In 1993, the Centers for Disease Control (CDC) added cervical neoplasia (cervical cancer) to the list of AIDS-defining illnesses. The incidence of cervical, anal, vulvar, and vaginal human papillomavirus (HPV) disease is 5-10% greater in individuals infected with HIV than in those not infected with HIV. 1-6 HPV is the primary etiologic cause of cervical cancer. 7-9

Human papillomavirus disease is the most common viral infection that is sexually transmitted. 8,9 While it is primarily transmitted through anal or vaginal intercourse, approximately 10% of women having sex with women (WSW) have abnormal pap smears.10 HPV is a constellation of more than 100 subtypes that express themselves differently in the human body ranging from benign to cancerous (oncogenic) lesions.8,9,11 Benign HPV lesions can be found on all areas of the genitals, appearing like cauliflower growths. The cancerous subtypes are found primarily on the cervix and are also found on the labial, vaginal, and anal tissue.

HPV infection in women with HIV infection is generally more persistent, consisting of more HPV subtypes (including oncogenic), and is more progressive than in women not infected with HIV.12,13 Immunosuppression from HIV disease, especially with elevating HIV viral loads, may escalate HPV infection; also, HPV may enhance HIV. However, the synergy between HPV and HIV is not clearly understood.1,14 Other opportunistic infections have been reduced by antiretroviral therapy (ART); however ART does not appear to reduce HPV infection.15,16

Progression of HPV infection seems dependent upon some combination of conditions.3,6,17

*    Immunosuppression from HIV disease

*    Having both HIV1 and HIV2 infections

*    HPV viral load

*    Genetic makeup

Factors that contribute to the transmission of HPV are also poorly understood; they include the following6,18,20-23:

*    Inflammation from other viruses and STDs

*    Smoking

*    Age-related physiological factors

*    Unsafe sex, especially with multiple partners

*    Nutritional factors

Condom (male or female) use can significantly reduce the risk of acquiring HPV initially or prevent the acquisition of new HPV subtypes. Condoms will not protect against the HPV viral shedding that is increased with HIV infection and that may contribute to cervical and vaginal lesions. Microbicides and human papillomavirus vaccines are currently in early clinical trials and offer future hope for the reduction and prevention of HPV transmission.

Pap smears remain the most effective screening tool for HPV disease, which often has no symptoms.24 The CDC recommends initial pap smear testing every 6 months for women who are HIV-infected. After receiving two normal pap smears within the first year of screening, individuals with no risk factors for HPV and who have never had an abnormal pap smear can go to annual screening. Anal pap smears are also recommended (1) when anal lesions are found, for men and women at risk for HPV infection transmitted via anal intercourse, and (2) in the presence of cervical disease.2,3 The CDC (1998) recommends that individuals co-infected with HPV (shown by a positive pap smear) and HIV infection should have further evaluation for cervical cancer/disease by colposcopy and directed biopsy.18,19,29 A biopsy is more specific and accurate than a pap smear for understanding the exact stage of HPV. (See Table)

Latent HPV infections or the absence of a lesion with the presence of HPV DNA are more common in HIV-infected individuals. This is commonly seen when a pap smear result of LSIL (low squamous intraepithelial lesion or low grade cervical disease) changes to benign. In HIV-infected women, a benign pap smear generally does not mean the HPV infection has regressed, but only that the HPV viral load has temporarily decreased, a circumstance that indicates latent disease. It is not uncommon over time for normal pap smears to change to high-grade HPV disease in HIV-infected women. Pap screening should continue every 6 months if an HIV-infected individual has ever had an abnormal pap smear.

Evaluation of cervical disease is the same for both HIV-infected and -uninfected women with the exception of ASCUS (atypical squamous cells of undetermined significance) pap smears. ASCUS pap findings have been found to have a high correlation to HPV disease in HIV-infected women and therefore warrant a more aggressive approach (colposcopy with biopsy) to determine the exact stage of cervical disease.25-28 Repeating pap smears is not sensitive enough to screen for high-grade cervical disease that is reported as ASCUS due to insufficient cells.6,24,25,29

 Persons living with HPV should keep a balanced perspective and remain positive. Get treatment and information about the treatment; establish a positive relationship with your healthcare provider; practice safer sex and educate your partners; and practice self careÑthat is, maintain a healthy lifestyle, seek emotional support, eat a healthy diet, get plenty of sleep and exercise, and quit smoking.31,32

Most individuals with an abnormal pap smear or HPV have a range of emotional stresses. Anxiety about having cancer, mood changes, lack of sleep, social isolation and sexual problems, and decreased self-esteem that includes shame, blame, and guilt can be common.32-37 Your ability to practice self-care, to access care, and to adhere to treatment can be is significantly compromised by these factors.

HIV-positive women with cervical, anal, and vulvar HPV disease require GYN examinations that may be embarrassing and uncomfortable year after year. Persons already experiencing depression or posttraumatic stress disorder (especially from sexual abuse) may find GYN exams difficult. Establishing a trusting and respectful relationship with a healthcare provider will make possible the exploration of sensitive subjects related to HPV.31,33,38,39

Pamela J Dole, EdD, MPH, FNP, ACRN is an Assistant Professor at the Hunter-Bellevue School of Nursing, Hunter College, NY, NY. She has a faculty practice in HIV Women's Health Care at St Vincent's Health Center, also in New York City. She is the author of numerous related articles. She holds HIV certification from The Association of Nurses in AIDS Care [ANAC] and is on their Board of Directors. As part of her dedication to incarcerated women, Dr. Dole recently completed the Women's HIV Videotape Initiative for incarcerated women in collaboration with Albany Medical Center. Dr Dole is also recognized as aTherapeutic Touch Mentor, Teacher, and Practitioner by the Nurse Healers Professional Association Inc., and provides holistic care to clients.

References

     1.    TV, Chiasson MA, Bush TJ, Sun XW, Sawo D, Brudney K, Wright TC. Incidence of cervical squamous intraepithelial lesions in HIV-infected women. JAMA. 2000;283(8):.

     2.   Hillemanns P, Ellerbrock TV, McPhillips S, Dole P, et al. Prevalence of anal human papillomavirus infection and anal cytology abnormalities in HIV-seropositive women. AIDS. 1996;10(14):.

     3.   Palefsky J. Anal cancer in HIV infection. International AIDS SocietyÑUSA. 2000;8(7):14-17.

     4.   Chiasson MA, Ellerbrock TV, Bush TJ, et al. Increased prevalence of vulvovaginal condylomata and vulvar intraepithelial neoplasia in women infected with the Human Immunodeficiency Virus. Obstet Gynecol. 1997;89(5):.

     5.   Xiao-wei Sun, Kuhn L, Ellerbrock TV, Chiasson MA, et al. Human papillomavirus infection in women with the Human Immunodeficiency Virus. New Engl J Med. 1997;337(19):.

     6.   Jay N, Moscicki AB. Human papillomavirus infections in women with HIV disease: prevalence, risk, and management. The AIDS Reader. 2000;10(11):.

     7.   Ebrahim SH, Peterman TA, Zaidi AA, Kamb ML. Mortality related to sexually transmitted diseases in US women. Am J Public Health. 1997;87(6):.

     8.   Richart RM. Genital warts: the clinical challenge. Medical Economics, Fall Supplement, 2000. (editor ).

     9.   Wallboomers JM, Jacobs MV, Manos MN, et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999;189:12-19.

     10. Marrazzo JM, Koutsky LA, Kiviat NB et al. Papanicolaou test screening and prevalence of genital human papillomavirus among women who have sex with women. Am J Public Health. 2001;91(6):.

     11. Ho GYF, Bierman R, Beardsley L, Chang CJ, Burk RD. Natural History of cervicovaginal papilloma infection in young women. New Engl J Med. 1998;338:.

     12. Nakagawa M, Stites D, Patel S, et al. Persistence of human papillomavirus 16 infections is associated with lack of cytotoxic T lymphocyte response to the E6 antigen. J Infectious Dis. 2000;182:.

     13. Scott M, Stites DP, Moscicki AB. Th 1 cytokine patterns in cervical HPV. Clinical Diagnostic Laboratory. 1999;6:.

     14. Martinez-Maza O, et al. Human papillomavirus infection facilitates HIV-1 gene expression. Obstet Gynecol. 2000;96:.

     15. Heard I. 8th Annual Retrovirus Conference. Chicago, Il. February 4-8, 2001. [Abstract 518]

     16. WIHS Study. 8th Annual Retrovirus Conference. Chicago, Il. February 4-8, 2001. [Abstract 722]

     17. Langley CL, Benga-De E, Crtichlow CW, et al. HIV-1, HIV-2 and cervical neoplasia in high-risk African women. AIDS. 1996;10:.

     18. Centers for Disease Control. Sexually transmitted diseases treatment guidelines 2002. MMWR. 2002;51(RR-6):1-84.

     19. Anderson, Jean R. Guide to the Clinical Care of Women with HIV. US Department of Health and Human Services, Rockland, MD, 2001. Free manual available at: <http://www.hab.hrsa.gov/>

     20. Childers JM, Chu J, Voight LF, et al. Chemoprevention of cervical cancer with folic acid: a Phase III southwest oncology group intergroup study. Cancer Epidemiol. 1995;4:.

     21. Butterworth CE, Hatch KD, Macalusa M, et al. Folate deficiency and cervical dysplasia. JAMA. 1992;276:.

     22. Palan PR, Mikhail M, Basu J, Romnay SL. Plasma levels of antioxidant B-carotene levels in women with uterine cervical dysplasia and cancer. Nutrition and Cancer. 1991;15(1):13-20.

     23. Vermund SH. Genital human papillomavirus infection. In: Cotton, D, ed. The Medical Management of AIDS in Women. Wiley-Liss, Inc., 1997; pp. .

     24. Wright TC, Ellerbrock TV, Chiasson MA, et al. Cervical intraepithelial neoplasia in women infected with Human Immunodeficiency virus: prevalence, risk factors, and validity of Papanicolaou smears. Obstet Gynecol. 1994;84(4):.

     25. Solomon D, Schiffman M, Tarone R. Comparison of three management strategies for patients with atypical squamous cells of undetermined significance: baseline results from a randomized trial.

J National Cancer Inst. 2001;93(4):293-99.

     26. Wright TC, Moscarelli RD, Dole P, Ellerbrock TC, Chiasson MA, Vandervanter N. Significance of mild cytologic atypia with women infected with human immunodeficiency virus. Obstet Gynecol. 1996;87(4):.

     27. Holcomb K, Abulafia O, Mathews RP, et al. The significance of ASCUS cytology in HIV-positive women. Gynecol Oncol. 1999;75:.

     28. Massad LS, Schneider M, Watts H, Darragh T, Abulafia O, Salzer E, et al. Correlating Papanicolaou smear, colposcopic impression, and biopsy: results from the women's interagency HIV study. J Lower Genital Tract Dis. 2001;5(4):.

29. Holcomb K, Matthews RP, Chapman JE, et al. The efficacy of cervical conization in the treatment of cervical intraepithelial neoplasia in HIV-seropositive women. Gynecol Oncol. 1999;74:.

     30. Centers of Disease Control. NCI Bethesda System 2001. Available at: <http://bethsda2001.cancer.gov>

     31. Taylor CA, Keller ML, Egan JJ. Advice from affected persons about living with human papillomavirus infection. Image: Journal of Nursing Scholarship. 1997;29(1):27-32.

     32. Albany Medical Center. Listen to your bodyÑknowledge is power. HIV Inmate Adherence Series Educational Videotape Women Tape #2, 2001. Available at: <> or by phoning

     33. Abercrombie PR. Improving adherence to abnormal pap smear follow-up. Journal of Obstetrical, Gynecologic and Neonatal Nursing. 2000;30(1):80-88.

     34. McDonald TW, Neutens JJ, Fischer LM, Jessee D. Impact of cervical intraepithelial neoplasia diagnosis and treatment on self-esteem and body image. Gynecol Oncol. 1989;34:.

     35. Lerman C, Miller SM, Scarborough R, Hanjani P et al. Adverse psychologic consequences of positive cytologic cervical screening. Am J Obstet Gynecol. 1991;165:.

     36. Boag FC, Dillon AM, Catalan J, et al. Assessment of psychiatric morbidity in patients attending a colposcopy clinic situated in a genitourinary medicine clinic. Genitourinary Medicine. 1991;67:.

     37. Bennetts A, Irwig L, Oldenburg B, et al. PEAPS-Q: a questionnaire to measure the psychological effects of having an abnormal pap smear. Psychological Effects of Abnormal Pap Smears Questionnaire. J Clin Epidemiol. 1995;48:.

     38. Leenerts MH. The disconnected self: consequences of abuse in a cohort of low-income white women living with HIV/AIDS. Health Care for Women International. 1999;20:.

     39. Dole PJ Centering: reducing rape trauma syndrome anxiety during a gynecologic examination. Journal of Psychosocial Nursing. 1996;34:32-36.

Additional Resources

          Conley LJ, Bush TJ, Ellerbrock TV, Lennox JL, Wu F, Stickfaden TE, Hart CE, Wright TC. Does HAART have an effect on genital HPV DNA virus load in HIV-infected women? Abstracts of the 14th International Conference on AIDS. Barcelona July 7-12, 2002. [Abstract ThPeB7309] Available at: <http://www.aids2002.com/>

          Duerr A, Anderson J, Paramsothy P, Cu-Uvin S, Klein RS, Schuman P. Atypical squamous cells of undetermined significance (ASCUS) in HIV-infected women and women at risk for HIV infection. Abstracts of the 14th International Conference on AIDS. Barcelona July 7-12, 2002. [Abstract ThPeC7545] Available at: <http://www.aids2002.com/>

          Fine S, Castiglia J, Corales R, et al. Anal PAP smears in HIV+ patients at a community-based clinic. Abstracts of the 14th International Conference on AIDS. Barcelona July 7-12, 2002. [Abstract ThPeC7488] Available <http://www.aids2002.com/>

          Palefsky J, Holly E, Ralston M, Jay N, Berry M, Darragh T. Effect of HAART on incidence of anal intraepithelial neoplasia grade 3 among HIV-positive men who have sex with men. Abstracts of the 14th International Conference on AIDS. Barcelona July 7-12, 2002. [Abstract LbOr21] Available at: <http://www. aids2002.com/>