Human Papillomavirus (HPV)
Genital Warts
Human Papillomavirus
(commonly called Genital Warts)
Human Papillomavirus (HPV) is a virus that
can cause various disease states including
“genital” or “venereal” warts
Papillomaviruses are a complex group of
DNA tumor viruses. They can cause benign
growths (papillomas), cancers, or more
commonly, transient infections
HPV infection is causally associated with
cervical cancer ; other genital cancers
including anal, penile, vulvar, and vaginal
cancers may have HPV as co-factor
HPV Prevalence
Most common STD
– Yearly incidence of 6.2 million
– 20 million currently infected
– 80 million infected at least once between the ages
of 15-49
An estimated 9.2 million sexually active
adolescents and young adults 15-24 years of
age are infected with genital HPV
An estimated 5%-30% of people infected with
genital HPV are infected with multiple types of
the virus
316,000 initial visits to physicians’ offices
(2004)-genital wart diagnosis
GENITAL HPV INFECTION
1%
4%
10%
60%
25%
1.4 MILLION
5 MILLION
14 MILLION
81 MILLION
34 MILLION
VISIBLE WARTS
Subclinical (Colposcopy)
Subclinical (DNA testing)
Prior infection (+ antibodies)
No prior/current infection
Epidemiology of HPV and
Cervical Cancer
Over 99% of cervical cancers have HPV
DNA detected within the tumor
70% of cervical cancer is caused by one
of two types of HPV, 16 or 18
The quadrivalent HPV vaccine protects
against Types 6, 11, 16 and 18
Risk Factors for Acquiring a
Genital HPV Infection
Young age (less than 25 years)
Multiple sex partners
Early age at first intercourse (16 years
or younger)
Male partner has (or has had) multiple
sex partners
HPV Transmission
Direct skin-to-skin contact
– Usually, but not always sexual contact
Infected birth canal
Fomites (very rare)
Friction and abrasion are key factors.
Difficult to determine how and where infection
occurred due to poor standardized tests and
variable latency periods.
What about oral sex?
It can occur in the mouth, throat or
respiratory tract
It is relatively uncommon
It appears to be an inefficient mode for
transmission
HPV Incubation
Average incubation is 3 weeks to 1 year
Possibly years before appearance of warts or
cervical abnormalities
Some will be transient and may never be
detected
Common Symptoms of Genital
Warts in Males & Females
The symptoms may include single or multiple
fleshy growths around the penis, scrotum,
groin, vulva, vagina, anus, and/or urethra
They may also include: itching, bleeding, or
burning, and pain
The symptoms may recur from time to time
Genital Warts in a Male
Source: CDC/ NCHSTP/ Division of STD Prevention,
STD Clinical Slides
Source: Cincinnati STD/HIV Prevention
Training Center
HPV Penile Warts
Source: Cincinnati STD/HIV Prevention Training Center
Pearly Penile Papules
Intra-meatal Wart of the Penis
(and Gonorrhea)
Source: Florida STD/HIV Prevention Training Center
Circumcision and HPV
•Risk for penile cancer
•May influence the risk of HPV
acquisition, transmission and
cervical cancer
Female Genital Warts
Source: CDC/NCHSTP/Division of STD, STD Clinical Slides
HPV Warts on the Thigh
Source: Cincinnati STD/HIV Prevention Training Center
Perianal Warts
Source: Cincinnati STD/HIV Prevention Training Center
Complications of Genital Warts
(if untreated)
It may destroy body tissue around the
genitals and anus
For pregnant women
– Delivery complications or need for C-section
– Juvenile Onset Recurrent Respiratory
Papillomatosis (JO-RRP)
Testing & Treatment for
Genital Warts
Can be detected in a
clinical exam;
Can be treated by
removing the warts;
The virus cannot be
removed, so the
warts may grow
back.
HPV Diagnostic Techniques
History
Visual exam
Pap smears
DNA testing
Papillomavirus
Treatment
Primary goal for treatment of visible warts
is the removal of symptomatic warts
Therapy may reduce but probably does not
eradicate infectivity
Difficult to determine if treatment reduces
transmission
–No laboratory marker of infectivity
–Variable results utilizing viral DNA
HPV Treatment Options
Chemical agents
Cryotherapy
Electrosurgery
Surgical excision
Laser surgery
Imiquimod (Aldara)
Defer treatment
Natural therapies
Papillomavirus
Surgical removal
Patient-applied
Podofilox (Condylox) 0.5% solution or gel
Apply 2x/day for 3 days, followed by 4 days of no therapy.
Repeat as needed, up to 4x
or
Imiquimod (Aldara) 5% cream
Apply 1x/day @ bedtime 3x/week for up to 16 weeks
Provider-administered
Cryotherapy (liquid nitrogen) *repeat every 1-2 weeks
or
Podophyllin resin 10-25% *thoroughly wash off in 1-4 hrs
or
Trichloroacetic or
Bichloroacetic acid 80-90%
*can be repeated weekly
Papillomavirus
Vaginal warts
Cryotherapy or TCA/BCA 80-90%
Urethral meatal warts
Cryotherapy or podophyllin 10-25%
Anal warts
Cryotherapy or TCA/BCA 80-90%
Papillomavirus
Therapy choice needs to be guided by
preference of patient, experience of
provider, and patient resources (time
and/or money)
No evidence exists to indicate that any
one regimen is superior
An acceptable alternative may be to do
nothing but watch and wait; possible
regression/uncertain transmission
Case Study
Amy was diagnosed with genital warts and successfully
treated with liquid nitrogen therapy three years ago. The
genital warts have never returned after therapy.
Amy has met someone new and she wants to begin a
sexual relationship. She wants to know if she needs to
disclose her prior infection to her new partner.
What would you tell Amy?
HPV
is
INCURABLE
Warts can and often do recur after treatment.
Virus can remain in surrounding tissue after
warts have been destroyed.
Perinatal complications
HPV and Pregnancy
No link with premature labor,
miscarriage, or other complications
Low rate of transmission to baby
Range is generally from 0.4 to 1.1
cases/100,000 births
C-section is not recommended in
most instances
Treatment Regimens
Papillomavirus
Treatment in Pregnancy
Imiquimod, podophyllin, and podofilox should not
be used in pregnancy
Many specialists advocate wart removal due to
possible proliferation and friability
HPV types 6 and 11 can cause respiratory
papillomatosis in infants and children
Preventative value of cesarean section is
unknown; may be indicated for pelvic outlet
obstruction or if vaginal delivery would result in
excessive bleeding
HPV in Neonates
Those who develop warts will usually do
so within several weeks
First-born child
Juvenile onset recurrent respiratory
papillomatosis (JO-RRP)
– rare -- 1 per 100,000 births
– types 6 and 11
– occurs up to age four
HPV and Cervical Cancer
HPV Linked to Cancer
Cervical Cancer
–
–
–
–
10,000 new cases diagnosed/year in the US
3,000 deaths/year in the US
400,000-500,000 new cases internationally
300,000 deaths/year internationally, especially in
developing countries
Single most important factor for cervical cancer
– Virtually all squamous cell cervical cancer contain one
of 18 types of HPV
– The type of HPV that causes visible warts are not
linked to cervical cancer
Associated with cancer of the penis, anus, vagina
and vulva.
HPV DNA Classification
Low Risk HPV Types: 6,11,40,42,43,44, 54,
61, 72, 73, 81
– types 6 and 11 responsible for 95% of visible warts
High-Risk HPV Types: 31,33,35,39,45, 51,
52, 56, 58, 59, 68,82
High cancer risk: 16
– Most common-50% of cervical cancer
High cancer risk: 18
– 10-12% of cervical cancer
*Risk not well established yet: 26, 53, 66, 73
Can a person be
re-infected with HPV?
There appears to be humoral and probably
cellular immunity that develops to a specific type
of HPV after a person has been infected with it
and “has cleared” it.
The risk for re-infection with that specific type of
HPV appears to be rare.
However, a person can be infected with more
than one type of HPV
HPV and Cervical Cancer
Infection is generally indicated by the
detection of HPV DNA
Routine Pap smear screening ensures early
detection (and treatment) of pre-cancerous
lesions
Only a small percentage of women infected
with genital HPV develop persistent infections
– Only women who develop persistent infections
are at risk for developing high-grade
pre-cancerous changes / cervical cancer
– Most women with persistent HPV infection do NOT
develop precancerous changes/cervical cancer
– The most critical factor for developing cervical
cancer is not having routine pap smears
Cofactors for Cervical Cancer
Active/passive
Cigarette Smoking
Chronic inflammation
associated with other
STDs
Long term use of oral
contraceptives
High number of live
births*
Weakened immune
system
Multiple sex partners
Sex at an early age
Nutritional deficiencies
Mother who took DES
Lack of circumcision of
male partner(s)
LACK OF SCREENING IS THE MOST IMPORTANT FACTOR
Pap Smears
What is it?
How is it done?
When should I get the first one?
How often do I need one?
Do I still need to get one if I’ve been
vaccinated?
Preparing for a Pap Smear
Schedule a day when you won’t be having
your period
Do not douche 48 hours before the test
Avoid sexual intercourse 48 hours before
the test
Do not use tampons, vaginal creams,
foams, films or other jellies for 48 hours
before the test
Pap Smears
2001 Bethesda System
Specimen type
– Coventional vs Liquid sample
Specimen adequacy
– Satisfactory or unsatisfactory for evaluation
General categorization
– Negative for Intraepithelial lesion/malignancy
– Epithelial cell abnormality (squamous or
glandluar)
– Other things observed (ex. Endometrial cells)
Pap Smears
2001 Bethesda System
Epithelial cell abnormalities
– Squamous
Atypical squamous cell of undetermined
significance(ASC-US)
Cannot exclude HSIL (ASC-H)
Low-grade squamous intraepithelial lesion (LSIL)
– Includes HPV/mild dysplasia/CIN 1
High-grade squamous intraepithelial lesion (HSIL)
– Includes moderate, severe dysplasia, CIS/CIN 2 and 3
Squamous cell carcinoma
Pap Smears
2001 Bethesda System
Epithelial cell abnormalities (continued)
– Glandular cells
Atypical
– Endocervical (Not otherwise specified, or favor neoplastic)
– Glandular (not otherwise specified or favor neoplastic)
– Endometrial
Endocervical carcinoma in situ
Adenocarcinoma
–
–
–
–
Endocervical
Endometrial
Extrauterine
Not otherwise specified
Pap Smear Terms
Cervical Dysplasia
Abnormal cell changes
Precancerous cell changes
CIN (Cervical Intraepithelial Neoplasia)
SIL (Squamous Intraepithelial Lesions)
“Warts” on the cervix
Interpreting Pap smears
Interpretation of Pap smears can be difficult:
– Abnormalities may not be picked up by
the spatula or brush
– Abnormalities may be difficult to see
Abnormal pap tests
What is usually recommended?
– Re-testing
– Treat with antibiotics
– HPV-DNA testing
– Colposcopy
– Biopsy
Why can’t men be tested
for HPV?
Studies have been unable to standardize
specificity and sensitivity in men leading to
clinical ambiguity
Case Study
Laura and Shane have dated throughout High
School. They love and care for each other very
much. One evening, Laura told Shane that she
had an abnormal Pap smear and may have HPV.
•What should Shane do to see if he has HPV?
•How can Shane protect himself from getting
HPV?
What is the difference between
the Pap test, a biopsy and
an HPV test?
Pap test finds abnormal cell changes on the
cervix
Biopsy is when a cluster of cells is removed
from the cervix to confirm earlier Pap smear
results and rule out cancer
HPV test looks for genetic material (DNA) of
HPV within cells.
When Is an HPV Test Used?
As a follow-up test if the Pap result is
“borderline”
In combination with a Pap test in women
at the age of 30 and older
False positive results can occur
When Is an HPV Test
NOT Used?
If the Pap result shows dysplasia or
pre-cancerous changes
In women under age 30
Not on males
HPV
Good News
70% of new HPV infections spontaneously clear
within one year, and as many as 91% clear
within 2 years. The median duration of new
infections is typically 8 months.
The gradual development of an effective
immune response is thought to be the likely
mechanism for HPV DNA clearance.
Women who develop high risk lesions only have
a 5% to 15% chance of developing cancer in the
absence of treatment.
Non-detectable HPV
Currently it is unclear whether 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
Reactivation may explain why some older
women in a mutually monogamous relationship
can begin to shed genital HPV
HPV more likely to be detected in persons with
immune system disorders
Treatment for Cervical
Dysplasia
Cryotherapy
LEEP
Conization
Laser
No treatment but regular repeat
testing
Key Educational Messages
HPV infection is very common, few will
develop cervical cancer
HPV is not a reliable indicator of a woman’s
sexual behavior or that of her partner
Most HPV infections are transient, harmless,
have no signs/symptoms, and are cleared by
the immune system
Persistent HPV infection over many years is
necessary but not sufficient for the
development of cervical cancer
Cervical cancer can be prevented by
vaccination and early detection-regular Pap
smears
Pregnancy and
Cervical Dysplasia
For some, cervical dysplasia may increase
Monitor cervix closely
Rarely treat during pregnancy
HPV Vaccine
Gardasil
Approved in June 2006
– Produced by Merck and Co.
First vaccine to prevent cervical cancer
Recombinant vaccine
Approved for use in females aged 9-26
– Ideally, before becoming sexually active
Protects against infection with
Types 6, 11, 16, 18
– Women aren’t protected if they have already been
infected with the HPV type(s) that are covered by the
vaccine prior to vaccination
How well does Gardasil work?
Four multinational studies were conducted
Women between ages of 16-26
– Given placebo or vaccine
100% effective in preventing precancerous
cervical, vaginal, and vulvar lesions and genital
warts in women not already infected with the
types of HPV found in the vaccine
Tested with similar results in females aged 9-15
Will Gardasil help a female who
already has a vaccine type HPV?
Gardasil only works to prevent four HPV
types
It is not a treatment for one or more of the
HPV types
However, females already infected with
one or more of the four types of HPV can
still receive protection from the vaccine
HPV type(s) she has not acquired
Can males use Gardasil?
Gardasil has not been approved for use in
males, but the manufacturer currently has
a study underway to see if it is safe and
effective for men.
Once the study is complete, the FDA will
review the data and make
recommendations
How is Gardasil administered?
Three injections given over a six-month
period
Initial dose
Second dose is given 2 months later
Third and last dose is given 4 months after
the second dose or six months after the
initial dose
It is administered in the upper arm or thigh
(intramuscularly)
Potential adverse reactions
Mild/moderate pain or tenderness at the
injection site
Females who are allergic to yeast or any
component of the vaccine should not receive
Gardasil.
It is not a live vaccine, so it cannot cause an
infection with HPV.
The vaccine is not recommended for pregnant
women.
Lactating women can receive the HPV vaccine.
Immunocompromised women can receive this
vaccine.
How long does the vaccine
protection last?
Vaccine protection is usually not known when a
vaccine is first introduced
Studies that have followed women for 5 years
indicate they are still fully protected
More research is being done to see if a booster
will be needed years later
It is not yet known how much protection would
be given with only one or two vaccines (of the
three)
Other Vaccines in Development
GSK has a bivalent vaccine (Cervarix) that
is still in research studies
They have sought FDA approval; it is
anticipated to be approved in December
2007 or early 2008
It would protect against Types 16 and 18
Important Notes
Women should continue to receive regular
cervical cancer screening (pap smears)
– The vaccine will NOT protect against all types of
genital HPV
– Women may not have completed the full series of
vaccinations
– If they had been exposed to one or more types prior
to vaccination, there is still a risk for cervical
abnormalities and/or genital warts to develop
Women should continue to practice protective
sexual behaviors since the vaccine will not
prevent all cases of genital HPV or other STDs,
including HIV
HPV Prevention
Abstinence
Monogamy
Condoms
Removal of warts
Vaccine (Females aged 9-26)
50% to 70% of sex partners of people
with genital warts already have or do
develop warts.
HPV Resources and Support
HPV Hotline 1-877-HPV-5868
(ASHA publications “HPV News”)
(919) 361-8422
CDC Hotline 1-800-227-8922
TDH STD/HIV Info-line
(800) 299-AIDS
Additional information
Centers for Disease Control and Prevention
(CDC)
– www.cdc.gov/std/hpv
American Social Health Association (ASHA)
– www.ashastd.org
National Cancer Institute
– 1-800-CANCER (422-6237)
– www.cancernet.nci.nih.gov