Human Papillomavirus and HIV-Infected Women November 2007 This slide set was developed by members of the Cervical Cancer Screening Subgroup of the AETC Women's Health and Wellness Workgroup: Laura Armas, MD; Texas/Oklahoma AETC Susa Coffey, MD; AETC National Resource Center Abigail Davis, MS, ANP, WHNP; Mountain Plains AETC Rebecca Fry, MSN, APN; François-Xavier Bagnoud Center Jamie Steiger, MPH; AETC National Resource Center Other subgroup members and contributors include: Lori DeLorenzo, MSN, RN; Organizational Ideas Karen A. Forgash, BA; AETC National Resource Center Kathy Hendricks, RN, MSN; François-Xavier Bagnoud Center Supriya Modey, MBBS, MPH; AETC National Resource Center Andrea Norberg, MS, RN; AETC National Resource Center Peter Oates, RN, MSN, ACRN, NP-C; François-Xavier Bagnoud Center Pamela Rothpletz-Puglia, EdD, RD; François-Xavier Bagnoud Center Jacki Witt, JD, MSN, WHNP; Clinical Training Center for Family Planning 2 Learning Objectives 1. Define what human papillomavirus (HPV) is and how it is transmitted 2. Explain the relationship between HPV, genital warts, and cervical cancer 3. Describe the health risks associated with HIVHPV coinfection 4. Discuss screening for HPV and management of women with HIV and HPV 5. Describe cultural competency issues related to providing care for women with HPV-HIV coinfection 3 General HPV Infection DNA virus Spread by direct skin-to-skin contact, usually vaginal or anal sex Approximately 50% of sexually active population infected during lifetime Credit: Stephen C. Harrison, PhD 70% of infections cleared by immune system within 1 year Over 100 types of HPV Infection usually asymptomatic Requires monitoring by Pap smear and HPV DNA testing (women over 30 or abnormal Pap smear) 4 Types of HPV Oncogenic strains can lead to cancer of the cervix, vulva, or anus (16, 18, 31, 33, 39, 45, 51, 52, 56, 58, 59, 68, 82 ) Types 16 and 18 account for most cases of cervical cancers in women Types 6 and 11 most commonly cause genital warts Analysis of 932 specimens from women in 22 countries indicated prevalence of HPV DNA in cervical cancers worldwide = 99.7% 5 Epidemiology of HPV Prevalence of HPV among women ages 14-59 in the United States was 26.8% Prevalence of HPV among HIV-infected women may be upwards of 60% 6 Normal Anatomy 7 Credit: Netter image reused with the permission of Elsevier Inc. Anal Warts Credit: STI AIDS Netherlands Credit: Seattle STD/HIV Prevention Training Center, University of Washington 8 Vaginal & Perineal Warts Credit: STI AIDS Netherlands 9 Molluscum Contagiosum and Herpes Simplex Virus Credit: www.dermnet.com Credit: Jean R. Anderson, MD Reprinted from BC Medical Journal, December 2004; 46(10):512 10 Treatment of Genital Warts Treatment directed at HPV-associated lesions Local removal (cryotherapy, electrocautery, laser therapy, surgical excision) Topical application with various pharmacological agents (Podofilox 0.5%, Imiquimod 5%, podophyllin resin 10-25%) Removal of lesions probably reduces, but does not eliminate infectiousness 11 Cervical Warts Must rule out high-grade SIL in all women who have cervical warts Usually visualized during colposcopy (not Pap smear) Management of cervical warts should be done in consultation with a specialist 12 HPV-HIV Coinfection HIV-infected women have higher rates of HPV infection when compared with HIV uninfected women with similar risk factors WIHS HERS HIV-infected women are more likely to be infected with multiple subtypes of HPV Multiple sub-type infections increase rates of SIL Credit: www.dermnet.com 13 HPV-HIV Coinfection (continued) HIV-infected women have (a): Compromised immune systems and experience common infections such as HPV Higher prevalence of HPV More persistent forms of HPV Higher risk of being infected with more than one type of HPV Higher rates of abnormal Pap smears Higher incidence of cervical cancer 14 HPV and Immunosuppression Inverse relationship between measures of immunity and HPV for HIV-infected women As CD4 cell count drops (and viral load increases), prevalence of HPV infection increase Studies show a higher rate of oncogenic HPV infections in women with lower CD4 cell counts Role of antiretroviral (ARV) therapy, immune reconstitution, and HPV Jury still out… ARV therapy (so far) has not been shown to 15 prevent progression of dysplasia Screening for HPV in HIV-Infected Women A Papanicolaou or Pap test is used to screen for cervical abnormalities due to HPV infection Two types of tests are Conventional cytology: detects dysplasia, but cannot be used to test for HPV DNA Liquid cytology: detects dysplasia and allows for reflex HPV DNA testing for high and low risk types Initial Pap test performed when first diagnosed with HIV or when first present for care Repeat test 6 months later After two consecutive “normal” results, an HIV-infected woman should have a Pap smear annually 16 Grading Pap Smear Results (Cervical cytology) Normal Negative for intraepithelial lesion or malignancy ASC-US Atypical squamous cells of undetermined significance ASC-H Atypical squamous cells – cannot exclude HSIL LSIL Low-grade squamous intraepithelial lesion HSIL High-grade squamous intraepithelial lesion AGUS Other – atypical glandular cells of undetermined significant SCC Squamous cell carcinoma 17 Management of Abnormal Pap Results in HIV-infected Women Credit: Permission granted from original source Screen women using liquid cytology Normal Repeat in 6 months. After two consecutive normal results, screen annually. ASC-US – ASC-US 3 Options See next slide cannot exclude HSIL Refer for colposcopy LSIL or HSIL Refer for colposcopy Atypical glandular cells of undetermined significance Refer for colposcopy 18 Management of ASC-US in HIV-infected Women ASC-US Option 1: Perform HPV DNA testing Option 2: Repeat Pap Smear Option 3: Refer for colposcopy 19 Role of HPV-DNA Testing In managing an abnormal result (ASC-US): In performing routine screening for cervical cancer as an adjunct to Pap smear: NYS AIDS Institute – no role for HPV-DNA testing American Society for Colposcopy and Cervical Pathology (ASSCP) – used to triage ASC-US result American College of Obstetricians and Gynecologists (ACOG) – used to triage ASC-US result American Cancer Society (ACS) – approved for routine use in women > 30 years ACOG -approved for routine use in women > 30 years USPSTF – insufficient evidence to recommend for or against 20 HIV and the HPV vaccine HPV vaccine (Gardasil®) Protects against the four types of HPV that cause the most cases of cervical cancer and genital warts (16, 18, 6, 11) Vaccine was well studied and appears to be safe, effective, and does not appear to cause any serious side effects HPV vaccine has not been tested on HIV-infected women or girls “The presence of immunosuppression, like that experienced in patients with HIV infection, is not a contraindication to the quadrivalent HPV vaccine. However, the immune response may be smaller in the immunocompromised patient than in immunocompetent patients.” -ACOG 21 HPV Infection and Detection by Anal Pap Smears HIV-infected men and women are at higher risk of developing squamous cell cancer of the anus (especially MSM) It is possible that screening HIV-infected patients with anal Pap smears will decrease the morbidity and mortality associated with anal cancers and dysplasia Evidence in support of performing routine anal Pap smears not available…yet, but some guidelines recommend anal Pap tests at baseline and annually for: MSM Any patient with history of anogenital warts 22 Women with abnormal cervical or vulvar histology Providing Culturally Competent Care The following factors can influence a woman’s understanding of HPV, cervical cancer, and need for regular screening: Language and literacy level Cultural and social background and it’s impact on her understanding of health, illness, and the female anatomy Comfort with discussing sexual health issues Comfort and previous experience with pelvic exams and Pap smears Ability to follow-up with colposcopy 23 Cultural Competency Discussion Incidence cervical cancer for black women is 1.5 times higher than that for white women Incidence for Hispanic women also higher than that for white women Death rates for black women were twice those for white women What are the clinical care implications for HIV-infected women of color based on this epidemiological information? 24 Pearls of Wisdom Genital warts typically indicate infection with low-risk types of HPV in uninfected women, but HIV-infected women can be infected with more than one type of HPV Healthcare workers may want to use liquid-based cytology for a Pap smear with a reflex for HPV-DNA testing to avoid having to repeat exams if the results of the Pap smear are abnormal HIV-infected women who are symptomatic or have low CD4 cell counts may be candidates for more frequent Pap screenings (ie, more than annually) 25 Conclusions HPV infections are more common, more virulent, and more persistent in HIV-infected women Pap smears are the standard of care in HIV-infected women for screening for cervical abnormalities that accompany HPV infection Pap smears should be performed upon diagnosis with HIV and then 6 months later If both are normal, repeat Pap smears annually For HIV-infected women with abnormal Pap results, HPV-DNA can be a useful tool to help triage women for colposcopy In most clinical situations, women with abnormal Pap results (ASC-US or above) will need colposcopy as soon as possible with close follow-up of results 26 Helpful Resources AETC National Resource Center (NRC), www.aidsetc.org Clinical Manual for Management of the HIV-Infected Adult Health Resources and Services Administration HIV/AIDS Bureau, http://hab.hrsa.gov/ A Guide to the Clinical Care of Women with HIV/AIDS Centers for Disease Control and Prevention, http://www.cdc.gov/std/hpv/default.htm Human Papillomavirus: HPV Information for Clinicians STD Treatment Guidelines 2006 AIDSMAP, http://www.aidsmap.com/cms1032598.asp American Society for Colposcopy and Cervical Pathology, http://www.asccp.org/hpv.shtml#provider Association of Reproductive Health Professionals, http://www.arhp.org/healthcareproviders/cme/webcme/index.cfm HIVInsite, http://hivinsite.ucsf.edu/InSite?page=kb-00&doc=kb-06-04-01 Planned Parenthood, http://www.plannedparenthood.org/sexual-health/std/hpv.htm 27 References Ahdieh, L., Klein, R.S., Burk, R., Cu-Uvin, S., Schuman, P., Duerr, A., Safaeian, M., Astemborski, J., Daniel, R., Shah, K., (2001). Prevalence, incidence, and type-specific persistence of human papillomavirus in human immunodeficiency virus (HIV)-positive and HIV-negative women. Journal of Infectious Diseases, 184:68290. AIDSMAP, Treatment and Care, Human papilloma virus. Retrieved on September 12, 2007 from http://www.aidsmap.com/cms1032598.asp AIDSMAP, Treatment and Care, Molluscum contagiosum. Retrieved on September 12, 2007 from http://www.aidsmap.com/cms1032608.asp Anderson, J.R, ed. (2005). A Guide to the Clinical Care of Women with HIV. Health Resources and Services Administration HIV/AIDS Bureau. Ault, K.A. (2006). Epidemiology and Natural History of Human Papillomavirus Infections in the Female Genital Tract. Infectious Diseases in Obstetrics and Gynecology, Vol. 2006: 40470. Bhatia, A., Forman, S., Rowe, D., Orenstein, R., & Nunley, J.R. Molluscum Contagiosum. Retrieved on September 12, 2007 from http://www.emedicine.com/MED/topic1491.htm#section~author_information Bleeker, M.C., Hogewoning, C.J., Voorhorst, F.J., van den Brule, A.J., Snijders, P.J., Starink, T.M., Berkhof, J., & Meijer, C.J. (2003). Condom use promotes regression of human papillomavirus-associated penile lesions in male sexual partners of women with cervical intraepithelial neoplasia. International Journal of Cancer, 107(5):804-10. Centers for Disease Control and Prevention. Human Papillomavirus: HPV Information for Clinicians. Retrieved on September 12, 2007 from http://www.cdc.gov/std/hpv/hpv-clinicians-brochure.htm Centers for Disease Control and Prevention, Quadrivalent Human Papillomavirus Vaccine. MMWR, March 12, 2007, 56. Centers for Disease Control and Prevention. Sexually Transmitted Diseases Treatment Guidelines 2006. Retrieved on September 12, 2007 from http://www.cdc.gov/std/treatment/2006/genital-warts.htm 28 References Centers for Disease Control and Prevention, Sexually Transmitted Infections, Human Papillomavirus Infection. Retrieved on September 11, 2007 from http://www.cdc.gov/std/hpv/default.htm Chiao, E.Y., Giordano, T.P., Palefsky, J.M., Tyring, S., El Serag, H. (2006) Screening HIV-infected individuals for anal cancer precursor lesions: a systematic review. Clinical Infectious Disease, 15;43(2):223-33 Dunne, E.F., Unger, E.R., Sternberg, M., McQuillan, G., Swan, D.C., Patel, S.S., & Markowitz, L.E. (2007). Prevalence of HPV infection among females in the United States. Journal of the American Medical Association, 297(8):813-9. Gardner, E.I.O., (2003). Cervical Cancer: Disparities in Screening, Treatment, and Survival. Cancer Epidemiology, Biomarkers & Prevention, 12: 242s-247s Haas, S., Park, T.W., Voigt, E., Buttner, R., Merkelbach-Bruse, S. (2005). Detection of HPV 52, 58 and 87 in cervicovaginal intraepithelial lesions of HIV infected women. International Journal of Molecular Medicine, 16: 815-9. Health Resources and Services Administation, HIV/AIDS Bureau, AETC National Resource Center. (2006). Guiding Principles for Cultural Competency. Retrieved on September 18, 2007 from http://www.aidsetc.org/doc/workgroups/cc-principles.doc Klevens, R.M., Fleming, P.L., Mays, M.A., & Frey, R. (1996). Characteristics of women with AIDS and invasive cervical cancer. Obstetrics and Gynecology, 88 (2),: 269-73. Lomalisa, P., Smith, T., & Guidozzi, F. (2000). Human immunodeficiency virus infection and invasive cervical cancer in South Africa. Gynecological Oncology, 77 (3):460-3. Luque, A.E., Demeter, L.M., & Reichman, R.C. (1999). Association of human papillomavirus infection and disease with magnitude of human immunodeficiency virus type 1 (HIV-1) RNA plasma level among women with HIV-1 infection. Journal of Infectious Diseases, 179: 1405–1409. Maiman, M., Fruchter, R.G., Serur, E., Remy, J.C., Feuer, G., & Boyce, J. (1990). Human immunodeficiency virus infection and cervical neoplasia. Gynecological Oncology, 38: 377–382. Minkoff, H., Feldman, J., DeHovitz, J., Landesman, S., & Burk, R. (1998). A longitudinal study of human papillomavirus carriage in human immunodeficiency virus-infected and human immunodeficiency virusuninfected women. American Journal of Obstetrics & Gynecology, 178: 982–986. 29 References New York State Department of Health AIDS Institute. (2007) Human Papillomavirus (HPV). Retrieved November 12, 2007 from http://www.hivguidelines.org/Content.aspx Our Bodies, Ourselves Health Resource Center, Sexual Anatomy, Reproduction, and the Menstrual Cycle. Retrieved on September 11, 2007 from http://www.ourbodiesourselves.org/book/companion.asp?id=13&compID=37 Palefsky, J.M., Minkoff, H., Kalish, L.A., Levine, A., Sacks, H.S., Garcia, P., Young, M., Melnick, S., Miotti, P., & Burk, R. (1999). Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)positive and high risk HIV-negative women. Journal of the National Cancer Institute, 91: 226–236. Strick, L.B., Wald, A., & Celum, C. (2006). Management of herpes simplex virus type 2 infection in HIV type 1infected persons. Clinical Infectious Diseases, 43(3):347-56. Strickler, H.D., Palefsky, J.M., Shad, K.V., Anastos, K., Klein, R.S., Minkoff, H., Duerr, A., Massad, L.S., Celentano, D.D., Hall, C., Fazzari, M., Cu-Uvin, S., Bacon, M., Schuman, P., Levine, A.M., Durante, A..J., Gange, S., Melnick, S., & Burk, R.D. (2003). Human papillomavirus type 16 and immune status in human immunodeficiency virus-seropositive women. Journal of the National Cancer Institute, 95(14):1062-71. The Well Project, Human Papilloma Virus. Retrieved on September 12, 2007 from http://www.thewellproject.org/en_US/Diseases_and_Conditions/Other_Diseases_and_Conditions/HPV.jsp;jsessionid =FByKYh78pYlCJZRlzRgnPvjSfBFggxglnyy7x2bXcyHRLfpJmnd9!-44492584 Walboomers, J.M., Jacobs, M.V., Manos, M.M., Bosch, F.X., Kummer, J.A., Shah, K.V., Snijders, P.J., Peto, J., Meijer, C.J., & Munoz, N. (1999). Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. Journal of Pathology, 189 (1):1-3. Wright, T.C., Massad, L.S., Dunton, C.J., Spitzer, M., Wilkinson, E.J., & Solomon, D. (2007). 2006 Consensus guidelines for the management of women with abnormal cervical cancer screening tests. American Journal of Obstetrics & Gynecology,197(4):337-9. 30