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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

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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


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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


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GENITAL HPV INFECTION1% 1.4 MILLION VISIBLE WARTS4% 5 MILLION Subclinical (Colposcopy)10% 14 MILLION Subclinical (DNA testing)60% 81 MILLION Prior infection (+ antibodies)25% 34 MILLION No prior/current infection


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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


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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


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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.


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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


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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


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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


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Genital Warts in a Male

Source: CDC/ NCHSTP/ Division of STD Prevention,

STD Clinical Slides

Source: Cincinnati STD/HIV Prevention Training Center


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HPV Penile Warts

Source: Cincinnati STD/HIV Prevention Training Center



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Intra-meatal Wart of the Penis(and Gonorrhea)

Source: Florida STD/HIV Prevention Training Center


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Circumcision and HPV

  • Risk for penile cancer

  • May influence the risk of HPV acquisition, transmission and cervical cancer


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Female Genital Warts

Source: CDC/NCHSTP/Division of STD, STD Clinical Slides


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HPV Warts on the Thigh

Source: Cincinnati STD/HIV Prevention Training Center


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Perianal Warts

Source: Cincinnati STD/HIV Prevention Training Center


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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)


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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.


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HPV Diagnostic Techniques

  • History

  • Visual exam

  • Pap smears

  • DNA testing


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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


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HPV Treatment Options

  • Chemical agents

  • Cryotherapy

  • Electrosurgery

  • Surgical excision

  • Laser surgery

  • Imiquimod (Aldara)

  • Defer treatment

  • Natural therapies


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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


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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%


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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


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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?


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HPV is INCURABLE

Warts can and often do recur after treatment.

Virus can remain in surrounding tissue after warts have been destroyed.



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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



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PapillomavirusTreatment 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


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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



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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.


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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


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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


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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 persistentinfections 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


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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)

Cofactors for Cervical Cancer

LACK OF SCREENING IS THE MOST IMPORTANT FACTOR


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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?


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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


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Pap Smears2001 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)


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Pap Smears2001 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


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Pap Smears2001 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


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Pap Smear Terms

  • Cervical Dysplasia

  • Abnormal cell changes

  • Precancerous cell changes

  • CIN (Cervical Intraepithelial Neoplasia)

  • SIL (Squamous Intraepithelial Lesions)

  • “Warts” on the cervix


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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


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Abnormal pap tests

  • What is usually recommended?

    • Re-testing

    • Treat with antibiotics

    • HPV-DNA testing

    • Colposcopy

    • Biopsy


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Why can’t men be tested for HPV?

  • Studies have been unable to standardize specificity and sensitivity in men leading to clinical ambiguity


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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?


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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.


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When Is an HPV Test Used? an HPV test?

  • 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


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When Is an HPV Test an HPV test? NOT Used?

  • If the Pap result shows dysplasia or pre-cancerous changes

  • In women under age 30

  • Not on males


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HPV an HPV test? 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.


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Non-detectable HPV an HPV test?

  • 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


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Treatment for Cervical Dysplasia an HPV test?

  • Cryotherapy

  • LEEP

  • Conization

  • Laser

  • No treatment but regular repeat testing


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Key Educational Messages an HPV test?

  • 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


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Pregnancy and an HPV test? Cervical Dysplasia

  • For some, cervical dysplasia may increase

  • Monitor cervix closely

  • Rarely treat during pregnancy


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HPV Vaccine an HPV test?


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Gardasil an HPV test?

  • 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


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How well does Gardasil work? an HPV test?

  • 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


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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


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Can males use Gardasil? HPV?

  • 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


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How is Gardasil administered? HPV?

  • 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)


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Potential adverse reactions HPV?

  • 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.


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How long does the vaccine protection last? HPV?

  • 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)


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Other Vaccines in Development HPV?

  • 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


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Important Notes HPV?

  • 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


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HPV Prevention HPV?

  • 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.


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HPV Resources and Support HPV?

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


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Additional information HPV?

  • 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


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