another method used for screening for
sexual partner reduces the risk of HPV. Us- analysis by Sanders and Taira is one of genital warts for both men and women is
ing condoms correctly can help prevent the only two cost-effective analyses on a HPV through acetowhitening or a highlighting
spread of HPV, although this method of vaccine. The only other study on cost- of HPV lesions with acetic acid (vinegar).
protection is not 100% effective.21 effectiveness was published by the Institute With this method, acetic acid is placed on
One new and currently unfolding HPV of Medicine (IOM) and offered similar cost- the genitals, causing warts to give a white
prevention strategy is vaccination. Vaccines effective results.31 However, because the appearance allowing the HPV to be detected
work through a targeting of proteins in vaccine may not provide immunity for all and typed.21,22 However, American Social
HPV to eradicate infection.8 The results of types of HPV and may not be 100% effec- Health Association warns that this type of
a recent randomized double-blind study tive, vaccination should not replace other screening can be misleading as acetic acid
prevention strategies such as Pap tests and
indicated that a vaccine provided protection may highlight normal bumps on the geni-
of HPV type 16 in a group of 2,392 women protective sexual practices. tals as well.21
aged 16-23.28 This finding indicates that Genital HPV Detection A limitation of existing screening
immunizing women who do not have type The primary mode of detection of HPV mechanisms is that tests available for men
16 HPV could potentially decrease the in- in women is through Pap tests. According are highly inadequate. As Schiffman and
cidence of cervical cancer.28 Larger studies to the American Social Health Association, Castle confirm, “there is currently no reli-
are awaited to prove vaccination success there are currently three ways to screen for able way of measuring HPV infection of the
among HPV types 6, 11, 16, and 18.5 How- genital HPV.21 The first and most common entire cornified epithelium of the penis.”22
ever, because there are so many different method for screening is utilizing the con- Because it is difficult to get a sufficient cell
types of HPV and because HPV is known ventional Pap test to look for abnormal cells. sample from the thick skin of the penis,
for its slow and ever-changing nature, vac- This procedure involves retrieving a sample HPV tests for men tend to produce a cer-
cine research and vaccine success are slow of cells taken from the cervix and subse- tain percentage of false negatives.21 More-
and lengthy processes.8 quently placing the cells on glass to be over, because HPV is so frequently a sub-
Koutsky et al. postulate that if future viewed under a microscope. If results are clinical virus, most men do not know that
vaccines do as well as current vaccines, vac- normal, the recommendation is to conduct they have it, and can infect their partners
168 American Journal of Health Education — May/June 2005, Volume 36, No. 3
Alice Richman
unknowingly. Fortunately research has not lines also agree that women with a total ment option is to have a laser procedure to
shown any great risks for men with HPV hysterectomy for benign indications could remove abnormal cells. However, the laser
that compare to cancer in women. However, discontinue screening. option is used infrequently as not all clini-
further research on screening mechanisms In terms of the use of HPV testing in cians are trained for this type of procedure.21
for men should not be disregarded.21 conjunction with screenings, the ACS rec- Treatment Options for Genital Warts
Pap tests are insufficiently implemented ommends the use of high-risk HPV typing There are various treatment options avail-
to women in the U.S. as demonstrated by following Pap smear results of atypical able for the removal of genital warts. Some
the unacceptable number of deaths (4,100) squamous cells of undetermined signifi- treatment options can be performed at a
as a result of cervical cancer in 2003. Half cance (ASCUS). An ASCUS Pap smear re- physician’s office, whereas others can be
of all women with cervical cancer in the sult means that cells from the cervix were administered at home. Treatment options
U.S. have never had a Pap smear and slightly abnormal. The ACS also recom- for genital warts include the following:
another 10% of women with cervical can- mends a colposcopic evaluation with high- • Cryotherapy: With cryotherapy, warts
cer have not been screened within the past risk HPV and a negative result for HPV can are frozen off with liquid nitrogen. This
five years.13 In addition, another more re- resume annual screening protocol. The procedure is inexpensive but must be per-
cent national survey showed that 18% of ACOG recommends reflex HPV testing as formed by a trained professional.
women in the U.S. have not had a Pap follow-up to ASCUS test results but does • Podophyllin: A chemical compound
smear in the last three years.35 Because Pap not recommend use if the results are LSI that is applied to the wart by a clinician.
tests are a preventative method of discov- (low-grade squamous intraepithelial lesion) However, this treatment option is rarely
ering cervical cancer, every woman should or higher. The USPHSTF discourages the used anymore.
have Pap smears as recommended by the use of HPV testing for primary screening. • Trichloracetic acid (TCA): Acid is ap-
screening guidelines. The Missouri Family Health Council has plied to the wart.
HPV Screening Guidelines created a useful comparative chart of these • Excision of the lesion by a clinician.
In 2003, new screening recommendations three sets of guidelines. The chart is in- • Electrocautery: Warts are burnt off with
for cervical cancer were presented by three cluded as Figure 1. an electrical current.
reputable groups: the American Cancer Treatment Options for • Laser therapy: Laser therapy is costly
Society (ACS), the U.S. Preventive Health Cervical Dysplasia and medical professionals must be well
Services Task Force (USPHSTF), and the Although there is currently no “cure” for trained in the procedure. Most medical pro-
American College of Obstetricians and Gy- HPV, there are various treatment alterna- fessionals do not have laser equipment in
necologists (ACOG).11,36,37 However, the spe- tives for cervical dysplasia. Treatment op- their offices. Laser therapy is most typically
cific recommendations that are advocated tions are enumerated here in no particular used for larger warts or in circumstances
vary slightly across these organizations. order. The first treatment option is for where patients have not succeeded in other
All three guidelines recommend setting women with mild cervical dysplasia to un- treatment procedures.
the age to begin screening at age 21 or three dergo no treatment as 50% to 70% of cases • Interferon is injected into the wart. This
years after onset of sexual activity, which- of mild dysplasia subside on their own.8 A procedure is costly and has side effects that
ever comes first. Whereas ACOG does not second commonly used treatment option have led to it rarely being performed any-
establish an upper age limit for screening, is to have cryotherapy performed. Cryo- more.
ACS and USPHSTF set age limits of age 65 therapy involves freezing the affected cells • Prescription creams such as Podofilox
and 70 respectively as long as women have with liquid nitrogen.21 Cryotherapy is com- cream (Condylox®) and Imiquimod cream
a previous history of normal cytology tests. monly used for its low cost, low complica- (Adlara®). Podofilox cream is applied to
Whereas the ACOG recommends annual tion rate and reliability.8 external warts for four weeks and is rela-
screening intervals for women under 30 re- A third treatment option is to have a tively inexpensive, easy and safe to use.
gardless of screening technology, the ACS loop electrosurgical exision procedure Imiquimod cream is also applied to exter-
recommends annual screening with con- (LEEP) involving a wire loop that becomes nal warts and is easy and safe to use; how-
ventional cytology or every two years with a cutting tool when an electric current is ever, instead of working by destroying warts
liquid-based cytology (i.e., Thin Prep™) passed through it. In this way, clinicians like other treatments, Imiquimod cream
and the USPHSTF recommends screening are able to use this tool to successfully works by boosting the immune system, and
every three years regardless of screening remove lesions.8 thus, suppressing the HPV.
technology. All three groups agree that A fourth treatment option is to have cold Persistence vs. Clearance
screening intervals for women over age 30 conization performed in which a portion HPV persistence refers to the reemer-
should be conducted every 2-3 years based of the cervix that contains the abnormal gence or continuation of a HPV infection
on cytology history. All three sets of guide- cells is removed with a scalpel.8 A fifth treat- after treatment and HPV clearance refers to
American Journal of Health Education — May/June 2005, Volume 36, No. 3 169
Alice Richman
Figure 1. Cervical Cancer Screening Guidelines
A Comparison of Recommendations Compiled by Erin Spears, Clinical Program Coordinator Missouri Family Health Council
Age to begin Age 21, or three years after onset Age 21, or three years after Age 21, or three years
screening of sexual activity onset of sexual activity after onset of sexual
activity
When to discontinue ACOG does not set an upper age Age 65, if they have adequate Age 70, with an intact
screening limit for screening previous screenings and are cervix, and who have
not high risk had 3 consecutive
satisfactory normal/
negative cytology tests.
They must have no
abnormal tests within the
last 10 years
Screening intervals Annually for all women under 30 Annually with conventional At least every three years
regardless of screening technol- cytology or Every two years
ogy (conventional vs. liquid- with a liquid-based cytology
based?
Screening intervals for Women who have had three Every 2-3 years, at the Does not change
women over 30 consecutive negatives screening discretion of the provider, after screening recommenda-
results, and who have no hx of 3 consecutive normal cytology tions for women over 30
CIN 2 or CIN 3, are not results (unless high risk or
immunocompromised, are not immunosuppressed)
HIV infected, and have not had
DES exposure may extend the
screening to every 2-3 years.
Screening intervals for Women who have undergone May discontinue all screenings May discontinue routine
women with total hysterectomy with removal of the (cervical/vaginal) if hysterec- Pap screenings if hyster-
hysterectomy cervix for benign indications and tomy was done for a benign ectomy was done for a
who have no prior history of CIN condition benign condition
2 or CIN 3 or worse may discon-
tinue routine screening
Use of HPV testing in ACOG acknowledges the benefit Recommends the use of high- Discourages use of HPV
conjunction with of reflex HPV testing as a follow- risk HPV typing following an testing for a primary
screenings up to ASC-US test results, but does ASCUS pap. (+) high risk screening. Does not
not advocate using if the results warrants colposcopic evalua- address its use in follow-
are LSIL or higher. FDA has tion, while (-) results can up testing
approved a combo cervical resume annual screening
screening/HPV test for women protocol
a HPV infection that becomes undetectable of HPV, immune suppression and infection mately one year and HPV type 16 tends to
by tests either with or without treatment. with multiple types of HPV.38 Like warts on persist even longer. One of the unresolved
However, little information is available on other parts of the body, warts on the geni- questions about HPV is the issue of viral
why HPV persists in some and subsides in tals tend to subside on their own. HPV on latency. Almost all HPV infections become
others although factors associated with per- the cervix does not always do this, however. undetectable by HPV DNA tests within a
sistence include older age, high-risk types Cervical HPV is detectable for approxi- period of two years except infections that
170 American Journal of Health Education — May/June 2005, Volume 36, No. 3
Alice Richman
lead to precancerous states. More research awareness about HPV prevention, detection public can take to ensure the reduction of
is needed on viral latency as little else is and treatment, which will subsequently save cervical cancer incidence and mortality in
known about what causes reemergence of lives, they can also aid in the decision-mak- the U.S. through the prevention, detection
a HPV infection.22 ing process of picking a treatment option and treatment of HPV.
Public Awareness and HPV and prevention method that is acceptable Public health agencies should collabo-
Public knowledge about HPV is gener- for each individual. In addition, health edu- rate to increase awareness about prevention
ally poor. One U.S. study surveyed all first- cators can play a role in the education of of HPV and cervical cancer among health
year students at a private university and pregnant mothers and supporting fathers care professionals, health educators and the
found that approximately 96% of both on routes of HPV transmission in childbirth public. Outfitted with the current knowl-
males and females had heard of genital and can assist in the decision-making pro- edge about genital HPV, health care profes-
warts, but only 4.2% of males and 11.6% cess for these families. sionals and health educators play an impor-
of females knew that HPV caused genital In the future, when a successful HPV tant role in the promotion of cervical cancer
warts.39 A second study also surveyed uni- vaccination is developed, health educators screening for all women as well as the pro-
versity students and found that in a random will again play an integral part in the edu- motion of preventive measures for both
sample of 500 students, 63% had never cation of the public about the vaccination men and women. In addition, health care
heard of HPV.40 A third study assessed and in facilitating the administration of professionals and health educators can edu-
knowledge among a group of inner-city this important development. As the guide- cate both men and women on methods that
high school students and found that 87% lines on Pap smear screening change, can lower their risk of HPV infection such
had never heard of HPV.41 Other studies health educators can assure that women as monogamy, abstinence, condom and
conducted in the U.S. have found similar are educated on the new screening guide- dental dam use.
low rates of HPV knowledge.42,43,40 lines, thereby making an important com- Public health agencies as well as re-
Low HPV awareness is not only com- mitment to keeping women healthy searchers can ensure that epidemiologic,
mon to people living in the U.S., but also to throughout their lifespan. laboratory and behavioral research is con-
women in the U.K. Among a sample of well- Health educators should work to edu- ducted on HPV infection through the sup-
educated women attending a women’s cate and organize community coalitions port of federal funding. To begin, it would
clinic, 70% had never heard of HPV. Even about HPV, should include current and rel- be helpful to develop a national surveillance
among the 30% who had heard of HPV, evant information in their educational ma- system where genital HPV infections are
fewer than half were able to link HPV to terials, newsletters, public information re- routinely reported. In addition, public
cervical cancer.44 ports and grant writing and should develop health agencies and professionals can work
Implications for Health Educators informational campaigns stressing impor- together to advocate for the speedy devel-
Health educators are a vital component tant HPV prevention messages. While opment of an effective HPV vaccine.
of community health education. They strive health educators raise awareness about As the general public is provided the
to promote and improve healthy lifestyles HPV, they must also remember to simulta- knowledge about genital HPV, they can en-
and prevent disease through a provision of neously decrease the stigma that surrounds sure that they are screened appropriately
information to both individuals and com- HPV. Although health educators must work and that they make informed decisions
munities. In their critical role, health edu- to increase knowledge about HPV, heighten about their sexual health. It is a failure of
cators can influence the level of knowledge public awareness of the threat and conse- the public health and medical system that
and subsequently increase prevention of quences of contracting HPV and increase women continue to die of cervical cancer,
HPV within the community. preventive behaviors among women and as cervical cancer is largely preventable. This
Health educators must first acknowledge men, they can not be expected to do this kind of loss of life is not permissible. How
the vastness of the prevalence of the infec- alone. They will need the help of nurses, many women must die before something is
tion and stress the existence of HPV in their public health social workers, physicians and done? It is time to start caring about HPV.
own work. Further, health educators must other health-related professionals.
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