1、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” wartsPapillomaviruses are a complex group of DNA tumor viruses. They can cause benign growths (p
2、apillomas), cancers, or more commonly, transient infectionsHPV 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 current
3、ly 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
4、 initial visits to physicians offices (2004)-genital wart diagnosis,GENITAL HPV INFECTION 1% 1.4 MILLION VISIBLE WARTS 4% 5 MILLION Subclinical (Colposcopy) 10% 14 MILLION Subclinical (DNA testing) 60% 81 MILLION Prior infection (+ antibodies) 25% 34 MILLION No prior/current infection,Epidemiology o
5、f 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
6、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 fac
7、tors. 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,Averag
8、e incubation is 3 weeks to 1 yearPossibly years before appearance of warts or cervical abnormalitiesSome 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,
9、 vagina, anus, and/or urethraThey may also include: itching, bleeding, or burning, and painThe symptoms may recur from time to time,Genital Warts in a Male,Source: Cincinnati STD/HIV Prevention Training Center,Source: CDC/ NCHSTP/ Division of STD Prevention, STD Clinical Slides,HPV Penile Warts,Sour
10、ce: 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 Gen
11、ital 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 gen
12、itals 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 gro
13、w 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 transmissio
14、n 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% s
15、olution 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 weeksProvider-administered Cryotherapy (liquid nitrogen) *repeat every 1-2 weeks or Podophyllin resin 10-25% *thoroughly wash
16、off in 1-4 hrs or Trichloroacetic or Bichloroacetic acid 80-90% *can be repeated weekly,Papillomavirus,Vaginal wartsCryotherapy or TCA/BCA 80-90% Urethral meatal wartsCryotherapy or podophyllin 10-25% Anal wartsCryotherapy or TCA/BCA 80-90%,Papillomavirus,Therapy choice needs to be guided by prefere
17、nce 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 wa
18、rts 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
19、 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
20、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 t
21、ypes 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 sev
22、eral 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
23、 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 A
24、ssociated 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 wartsHigh-Risk HPV Types: 31,33,35,39,45, 51, 52, 56, 58, 59, 68,82High cancer risk: 16 Most common-50% of cervica
25、l cancerHigh 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.
26、 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 p
27、re-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 precancerou
28、s 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
29、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
30、 to get one if Ive been vaccinated?,Preparing for a Pap Smear,Schedule a day when you wont 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
31、 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 cel
32、ls),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) Incl
33、udes 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
34、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,Interpr
35、eting 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 cant men be tested
36、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 H
37、PV. 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
38、 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 NO
39、T 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 develop
40、ment 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 “
41、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 detect
42、ed 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 womans sexual behavior or
43、 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 det
44、ection-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
45、 in females aged 9-26 Ideally, before becoming sexually active Protects against infection with Types 6, 11, 16, 18 Women arent 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 studie
46、s 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 Garda
47、sil 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
48、 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 inj
49、ections 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 ten
50、derness 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.,
