Human Papillomavirus (HPV)
and Cervical Cancer: An Update on Prevention Strategies Script
August 9, 2005
[1]DANIELS
Hello and welcome to
“Human Papillomavirus (HPV) and Cervical Cancer: An Update on Prevention
Strategies.”
I’m Kysa Daniels, your
moderator for this program, which is originating from the Centers for Disease
Control and Prevention in Atlanta, Georgia.
In this Webcast, we’ll be
discussing genital human papillomavirus (HPV) infection, a sexually transmitted
disease. This is an extremely common infection of growing concern to both the
public and to health care providers.
Our focus today is
- an update on the natural
history of HPV infection,
- the association of different
HPV types with various clinical manifestations,
- HPV transmission, and...
- methods for HPV and
cervical cancer prevention.
Before we introduce our
panelists, let’s hear from CDC Director, Dr. Julie Gerberding.
DR. JULIE GERBERDING:
Hello! I am Dr. Julie Gerberding, Director of the Centers
for Disease Control and Prevention.
Thanks for joining us for this very important webcast on Human Papilloma Virus.
Genital infection with HPV
is the most common sexually transmitted infection in the United States. About 20 million Americans are currently
infected with the virus, and about 6.2 million people become newly infected
each year.
Most infections cause no
clinical problems and go away on their own without treatment. But some
infections lead to genital warts in men and women, and cervical cancer in women.
Although a vaccine against
HPV is in development, there is no curative treatment for genital HPV infection. Treatments are
available for the abnormalities caused by HPV infection.
Persistent infection with
certain types of HPV is a leading cause of cervical cancer. Progression from HPV infection to invasive cancer is a slow process, estimated to take 10-15 years or longer.
Cervical cancer is an uncommon consequence
of HPV infection. Nevertheless, regular screening for cancer with Pap tests can
detect cervical abnormalities that can be treated before they become cancerous. Screening also helps detect cancer at an early
stage where it can be cured in over 90 percent of people.
In the past 40 years, widespread
cervical cancer screening using the Pap test and treatment of precancerous cervical abnormalities have resulted
in a dramatic decrease in the incidence and mortality due to cervical cancer in
the United States.
However, each year in the
U.S., more than 10,000 women still develop cervical cancer and over 3,000 women
die from it. Sadly, of women in the U.S. who develop cervical cancer, about
half have never had a Pap test.
For this reason, CDC established
an HPV and cervical cancer workgroup that
involves scientists from four of CDC's 12 national centers. The workgroup
helps us bring our best experts together so we can have more impact on this important health threat.
This Webcast focuses on
the prevention of genital HPV infection in men and women. It summarizes key aspects
of the epidemiology of HPV infection and its transmission, and discusses the
best strategies to prevent HPV infections and its associated diseases. This
knowledge can help support the action that we must take to decrease the threat
of HPV and protect women and men from the preventable diseases it causes. Thank you.
Thank you, Dr. Gerberding. Now it’s time to introduce our guests for
today’s program.
Dr. John Douglas is the
Director of the Division of Sexually Transmitted Disease Prevention of the National
Center for HIV, STD, & TB Prevention at CDC.
Dr. Mona Saraiya is a
medical epidemiologist working in the Epidemiology and Applied Research Branch
of the Division of Cancer Prevention and Control at the National Center for Chronic
Disease Prevention and Health Promotion at CDC.
And Dr. Tom Wright is
Associate Professor of Pathology at the College of Physicians and Surgeons at Columbia
University. Welcome to all of you.
Before we begin, allow me
to go over a few details about today’s program.
This program will be available
for viewing at the program website at www.phppo.cdc.gov/PHTN/HPV-05.
We will be offering continuing
education credits for various professions based on one hour of instruction. Credit will be available by registering and completing
an evaluation at www.phppo.cdc.gov/ phtnonline.
The course number for this program is WD0075. Credit will be available
through August 2008.
If you need additional help
you may call 800-41-TRAIN or 404-639-1292, Monday through Friday, from 8 am until
4:40 pm Eastern time.
Or, you may write us at
C-E at C-D-C dot G-O-V. [PAUSE]
Now, let’s review the
objectives for this program.
Upon successful completion,
you should be able to identify high-risk and low-risk types of genital HPV infection,
and discuss the epidemiology of genital
HPV infection in the United States.
You should also be able to
describe the natural history of genital HPV infection and identify methods used
to detect cervical cellular abnormalities for the prevention of cervical cancer
....and describe the clinical uses of the HPV DNA tests in the context of Pap
test screening and management.
Finally, you should be
able to summarize appropriate patient counseling messages for genital HPV
infection, and identify methods for preventing genital HPV infection.
At the end of the program,
there will be a question and answer session, at which time the panel will
answer questions that have been previously e-mailed.
We will not be accepting
phone calls.
Dr. Douglas, let’s begin
with you for an introduction to genital HPV infection.
[3]DOUGLAS
Thank you, Kysa.
Genital HPV infection is
very common in sexually active men and women.
It’s estimated that at
least 50 percent of sexually active women are infected with genital HPV
at some point in their lives, and it’s likely that comparable rates would be
found in men ...if there were good HPV testing methods available for
men.
Papillomaviruses are a
complex group of DNA tumor viruses. They are found in many species, where they
can cause benign growths, or papillomas, and cancers. They can’t be routinely grown in the lab.
This makes it hard to test
experimental treatment. Papillomaviruses are most commonly detected by the presence
of DNA.
HPV types are distinguished
by genetic sequences, hence their designation as genotypes. More than 30 genotypes
of HPV are sexually transmitted and can infect the genital tract.
Genital HPV infection is a
sexually transmitted infection, but it’s not transmitted like many other STDs,
which are passed from partner to partner through semen or other bodily fluids.
Instead, it’s transmitted through skin-to-skin contact.
Genital HPV infections are
transmitted primarily by penetrative genital contact, usually through vaginal
or anal sex. But penetration isn’t the only way HPV can be transmitted.
It can also be passed through
oral-genital, manual-genital, and external genital, genital contact, although
we believe these routes of transmission are much less efficient and thus, much
less common than sexual intercourse.
In most cases, genital HPV
infection is transient, asymptomatic, and resolves without treatment or without
a person ever being aware they had the infection.
When clinical manifestations
do occur in adults, they most typically include: genital warts, as shown on
this slide, cellular abnormalities known as intra- epithelial neoplasia, and
anogenital squamous cell cancers.
The most common clinically
significant manifestation of genital HPV infection is cervical intra-epithelial
neoplasia, or CIN, which is detected by Pap test screening.
CIN is generally classified
as low-grade, or CIN1, or high-grade, including CIN 2 or 3. High-grade abnormalities
have some risk of progression to cancer and are thus considered cancer precursors.
Finding and treating these
high-grade lesions through Pap smear screening is the backbone of cervical
cancer prevention programs.
The approximately 30 types
of genital HPV are divided into low-risk and high-risk types based on their association
with cervical cancer.
Low-risk types of genital
HPV can cause genital warts and benign or low-grade cervical cell changes that result
in mild Pap test abnormalities.
These abnormalities are
not associated with cervical cancer.
An estimated 1.4 million
people have genital warts at any one time in the United States. That’s about 1%
of the sexually active population, making genital warts one of our most common
STDs.
Very rarely, genital HPV
infection can also occur in the respiratory tract where wart-like lesions cause
a syndrome known as recurrent respiratory papillomatosis, or RRP. This syndrome
can occur in adults, possibly due to oral-genital sexual contact, but is more common
in young children due to perinatal transmission. In children, estimates of the incidence
rate for RRP are imprecise, but range from 0.4 to 1.1 cases per 100,000
children. Although data are limited, cesarean delivery does not appear to be
protective and is not recommended to prevent RRP in the children of women with
genital warts. The most common low-risk HPV types are types 6 and 11. Other
low-risk types include types 40, 42, 43, 44, 54, 61, 72, 73, and 81.
The vast majority of
genital warts are caused by types 6 and 11.
While all of the low-risk
types can cause low-grade Pap smear abnormalities, .it is important to emphasize
that they are rarely associated with higher-grade cervical cell changes.
Because of this, testing
for low-risk types is not recommended for clinical management.
Infection with high-risk
types of genital HPV can cause both low-grade and high-grade cervical cell
abnormalities.
In rare cases, infection
with high-risk genital HPV that is not cleared by the immune system
– known as persistent
infection
– can cause cancers of the
cervix, vulva, anus, and penis.
Common high-risk types of
genital HPV are 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 82.
HPV 16 is found in approximately
half of all women with cervical cancers. HPV 16 is also the single most commonly
identified HPV type in CIN 2, 3.
Infection with high-risk
types of genital HPV is much more common than infection with low-risk types.
Again, it is important to emphasize
that. In addition, an estimated 5%-30%
of people infected with genital HPV are infected with multiple types of the
virus.
Infection with either low-risk
or high-risk types of genital HPV usually causes no clinical signs or symptoms
and is transient.
As mentioned, genital HPV infections
are primarily transmitted through sexual activity.
And because people infected
with genital HPV typically don’t know that they have the virus, infections are commonly
shared between sex partners.
Certain risk factors are
associated with acquiring a genital HPV infection.
These include being 25
years of age or younger, and having first sexual intercourse at the age of 16
or younger.
The risk of acquiring a
genital HPV infection increases with an increasing number of lifetime sex
partners. In addition, having sex with a new partner may be a stronger risk
factor for acquiring a genital HPV infection than having sex with a steady
partner. Finally, having sex partners who have had multiple sex partners also increases
the risk of infection.
[4]DANIELS
Thank you, Dr. Douglas.
Since genital HPV infections
are so common in the United States,
Dr. Saraiya, what can you
tell us about the epidemiology of genital HPV infection and cervical cancer in
this country?
[5]SARAIYA
Well, Kysa, it’s difficult
to assess incidence and prevalence information on genital HPV infection because
it’s not a reportable infection in any state, although genital warts are
reportable in a few states.
The reason for this is
that most genital HPV infections are brief and symptomatic or sub clinical —
that is, they usually have no visible clinical manifestations or clinical consequences.
Given the high prevalence of infection, case reporting would be burdensome for providers,
health departments, and laboratories while at the same time providing no
personal or public health benefit.
However, as already mentioned,
infection with genital HPV is believed to be extremely common.
CDC estimates that 15% of
the population
--or about 20 million people
--currently have a detectable
genital HPV infection, and an estimated 9.2 million sexually active adolescents
and young adults 15 to 24 years of age are infected with genital HPV.
An estimated 6.2 million
new genital HPV infections occur each year.
It is important to emphasize
that only a small percentage of women infected with genital HPV develop
persistent infections.
And only women who develop
these persistent infections are at risk for developing high-grade cancer precursors
and cancers.
The most critical risk factor
for developing cervical cancer is not participating in a routine cervical cancer
screening program.
Other risk factors that
may increase the chance of developing cervical cancer precursors and cervical
cancers include:
-- Cigarette smoking which
has been consistently shown to be an independent risk factor
-- Less consistent, but A
few well-designed studies have also shown that long-term use of oral contraceptives
and having a high number of live births is also a risk factor.
And co-infection with
Chlamydia trachomatis or herpes simplex virus type 2 may be considered cofactors
along with HPV
Cervical cancer once
claimed the lives of more American women than any other type of cancer.
But over the last 40
years, widespread cervical cancer screening using the Pap test and treatment of
precancerous cervical abnormalities has resulted in
a marked reduction in the
incidence of and mortality due to cervical cancer in the
United States.
Incidence of new cervical
cancer cases has fallen by approximately 75% since the introduction of Pap
screening programs.
This slide here using cancer
registry data shows how both new cases and deaths from cervical cancer have
dropped approximately 30 to 40 percent over the last
25 years.
According to the American
Cancer Society, there will be 10,370 new cases of cervical cancer and 3,710
deaths from the disease in 2005.
But there are disparities
in both incidence and mortality in cervical cancer among certain racial and
ethnic subgroups.
For example, using data
from CDC’s National Program of Cancer Registries and
NCI’s SEER Cancer Registries,
we see that incidence rates for cervical cancer among black women is about 1.5
times that in white women.
Similarly, rates for
Hispanic women are 1.5 times higher than that of non-Hispanic women and,
although not shown on this slide, incidence for certain Asian subgroups, such
as Vietnamese women, are much higher than other Asian subgroups.
In general, women born
outside the United States have higher mortality rates from cervical cancer than
U.S. born women.
This map shows that even
in the U.S., there are some regional disparities.
The red areas indicate the
higher mortality rates.
As you can see, the
Appalachian states, states in the south, and states bordering Mexico have
higher mortality rates from cervical cancer.
At least some of these
variations are explained by differences in socioeconomic indicators such as income,
education, possibly cultural barriers, and access to screening.
Usually we think in terms
of predisposing factors which contribute to cervical cancer incidence for
example,
- HPV,
- sexual activity at an
early age,
- multiple sexual partners,
and
- smoking), .but we’ve now
identified that the most serious factor contributing to cervical cancer incidence
and mortality is lack of screening.
This pie chart highlights
experience with cervical cancer screening among women who actually develop cervical
cancer.
While there are a variety
of factors contributing to failure of the prevention program, such as; false
negative cytology tests and inadequate follow up, by far the largest factor is
lack of screening.
Up to 60% of cervical cancer
cases in the United States occur among women who have never been screened or rarely
been screened.
Even when it comes to Pap
testing in the U.S., there are some women who are less likely to have had a
recent Pap. Data from a 2000 national health interview survey shows that,
overall, 83 percent of women reported a Pap in the last 3 years —but the data
also showed considerably lower screening rates among
- women without health
insurance,
- recent immigrant women,
and
- women of Hispanic or
Asian origin.
[6]DANIELS
Thank you, Dr. Saraiya.
Now, for the natural history
of genital HPV infection, let’s go to Dr. Wright.
[7]WRIGHT
Thanks, Kysa.
As we’ve stated, most
genital HPV infections are asymptomatic or sub clinical, and are transient.
They have no clinical consequences in immunocompetent individuals.
The interval between first
exposure and clinical signs is unclear, but it’s probably three weeks to one
year for genital warts.
Most genital HPV infections
clear spontaneously within 1-2 years.
HPV 16 is more likely to
persist than other HPV types, but in most cases, even with HPV 16, infection
becomes undetectable within two years.
The gradual development of
an effective immune response is thought to be the likely mechanism for HPV DNA
clearance.
Currently it is unclear whether
those genital HPV infections that become non-detectable using standard
molecular tests have completely cleared or whether they remain latent in basal
cells with the potential for later reactivation.
If the virus is able to
remain in a nondetectable dormant state and reactivate
many years later, it may
explain why some older women in a mutually monogamous relationship can begin to
shed genital HPV.
It’s also important to
note that HPV is more likely to be detected in people who are immunosuppressed,.such
as those who are HIV-infected, have had an organ transplant, or are undergoing chemotherapy.
An HPV infection that
persists is required for high-grade cervical cancer precursors and invasive
cervical cancers to develop.
A persistent infection is
an infection that is not cleared by the immune system and is characterized by persistently
detectable HPV DNA.
Factors associated with
persistent infection include being 30 years of age and older, having high-risk
HPV types, and having a suppressed immune system.
However, it’s important to
note that most women with persistent HPV infection do not develop precancerous cervical
cell changes or cervical cancer.
[8]DANIELS
What do clinicians need to
know about cervical cancer screening and current recommendations, Dr. Saraiya?
[9]SARAIYA
Cervical cell abnormalities
are frequently attributed to the transient presence of certain HPV types. These
abnormalities usually have no signs or symptoms, and they often regress spontaneously
without either detection or treatment.
When cervical cell abnormalities
are detected, it’s
usually by cervical cytology —the Pap test. Cervical cytology is used as a
screening tool to identify women who need a diagnostic biopsy. Characteristic changes
in the cells shed and scraped from the surface are predictive of underlying
changes.
Histological evaluation,
on the other hand, requires a full thickness biopsy or excision.
Biopsies are usually obtained
while visualizing lesions with colposcopy—a magnified examination of the cervix.
Biopsies are considered
the “gold standard” and key to diagnosis of cervical cell abnormalities.
Here is a slide that shows
the difference between histology and cytology.
The Pap test does not
directly detect HPV. It detects -
epithelial cell changes that are frequently due to genital HPV infection.
If they are not detected,
these changes may lead to cervical cancer.
There are two Pap
test methods - the conventional Pap test and the newer liquid-based cytology or
LBC. Each has pros and cons.
In a conventional Pap
test, cells are scraped from the cervix and placed on a slide to be examined in
a laboratory.
The sensitivity of a
single conventional cytology test is between 51% and 88%, although the sensitivity
increases with repeated testing as is currently recommended.
The specificity of a single
conventional cytology test is between 95% and 98%.
False negatives in
conventional Pap tests can occur for a number of reasons:
- samples may not contain
enough cervical cells,
- abnormal cells may be
hard to see because of inflammation or mucus,
- or a lab technician may
simply not see abnormal cells.
For LBC, cells are
suspended in liquid medium and then applied to a slide in a laboratory as a
thin cellular layer, eliminating most blood, mucus, and inflammatory cells. There
has been a lot of controversy about the comparative sensitivities and specificities
of the 2 approaches, largely due to a lack of well-designed studies.
The Liquid based Pap has a
higher sensitivity but lower specificity. The evidence based on sensitivity and
specificity of conventional Pap vs. liquid-based cytology does not indicate
that LBC should be the standard.
There are other factors,
though, that might make LBC more attractive. Because only a portion of the LBC sample is
used in preparing the slide for cytologic examination, residual material can be
used for HPV DNA testing when very mild cytological abnormalities are found
which are referred to as ASC-US.
Conventional cytology
requires the collection of a separate sample at the time of the cervical swab
or a return visit by the patient for collection of a new sample.
More satisfactory results
have been reported with LBC, in part because the technique reduces problems
with preparation of the sample.
The disadvantage of LBC
tests is that they are more expensive than conventional cytology.
The 2001 Bethesda System
is a modification of the previous one from the 1990's for classifying PAP test
results. I’ll be focusing today on
squamous cell abnormalities in the Bethesda system, which differs from the
older classification system in that it subdivides atypical squamous cells, or
ASC, that don’t appear to be completely normal into two categories.
The first is atypical squamous
cells of undetermined significance, or ASC-US.
ASC–US changes are usually
mild or equivocal abnormalities, and are sometimes related to genital HPV
infection.
These are quite common in
the United States. Approximately 4%-5% of all cervical cytology results are reported
as ASC-US.
The second is ASC–H, or atypical
squamous cells that cannot exclude a high-grade squamous intraepithelial
lesion, or HSIL.
ASC–H changes are more
likely to be precancerous abnormalities.
A separate category is
low-grade squamous intraepithelial lesion, or LSIL, which are generally cellular
changes due to a transient infection with a
high-risk HPV type. This
encompasses HPV, mild dysplasia, and CIN 1.
The last category is
high-grade squamous intraepithelial lesion, or HSIL--generally cellular changes
due to a persistent infection with a high-risk HPV type with a higher risk for progression
to cervical cancer.
This encompasses: moderate
and severe dysplasia, CIN 2, CIN 3 and
CIS.
This slide shows us just
how common these Pap test abnormalities are.
It is estimated that of
the 50 million Pap tests that are performed every year, approximately
-- 2 million are ASC-US Paps,
these include a small proportion that are ASC-H,
-- 1 million are LSIL Paps, and
-- 300,000 HSIL Paps.
In addition to these new Bethesda
Classifications, several organizations provide guidelines for cervical cancer screening,
including:
- the age to begin screening,
- screening intervals, and
- special
considerations.
These organizations include
the American Cancer Society (ACS), the American College of Obstetricians and
Gynecologists ACOG), and the U.S. Preventive Services Task Force (USPSTF).
These organizations have
agreed on several things in the last decade, in particular the age to start
screening, and who not to screen.
However, there are some differences.
They also differ in how often to screen, and on the use of HPV testing in cervical
cancer screening.
All 3 organizations suggest
that cytologic screening begin within three years of onset of sexual
intercourse or age 21, whichever comes first, and that women be screened at
least every three years.
However, the ACS recommends
that screening be conducted yearly with conventional Pap tests and biennially
with liquid-based cytology methods up until age 30.
ACOG recommends yearly
screening up until age 30, regardless of the Pap test type used.
According to the ACS and
ACOG, regardless of the Pap test women at or older than age 30 who have had 3 consecutive,
technically satisfactory normal/negative cytology results may be screened every
two to three years.
Of course, women who have
a history of in-utero DES exposure, are HIV positive, or are immuno-
compromised. These women may require
more frequent screening.
As to when to stop screening,
the USPSTF and ACS recommends against routinely screening women older than 65
to 70 respectively if they have had adequate recent screening with normal Pap
smears and are not otherwise at high risk for cervical cancer.
ACOG states that it is
difficult to set an upper age limit, and that it should be determined on an individual
basis, based on medical history and risk factors for CIN.
The USPSTF, ACOG, and ACS
recommend against routine Pap smear screening in women who have had a total hysterectomy
for benign disease. A molecular test to detect
HPV DNA has been approved by the FDA.
This test, known as
solution hybridization, detects most of the high-risk types and several of the more
common low-risk types of HPV.
The FDA approved the
high-risk HPV DNA test to be used in basically 2 ways:
-- For management of women
with ASC-US Pap tests in the context of screening.
-- HPV DNA testing may be
added to cervical cytology for screening in women 30 years of age and older.
This has been called adjunct
screening, primary screening, or HPV with PAP test screening.
Tom will provide more
detail on this later.
As you can see in this
slide, several organizations have followed with recommendations on the use of
the HPV test for both ASC-US triage and for HPV testing with the Pap test for routine
cervical cancer screening. Although the USPSTF did not address HPV testing for
management of abnormal Pap tests, USPSTF found insufficient evidence for
primary screening.
The American Cancer
Society stated that HPV testing along with the Pap test for routine cervical cancer
screening is an option.
The American College of Obstetricians
and Gynecologists recommends — as does the American Society of Colposcopy and Cervical
Pathology —HPV testing for both indications.
[10]DANIELS
Thanks, Dr. Saraiya. Dr.
Wright, can you provide more detail in the role that
HPV DNA testing plays in
cervical cancer screening and management of abnormal Pap tests?
[11]WRIGHT
With the recent FDA
approval of HPV DNA testing as an adjunct to the Pap test to screen for cervical
cancer in women 30 years or older, this approach is beginning to be used by
some clinicians. Both the American Cancer
Society and the American College of Obstetricians and Gynecologists consider
this to be an acceptable approach to screening women 30 years and older.
Recently ACS, NCI, and ASCCP
published guidance to help in the management of specific test results when HPV testing
is used as an adjunct:
Women who are negative by
both HPV DNA testing and cytology, which should be the majority of women, should
not be rescreened before three years. This is because their risk of developing CIN
is quite low.
Women who are cytology
negative but HPV DNA positive should not undergo colposcopy.
Instead HPV DNA testing
along with cervical cytology should be repeated at 6-12 months.
Finally, women who has a
LSIL or greater PAP test should be referred to colposcopy, irrespective of
their HPV result.
Use of the combination of
HPV DNA testing and cervical cytology should be discontinued at the same age,
and under the same circumstances, as discontinuance of cervical cytology screening.
However, because 5%-15% of
women age 30 and older will be high-risk
HPV DNA positive, concern
has been raised about the potential negative impacts of using HPV DNA testing
for screening.
These concerns are related
to lack of counseling of women with respect to their risk of cervical disease,
the source of their infection, and their infectivity.
There is also fear that
HPV DNA positive women without CIN 2, 3 or cancer will undergo unnecessarily intensive
and expensive follow-up or treatment.
It needs to be stressed
that HPV DNA testing with the Pap test is not approved as a screening method for
women under age 30.
This is because there’s a
very high rate of transient HPV infection in this age group.
In adolescents and young
adults in their 20’s, the prevalence of high-risk HPV DNA positivity is high, while
the prevalence of cancer is relatively low.
HPV DNA testing is also
not recommended for use in women who are immuno- suppressed for any reason including
infection with HIV. This is because testing
has no proven role in clinical management.
The other way in which HPV
DNA testing is widely used in the United States is to determine which women
with very mild cytological abnormalities,
referred to as ASCUS, require additional workup. As already mentioned, ASCUS results are quite
common, about 5% of all Pap tests.
The 2001 Consensus Guidelines
identify three approaches to managing women with ASCUS.
These include:
-- repeating the Pap test
twice at 4-6 month intervals,
-- performing immediate colposcopy,
or
-- testing for high-risk
HPV DNA.
HPV DNA testing identifies
those women with ASCUS who are at greatest risk for having a high-grade
cervical cancer precursor and who need colposcopy.
In contrast, women with
ASCUS who are HPV DNA negative can simply be followed-up with a repeat cytology
in one year.
It needs to be pointed out
that HPV DNA testing is not indicated in a number of situations. These include women
or men diagnosed with external genital warts, for women or men as a general screening
test for HPV.
HPV testing is also not
indicated for women with LSIL, HSIL, or ASC-H Pap test results.
Testing is not recommended
in those situations because there is no evidence that it improves clinical management.
And for men, HPV DNA test reliability
is not well defined.
[12]DANIELS
Dr. Wright, how should
providers counsel and educate their patients about genital HPV infection?
[13]WRIGHT
Kysa, the general U.S.
population has very limited knowledge about genital HPV infection and its
relationship with cervical cancer. Nonetheless, studies have found a high level
of anxiety and concern among women when informed that they are infected with genital
HPV.
Patient counseling and
education about HPV should take place
-- when genital warts are
diagnosed,
-- at Pap screening
visits,
-- when a Pap test result
is abnormal, and
-- when a HPV test is
positive.
Counseling should include:
- general information about
HPV infection,
- how HPV infection is
transmitted,
- how to prevent HPV
infection and its clinical manifestations, and.
- partner issues.
Counseling may be assisted
by the use of written materials.
The general information
about genital HPV infection that patients need to know starts with the fact that
most sexually active adults will become infected with genital HPV at some point
in their lives, and the infection usually goes away.
Patients need to know that
the interval between time of infection and onset of signs or symptoms is
variable, and it is often difficult to determine the source of infection.
They also need to know
that there are two types of genital HPV.
Low-risk genital HPV types
that are associated with mild Pap test abnormalities and genital warts and
high-risk types that can be associated with high-grade cancer precursor lesions
as well as cancers of the cervix, vulva, anus, and penis.
When counseling patients, it
needs to be stressed that persistent infection over many years with a high-risk
genital HPV type is necessary but is not sufficient for the development of
cervical cancer.
The vast majority of women
infected with low-risk or high-risk HPV types will not develop significant
cervical cancer precursors and will never develop cervical cancer.
As for how genital HPV
infections are transmitted, patients need to know that it’s usually difficult
to determine the source of infection, and that infection is not evidence of infidelity.
Moreover, the likelihood
of transmission and duration of infectivity with or without treatment cannot be
predicted in an individual patient.
Strategies to prevent genital
HPV infection include:
- abstinence from sexual
activity,
- mutual monogamy with an
uninfected partner,
- limiting the number of
sex partners, and
- using condoms.
Having said this, the most
important thing sexually active women can do to avoid getting cervical cancer
is to have regular cervical cancer screening.
With respect to partner
issues, the key counseling points are:
First, patients need to know
that genital HPV is commonly transmitted between sex partners, making it likely
that partners are already infected once an HPV infection is detected.
Second, the value of disclosing
a past diagnosis of genital HPV infection to future partners is unclear,
although candid discussions about past STDs should be supported whenever possible.
And finally, sex partners
of patients diagnosed with genital warts may benefit from an examination to
assess for the presence of genital warts and other STDs.
[14]DANIELS
Thank you, Dr. Wright.
Dr. Douglas, can you
elaborate on preventing the transmission of genital HPV infections?
[15]DOUGLAS
Sure, Kysa.
In general, strategies to
prevent transmission of sexually transmitted infections include:
-- reducing the duration
of infectiousness by treatment,
-- decreasing the
efficiency of transmission by measures aimed at reducing infectivity, and
-- reducing the number of
sex partners.
First, regarding
treatment, currently there is no effective systemic treatment for genital HPV
infection.
Genital warts are treated
with topical pharmacologic agents.
Cervical cancer precursors
are treated with local measures such as cryotherapy, electrocautery, or
surgical excision.
Evidence indicates that currently
available therapies for HPV-related cervical cell abnormalities and genital
warts may reduce infectiousness, but probably don’t eliminate it.
Second, the most common approach
to decreasing the efficiency of transmission of a STD is to use a physical barrier
such as a condom.
However, because genital
HPV infections are transmitted through skin-to-skin contact, and because infections
can occur in male and female genital areas that are not covered by a latex
condom as well as those areas that are covered, condoms can’t offer complete protection
from genital HPV infection.
Because of inadequate
existing scientific studies, just how effective condoms are in preventing
genital HPV infection is unknown and thus they cannot be relied upon as a
primary strategy for prevention of these infections.
However, condoms have been
associated with lower rates of genital warts and cervical cancer.
Third, the most effective way
to avoid acquiring genital HPV infection is to limit the number and type of sex
partners.
The surest way to prevent
future genital HPV infection is to abstain from any genital contact, including
non-penetrative intimate contact of the genital area.
For those who choose to be
sexually active, long-term mutual monogamy with a single uninfected partner is
likely to be the next most effective way to prevent infection.
However, as we discussed,
it is difficult to determine whether a partner who has been sexually active in
the past is currently infected with HPV because there is no general screening
test for HPV —and most infected people are asymptomatic and have no clinical manifestations
of infection.
For people who are sexually
active who are not in a long-term mutually monogamous relationship, reducing
the number of sex partners and choosing a partner who is less likely to be
infected with genital HPV —meaning a partner with no or few previous sex partners
—may reduce the risk of acquiring genital HPV infection.
Finally, the most
important thing sexually active women can do to avoid getting cervical cancer
is to have regular cervical cancer screening with the Pap test and
follow up as recommended.
[16]DANIELS
Dr. Douglas, is there a
vaccine for genital HPV infections?
[17]DOUGLAS
Not currently, Kysa.
However, several potential
HPV vaccine approaches are under investigation.
These vaccines use viral-like
particles (VLPs), which preserve native conformation of viral proteins but are
non-infectious because they lack viral DNA.
In a recent double-blind,
multi-center randomized clinical trial, administration of an HPV type 16 VLP vaccine
was highly effective in preventing persistent HPV 16 infection and also
HPV-16-related CIN.
Likewise, a study of a combined
HPV 16-18 vaccine was also highly effective in preventing persistent infections
and abnormal Pap smears caused by both types.
In the future, receiving a
safe and effective HPV vaccine to help prevent genital HPV infection as well as
the HPV-associated diseases of genital warts and cervical cancer may be an
important prevention measure.
However, because vaccines are
unlikely to provide 100% protection and because they likely will not include
all types of genital HPV, an effective HPV vaccine would not replace
other prevention strategies such as reduced sexual exposure and regular Pap
tests.
[18]DANIELS
In closing, Dr. Douglas, what
are the bottom line key messages about genital HPV infection that clinicians
should convey to their patients?
[19]DOUGLAS
Well Kysa, there a number
of messages that clinicians should convey to their patients.
First, HPV infection is
common in sexually active adults.
Second, most HPV
infections are transient and have no signs or symptoms.
Third, persistent
infection with a high-risk HPV type is necessary but not sufficient for the development
of cervical cancer.
And last, cervical cancer
is by far the most important problem caused by genital HPV infection.
The most important tool to
prevent it is regular Pap test screening and follow-up for all sexually active women.
[20]DANIELS
Doctors,
thank you for bringing us up to date on preventing and treating genital human papillomavirus
infection and cervical cancer.
Now we’ll move on to the
question and answer segment of our program.
Please be reminded that
these questions were submitted via email prior to this webcast by you, our
viewing audience.
(Q & A 10 minutes
not scripted)
[21]DANIELS
Thank you, doctors. That
ends our question and answer period.
And, thank you for your
attention during this Webcast. We have attempted to provide you with an update
on prevention strategies for genital HPV infections and cervical cancer.
We hope that this presentation
will help clinicians understand, diagnose,
and manage genital HPV
infections.
I’d like to thank our panelists...Doctors
John Douglas, Mona Saraiya, and
Tom Wright.
This brings us to the
close of “Human Papillomavirus (HPV) and Cervical Cancer: An Update on Prevention
Strategies.”
I’m Kysa Daniels and it
has been my pleasure to be your moderator today.
Good-bye.
*******************