_papillomavirus人乳头瘤病毒（ppt74）课件

Human Papillomavirus (HPV) Genital Warts Human Papillomavirus (commonly called Genital Warts) lHuman Papillomavirus (HPV) is a virus that can cause various disease states including “genital” or “venereal” warts lPapillomaviruses are a complex group of DNA tumor viruses. They can cause benign growths (papillomas), cancers, or more commonly, transient infections lHPV 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 lMost common STD Yearly incidence of 6.2 million 20 million currently infected 80 million infected at least once between the ages of 15-49 lAn estimated 9.2 million sexually active adolescents and young adults 15-24 years of age are infected with genital HPV lAn estimated 5%-30% of people infected with genital HPV are infected with multiple types of the virus l316,000 initial visits to physicians offices (2004)-genital wart diagnosis GENITAL HPV INFECTION 1% 1.4 MILLIONVISIBLE WARTS 4% 5 MILLIONSubclinical (Colposcopy) 10% 14 MILLIONSubclinical (DNA testing) 60% 81 MILLION Prior infection (+ antibodies) 25% 34 MILLIONNo prior/current infection Epidemiology of HPV and Cervical Cancer lOver 99% of cervical cancers have HPV DNA detected within the tumor l70% of cervical cancer is caused by one of two types of HPV, 16 or 18 lThe quadrivalent HPV vaccine protects against Types 6, 11, 16 and 18 Risk Factors for Acquiring a Genital HPV Infection lYoung age (less than 25 years) lMultiple sex partners lEarly age at first intercourse (16 years or younger) lMale partner has (or has had) multiple sex partners HPV Transmission lDirect skin-to-skin contact Usually, but not always sexual contact lInfected birth canal lFomites (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? lIt can occur in the mouth, throat or respiratory tract lIt is relatively uncommon lIt appears to be an inefficient mode for transmission HPV Incubation lAverage incubation is 3 weeks to 1 year lPossibly years before appearance of warts or cervical abnormalities lSome will be transient and may never be detected Common Symptoms of Genital Warts in Males lCan be treated by removing the warts; lThe virus cannot be removed, so the warts may grow back. HPV Diagnostic Techniques lHistory lVisual exam lPap smears lDNA testing Papillomavirus Treatment lPrimary goal for treatment of visible warts is the removal of symptomatic warts lTherapy may reduce but probably does not eradicate infectivity lDifficult to determine if treatment reduces transmission No laboratory marker of infectivity Variable results utilizing viral DNA HPV Treatment Options lChemical agents lCryotherapy lElectrosurgery lSurgical excision lLaser surgery lImiquimod (Aldara) lDefer treatment lNatural therapies Papillomavirus lSurgical removal lPatient-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 lProvider-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 lTherapy choice needs to be guided by preference of patient, experience of provider, and patient resources (time and/or money) lNo evidence exists to indicate that any one regimen is superior lAn 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 lNo link with premature labor, miscarriage, or other complications lLow rate of transmission to baby lRange is generally from 0.4 to 1.1 cases/100,000 births lC-section is not recommended in most instances Treatment Regimens Papillomavirus Treatment in Pregnancy lImiquimod, podophyllin, and podofilox should not be used in pregnancy lMany specialists advocate wart removal due to possible proliferation and friability lHPV types 6 and 11 can cause respiratory papillomatosis in infants and children lPreventative 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 lThose who develop warts will usually do so within several weeks lFirst-born child lJuvenile 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 lCervical 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 lSingle 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 lAssociated with cancer of the penis, anus, vagina and vulva. HPV DNA Classification lLow Risk HPV Types: 6,11,40,42,43,44, 54, 61, 72, 73, 81 types 6 and 11 responsible for 95% of visible warts lHigh-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? lThere 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. lThe risk for re-infection with that specific type of HPV appears to be rare. lHowever, a person can be infected with more than one type of HPV HPV and Cervical Cancer lInfection is generally indicated by the detection of HPV DNA lRoutine Pap smear screening ensures early detection (and treatment) of pre-cancerous lesions lOnly 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 lActive/passive Cigarette Smoking lChronic inflammation associated with other STDs lLong term use of oral contraceptives lHigh number of live births* lWeakened immune system lMultiple sex partners lSex at an early age lNutritional deficiencies lMother who took DES lLack of circumcision of male partner(s) LACK OF SCREENING IS THE MOST IMPORTANT FACTOR Pap Smears lWhat is it? lHow is it done? lWhen should I get the first one? lHow often do I need one? lDo I still need to get one if Ive been vaccinated? Preparing for a Pap Smear lSchedule a day when you wont be having your period lDo not douche 48 hours before the test lAvoid sexual intercourse 48 hours before the test lDo not use tampons, vaginal creams, foams, films or other jellies for 48 hours before the test Pap Smears 2001 Bethesda System lSpecimen type Coventional vs Liquid sample lSpecimen adequacy Satisfactory or unsatisfactory for evaluation lGeneral categorization Negative for Intraepithelial lesion/malignancy Epithelial cell abnormality (squamous or glandluar) Other things observed (ex. Endometrial cells) Pap Smears 2001 Bethesda System lEpithelial cell abnormalities Squamous lAtypical squamous cell of undetermined significance(ASC-US) lCannot exclude HSIL (ASC-H) lLow-grade squamous intraepithelial lesion (LSIL) Includes HPV/mild dysplasia/CIN 1 lHigh-grade squamous intraepithelial lesion (HSIL) Includes moderate, severe dysplasia, CIS/CIN 2 and 3 lSquamous cell carcinoma Pap Smears 2001 Bethesda System lEpithelial cell abnormalities (continued) Glandular cells lAtypical Endocervical (Not otherwise specified, or favor neoplastic) Glandular (not otherwise specified or favor neoplastic) Endometrial lEndocervical carcinoma in situ lAdenocarcinoma Endocervical Endometrial Extrauterine Not otherwise specified Pap Smear Terms lCervical Dysplasia lAbnormal cell changes lPrecancerous cell changes lCIN (Cervical Intraepithelial Neoplasia) lSIL (Squamous Intraepithelial Lesions) l“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 lWhat is usually recommended? Re-testing Treat with antibiotics HPV-DNA testing Colposcopy Biopsy Why cant men be tested for HPV? lStudies 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? lPap test finds abnormal cell changes on the cervix lBiopsy is when a cluster of cells is removed from the cervix to confirm earlier Pap smear results and rule out cancer lHPV test looks for genetic material (DNA) of HPV within cells. When Is an HPV Test Used? lAs a follow-up test if the Pap result is “borderline” lIn combination with a Pap test in women at the age of 30 and older lFalse positive results can occur When Is an HPV Test NOT Used? lIf the Pap result shows dysplasia or pre -cancerous changes lIn women under age 30 lNot on males HPV Good News l70% 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. lThe gradual development of an effective immune response is thought to be the likely mechanism for HPV DNA clearance. lWomen who develop high risk lesions only have a 5% to 15% chance of developing cancer in the absence of treatment. Non-detectable HPV lCurrently 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 lReactivation may explain why some older women in a mutually monogamous relationship can begin to shed genital HPV lHPV more likely to be detected in persons with immune system disorders Treatment for Cervical Dysplasia lCryotherapy lLEEP lConization lLaser lNo treatment but regular repeat testing Key Educational Messages lHPV infection is very common, few will develop cervical cancer lHPV is not a reliable indicator of a womans sexual behavior or that of her partner lMost HPV infections are transient, harmless, have no signs/symptoms, and are cleared by the immune system lPersistent HPV infection over many years is necessary but not sufficient for the development of cervical cancer lCervical cancer can be prevented by vaccination and early detection-regular Pap smears Pregnancy and Cervical Dysplasia lFor some, cervical dysplasia may increase lMonitor cervix closely lRarely treat during pregnancy HPV Vaccine Gardasil lApproved in June 2006 Produced by Merck and Co. lFirst vaccine to prevent cervical cancer lRecombinant vaccine lApproved for use in females aged 9-26 Ideally, before becoming sexually active lProtects 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? lFour multinational studies were conducted lWomen between ages of 16-26 Given placebo or vaccine l100% 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 lTested with similar results in females aged 9-15 Will Gardasil help a female who already has a vaccine type HPV? lGardasil only works to prevent four HPV types lIt is not a treatment for one or more of the HPV types lHowever, 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? lGardasil 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. lOnce the study is complete, the FDA will review the data and make recommendations How is Gardasil administered? lThree injections given over a six-month period lInitial dose lSecond dose is given 2 months later lThird and last dose is given 4 months after the second dose or six months after the initial dose lIt is administered in the upper arm or thigh (intramuscularly) Potential adverse reactions lMild/moderate pain or tenderness at the injection site lFemales who are allergic to yeast or any component of the vaccine should not receive Gardasil. lIt is not a live vaccine, so it cannot cause an infection with HPV. lThe vaccine is not recommended for pregnant women. lLactating women can receive the HPV vaccine. lImmunocompromised women can receive this vaccine. How long does the vaccine protection last? lVaccine protection is usually not known when a vaccine is first introduced lStudies that have followed w