Approximately 300,000 women in the United States are living with HIV infection.1 Among these women, compared with women who are not HIV infected, the prevalence of infection with human papillomavirus (HPV), some types of which cause cervical cancer, is higher.2 Also, in HIV-infected women, HPV infection is more likely to progress to long-standing HPV infection, and these women are more likely to be infected with the types of HPV that are associated with an increased risk of cervical cancer.2,3
The results of Papanicolaou (Pap) tests performed on HIV-infected women indicate that 20%-40% have cervical cytologic abnormalities.3-7 In fact, even in women whose Pap test findings are normal at baseline, the cytologic abnormalities develop at a higher rate than among HIV-negative women; over 3.0 to 5.5 years, abnormalities develop in 20%-35% of HIV-infected women.8,9 Furthermore, cervical cytologic abnormalities in HIV-infected women, compared with women who are not infected, progress more rapidly to invasive cervical cancer.6 Additionally, among HIV-infected women, the rate of treatment failure is increased, and the rate of survival is decreased.10 In 1993, in response to repeated observations of cervical cancer in HIV-infected women, the Centers for Disease Control and Prevention added invasive cervical cancer to the list of AIDS-defining illnesses.
Women with CD4 counts of less than 200 cells per microliter are at particular risk of HPV infection and abnormal Pap test results.7,11 Although much of the research on cervical cancer in HIV-infected women preceded the advent of highly active antiretroviral therapy, the risk of cervical cancer has not decreased since the introduction of this therapy,12 highlighting the continued importance of cervical cancer screening in this population.
Cervical cancer is preventable through screening; early detection and treatment of preinvasive cervical lesions can prevent their progression to invasive cervical cancer. Since 1995, HIV treatment guidelines issued by the US Public Health Service and the Infectious Diseases Society of America have recommended that all HIV-infected women receive cervical cancer screening (by the use of Pap tests) twice during the year after HIV diagnosis and annually thereafter.13-18
To determine whether cervical cancer screening was being performed as recommended, we assessed the prevalence of Pap screening among HIV-infected women; further, we assessed the factors associated with not receiving the recommended cervical cancer screening.
The Supplement to HIV/AIDS Surveillance project was a cross-sectional interview study of HIV-infected persons aged 18 years and older that was designed to collect additional behavioral surveillance information from persons reported as having HIV infection or AIDS. During 2000-2004, data were collected (methods have been described19) in 18 states.
A convenience sample was recruited by using (1) population-based recruitment of all persons reported as having HIV infection or AIDS in Phoenix and Tucson, AZ; Los Angeles County, CA; Delaware; Kansas; Minneapolis/St. Paul, MN; New Mexico; Edisto Health District, Richland County, and Charleston County, SC; Austin, TX; Houston, TX; and Washington; or (2) facility-based recruitment of all eligible persons seeking treatment at selected health care facilities in Denver, CO; Hartford and New Haven, CT; Jacksonville, Miami, and Tampa, FL; Atlanta, GA; Chicago, IL; Baltimore, MD; Detroit, MI; Jersey City and Paterson, NJ; and Philadelphia, PA. At all sites, persons reported as having AIDS were interviewed. For sites in areas with confidential name-based HIV reporting laws, including Arizona; Denver, CO; Detroit, MI; Florida; Kansas; Minnesota; New Jersey; New Mexico; South Carolina; and Texas, participants living with HIV infection, but not AIDS, were also eligible for recruitment.
Interviews were conducted by trained interviewers, and, at some sites, a monetary incentive of $25 or less was provided to participants. Informed consent was obtained before the interview. The study received institutional review board approval at Centers for Disease Control and Prevention and local levels.
Participants were asked a series of questions regarding demographic and socioeconomic factors, drug use, gynecologic history, sexual behaviors, HIV testing and treatment, and use of medical services. The women were also asked whether they had ever had a pelvic examination, where and when it was most recently performed, and whether a Pap test was done at that time. Those who had not had a Pap test at their most recent pelvic exam were asked whether they had ever had a Pap test, and if so, the month and year that it was performed. The date of interview and the dates of pelvic exam and Pap test were used to calculate whether the participant had a Pap test during the year before the interview.
We limited our analysis to women interviewed from May 2000 through June 2004. We excluded women whose diagnosis had been made less than 1 month before the interview. Additionally, we excluded women whose interview date was missing as we were unable to calculate the key variable of having had a Pap test in the past year. For women who provided a year, but no month, for the date of a pelvic exam or a Pap test, June was assigned as the month. We excluded women for whom the year of their most recent pelvic exam or Pap test was missing. For women whose HIV diagnosis had been made during the year before the interview, we did not distinguish whether their Pap test was performed before or after their HIV diagnosis.
For all statistical analyses, we used SAS version 9.1 (SAS Institute, Cary, NC). We used the Cochran-Armitage procedure to test for linear trend, by age group, in the proportion of women without a Pap test. We used χ2 analysis to test for differences in the characteristics of those who did and those who did not receive a Pap test and to calculate unadjusted odds ratios and 95% confidence intervals (CIs).
We used multivariate logistic regression to determine the factors associated with not having a Pap test. Variables that were associated in the bivariate analysis with not having a Pap test (P < 0.1) were eligible for inclusion in multivariate analysis. On the basis of estimated logit plots, we included age as a continuous variable. Logistic regression was performed by using forward selection with a P value cutoff of 0.05. We also assessed all possible 2-way interactions between variables, with a P value cutoff of 0.05. We calculated adjusted odds ratios (AORs) and 95% CIs for the odds of not having received a Pap test in the past year. We controlled for site and year of interview (data not presented) and race/ethnicity.
From May 2000 through June 2004, 10,977 persons were offered enrollment in the Supplement to HIV/AIDS Surveillance project; 8681 (79%) accepted the interview and 2296 (21%) refused. Of those interviewed, 2548 (29%) were women. In sites with population-based recruitment methods, certain demographic information was available for those who refused to be interviewed. In these sites, those who refused were significantly more likely to be aged 30-39 years but not significantly different with respect to race/ethnicity or mode of transmission. Of the 2548 women interviewed, 131 were excluded from our analysis for the following reasons: 110 had a missing year for the date of their most recent pelvic exam or Pap test, 19 were interviewed less than 1 month after their HIV diagnosis, and 2 had a missing interview date. Thus, 2417 women met our analysis criteria. Those excluded from analysis, compared with those included, were significantly less likely to have had a history of abnormal Pap test findings or to have had a sexually transmitted disease during the past year and were more likely to have an unknown CD4 cell count or to have had their most recent pelvic exam performed somewhere other than their usual source of HIV care (Table 1).
Of the 2417 women included in our analysis, 69% were African American and 15% were Hispanic (Table 2). Median age was 39 years. Approximately 55% reported a household income of less than $10,000 per year, 83% had health insurance (data not shown), and 74% received their primary HIV care at a community or public clinic. At the time of interview, 556 (23%) had not received a Pap test during the year before the interview.
In bivariate analysis, drug and alcohol use, health insurance status, sexual orientation, time since HIV diagnosis, and previous hysterectomy were not significantly associated with Pap screening. We found a linear association between age group and the proportion of women who had not received a Pap test (Fig. 1). Education, household income, exposure category, primary site of HIV care, CD4 cell count, history of abnormal Pap test, pregnancy, clinical category, history of sexually transmitted disease, and location of most recent pelvic exam were associated with cervical cancer screening (Table 2).
In the logistic regression analysis, increasing age (AOR = 1.3 per 10 years, CI: 1.1 to 1.4) and most recent CD4 count of <200 cells per microliter (AOR = 1.6, CI: 1.2 to 2.1) or unknown CD4 cell count (AOR = 1.4, CI: 1.1 to 1.7), both compared with CD4 count of ≥200 cells per microliter, were independently associated with not having a Pap test in the past year (Table 2). The odds of not having a Pap test in the past year were lower for women with a history of abnormal Pap test findings (AOR = 0.6, CI: 0.5 to 0.8) and those who were pregnant during the past year (AOR = 0.6, CI: 0.4 to 1.0).
Two significant 2-way interactions were identified (Table 2). The first of these was the interaction of clinical category with history of sexually transmitted disease. Women with HIV infection (not AIDS) and a sexually transmitted disease during the past year, compared with women who had not had a sexually transmitted disease, were more likely to have received a Pap test in the past year (AOR = 0.4 for not receiving a test, CI: 0.2 to 0.6).
Race/ethnicity and location of most recent pelvic exam also interacted (Table 2). For 1096 (45.3%) of the study participants, their most recent pelvic exam was performed at their usual source of HIV care; these women were less likely to have a Pap test, although the level of effect depended on the woman's race or ethnicity. The highest odds of not receiving a Pap test were those for Hispanic women whose most recent pelvic exam was not performed at their usual source of HIV care (AOR = 4.8, CI: 2.7 to 8.4); the next highest odds were those for white women (AOR = 2.3, CI: 1.8 to 2.9). However, the odds of not having a Pap test were also increased for African American women (AOR = 1.7, CI: 1.1 to 2.5) and women of other races (AOR = 2.1, CI: 1.1 to 4.1) whose most recent pelvic exam was not performed at their usual source of HIV care.
When the logistic regression analysis was repeated after excluding women whose diagnosis had been made less than 6 months before the interview, the results did not change substantively.
Nearly a quarter of HIV-infected women in our study population had not received the recommended cervical cancer screening during the year before interview. This finding is consistent with that of Stein et al,20 who found that 19% of HIV-infected women in care for HIV infection in the United States reported not receiving cervical cancer screening during the past year. In large studies of the general population, 14%-20% of women reported not receiving cervical cancer screening during the 3 years before interview.21,22
Our estimate may be an overestimate of the level of cervical cancer screening among HIV-infected women for 3 reasons. First, largely because of the recruitment methods used, 98% of the women in our study were in care for HIV infection, and women who are not in care for HIV infection are probably less likely to receive cervical cancer screening, as women in the general population who report no contact with a primary care provider during the past year or no usual source of care are less likely to have received a Pap test.23 Second, women overreport cervical cancer screening by as much as a quarter to a third.24-26 Finally, although HIV infection had been diagnosed for a third of the women in our study less than 1 year before interview, and according to HIV treatment guidelines, these women should have received 2 Pap tests during that time; the prevalence of screening in this group was not increased. This finding suggests that adherence to screening recommendations may be even lower than our analysis indicates.
Three main factors were associated with not receiving a Pap test during the year before interview. The first of these was having received the most recent pelvic exam performed somewhere other than one's usual source of HIV care. Likewise, the study by Stein et al20 found that receiving gynecologic care somewhere other than the primary source of HIV care was associated with not receiving a Pap test. For women who do not receive their gynecologic care at their usual source of HIV care, ensuring that the recommended screening requires additional coordination by the physician and the patient in the form of referrals and scheduling and attending additional appointments, all of which may serve as barriers to screening. In fact, in a study of HIV-infected women in care at 1 clinic, although 82% had been referred for a Pap test, only 58% received it.27 Location of the most recent pelvic exam, though significant for women of all races and ethnicities, was particularly important for Hispanic women. Our study cannot provide the reason for this, but if many of these women have limited English proficiency, this finding could relate to difficulty in navigating the health care system or to limitations in communicating to their health care providers whether and when they have received a Pap test.
The second factor associated with not receiving a Pap test was increasing age. For the general population, recommendations state that cervical cancer screening may be discontinued or conducted less frequently among older women who are at low risk.28,29 Although study findings differ as to the influence of age on the prevalence of cervical cytologic abnormalities in HIV-infected women,4,7 it is clear that compared with the general population, HIV-infected women of increasing age are still at high risk overall. The relationship between increased age and increased odds of not receiving a Pap test was linear and present across the spectrum of ages, indicating that attention needs to be given to ensuring Pap screening for HIV-infected women of all ages.
The last major factor we found to be associated with not receiving a Pap test was a low CD4 cell count. Women with low CD4 cell counts are at increased risk of many other illnesses, including infections and malignancies. Because of competing priorities, preventive care for these women may be given lower priority than in other HIV-infected women. However, it is important to remember that these women are at higher risk of HPV infection and abnormal Pap test findings;7,11 thus, cervical cancer screening should be a high priority.
The recently approved HPV vaccine, licensed for use in females aged 9-26 years, may, in the coming decades, lead to changes in the rates of cervical cytologic abnormalities and invasive cervical cancer in HIV-infected women, particularly as we see the benefits for women vaccinated against HPV before they become sexually active. Although the vaccine is most effective when administered before the onset of sexual activity, most young women, even if already infected with some types of HPV, will receive at least partial benefit from the vaccine. Moreover, the vaccine is noninfectious and thus can be safely administered to women who are HIV infected.30 Nevertheless, because the HPV vaccine does not protect women who have already been infected with types of HPV that place women at the highest risk for cervical cancer and because the vaccine, even when administered before infection with HPV, does not protect against all types of HPV, it is important to continue to perform regular cervical cancer screening among women who have been vaccinated.30
This study is subject to several limitations. The data are not representative of all HIV-infected women in the United States: the data are limited to women in 18 states, which were not randomly selected, and the participants in the Supplement to HIV/AIDS Surveillance project were not randomly selected. Because of the facility-based recruitment methods used in some areas, the sample may underrepresent women who are not in care. As previously mentioned, the rate of screening for these women is likely to be lower than the rate for HIV-infected women in care23; therefore, our estimate of cervical cancer screening may be high. In addition, we did not check medical records to confirm the women's self-reports of Pap testing; in other studies, women have overreported cervical cancer screening.24-26 Therefore, the data may be subject to recall bias, and there may have been misclassification, another reason that this may be an overestimate of the rate of cervical cancer screening in this population. Furthermore, for the women who were interviewed for the Supplement to HIV/AIDS Surveillance, but who were excluded from this analysis, it was significantly more likely that their CD4 cell count was unknown and that their most recent pelvic exam was not performed by their usual HIV care provider. On the other hand, these women were significantly less likely to have a history of abnormal Pap test findings or a sexually transmitted disease during the past year. All these factors, which suggest that these women were less likely to have received a Pap test, contribute to the possibility that ours is an overestimate of cervical cancer screening. Moreover, for the women whose HIV diagnosis was made during the year before interview, we did not determine whether their most recent Pap test was performed before or after diagnosis. Therefore, for the women whose Pap test was performed before diagnosis, cervical cancer screening may not represent adherence to HIV screening guidelines. Finally, the Supplement to HIV/AIDS Surveillance project did not assess whether a Pap test had been offered; therefore, we were unable to distinguish whether not receiving a Pap test was associated with refusal or with other patient-related factors.
Nearly a quarter of the HIV-infected women in our study had not received the recommended cervical cancer screening during the year before interview, and we believe this to be a minimum estimate of the lack of adherence to screening recommendations. To increase cervical cancer screening among HIV-infected women, HIV care providers should ensure that cervical cancer screening is performed twice in the year after diagnosis and annually thereafter, being particularly alert to ensuring Pap tests for women of increasing age, women with low CD4 cell counts, and women who receive their gynecologic care at a location other than their usual source of HIV care. Additionally, educating primary care providers and gynecologists regarding the recommendations for cervical cancer screening for HIV-infected women and how they differ from general cervical cancer screening recommendations (which allow for less frequent screening in some circumstances) may increase screening among HIV-infected women who receive their gynecologic care from these providers. Likewise, informing HIV-infected women about current recommendations for an annual Pap test may be particularly helpful for those receiving gynecologic care elsewhere. Finally, integrating gynecologic care into primary HIV care may be an important tool for increasing adherence to the recommended cervical cancer screening among HIV-infected women.
We gratefully acknowledge the contributions of Glenn Nakamura and the Supplement to HIV/AIDS Surveillance project principal investigators and project officers: Vjollca Berisha and Rick DeStephens, Arizona Department of Public Health; Aaron Roome, Connecticut Department of Public Health; James Welch, Delaware Department of Public Health; Arthur Davidson, Denver Health and Hospital Authority; Jeffrey Lenox and Alan Fann, Emory University School of Medicine; Rebecca Grigg and Pam Lowell, Florida Department of Health; Marcia Wolverton, Houston Department of Health and Human Services; Fran Eury, Illinois Department of Public Health; Jeni Mulqueen, Anthony Merriweather, and Gail Hansen, Kansas Department of Health and Environment; Amy Rock Wohl and Denise Johnston, Los Angeles County Department of Health; Ellen Caldeira, Maryland Department of Health and Mental Hygiene; Eve Mokotoff, Sha Juan Colbert, and Shanell McGoy, Michigan Department of Community Health; Richard Danila and Don Stiepan, Minnesota Department of Public Health; Sally D'Errico, New Jersey Department of Health; Mack Sewell, New Mexico Department of Public Health; Kathleen Brady, Philadelphia Department of Public Health; Terri Stephens, South Carolina Department of Health and Environmental Control; Sharon Melville and Sylvia Odem, Texas Department of Health; and Maria Courogen, Washington State Department of Health.
1. Glynn M, Rhodes P. Estimated HIV prevalence in the United States at the end of 2003. Paper presented at: National HIV Prevention Conference; June 2005; Atlanta, GA.
2. Sun XW, Kuhn L, Ellerbrock TV, et al. Human papillomavirus infection in women infected with the human immunodeficiency virus. N Engl J Med
3. Minkoff HL, Eisenberger-Matityahu D, Feldman J, et al. Prevalence and incidence of gynecologic disorders among women infected with human immunodeficiency virus. Am J Obstet Gynecol
4. Wright TC Jr, Ellerbrock TV, Chiasson MA, et al. Cervical intraepithelial neoplasia in women infected with human immunodeficiency virus: prevalence, risk factors, and validity of Papanicolaou smears. New York Cervical Disease Study. Obstet Gynecol
5. Maiman M, Fruchter RG, Sedlis A, et al. Prevalence, risk factors, and accuracy of cytologic screening for cervical intraepithelial neoplasia in women with the human immunodeficiency virus. Gynecol Oncol
6. Danso D, Lyons F, Bradbeer C. Cervical screening and management of cervical intraepithelial neoplasia in HIV-positive women. Int J STD AIDS
. 2006;17:579-584; quiz 585-587.
7. Massad LS, Riester KA, Anastos KM, et al. Prevalence and predictors of squamous cell abnormalities in Papanicolaou smears from women infected with HIV-1. J Acquir Immune Defic Syndr
8. Ellerbrock TV, Chiasson MA, Bush TJ, et al. Incidence of cervical squamous intraepithelial lesions in HIV-infected women. JAMA
9. Schuman P, Ohmit SE, Klein RS, et al. Longitudinal study of cervical squamous intraepithelial lesions in human immunodeficiency virus (HIV)-seropositive and at-risk HIV-seronegative women. J Infect Dis
10. Maiman M, Fruchter RG, Guy L, et al. Human immunodeficiency virus infection and invasive cervical carcinoma. Cancer
11. Palefsky JM, Minkoff H, Kalish LA, et al. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst
12. Engels EA, Pfeiffer RM, Goedert JJ, et al. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS
13. Centers for Disease Control and Prevention. USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: a summary. MMWR Recomm Rep
14. Centers for Disease Control and Prevention. 1997 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. MMWR Recomm Rep
15. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among HIV-infected persons-2002: recommendations of the U.S. Public Health Service and the Infectious Diseases Society of America. MMWR Recomm Rep
16. Centers for Disease Control and Prevention. 1998 guidelines for treatment of sexually transmitted diseases. MMWR Recomm Rep
17. Centers for Disease Control and Prevention. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus: U.S. Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA). MMWR Recomm Rep
. 1999;48(RR-10):1-59, 61-56.
18. Aberg JA, Gallant JE, Anderson J, et al. Primary care guidelines for the management of persons infected with human immunodeficiency virus: recommendations of the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis
19. Buehler JW, Diaz T, Hersh BS, et al. The supplement to HIV-AIDS Surveillance project: an approach for monitoring HIV risk behaviors. Public Health Rep
. 1996;111(suppl 1):133-137.
20. Stein MD, Cunningham WE, Nakazono T, et al. Screening for cervical cancer in HIV-infected women receiving care in the United States. J Acquir Immune Defic Syndr
21. Breen N, Wagener DK, Brown ML, et al. Progress in cancer screening over a decade: results of cancer screening from the 1987, 1992, and 1998 National Health Interview Surveys. J Natl Cancer Inst
22. Coughlin SS, King J, Richards TB, et al. Cervical cancer screening among women in metropolitan areas of the United States by individual-level and area-based measures of socioeconomic status, 2000 to 2002. Cancer Epidemiol Biomarkers Prev
23. Hewitt M, Devesa SS, Breen N. Cervical cancer screening among U.S. women: analyses of the 2000 National Health Interview Survey. Prev Med
24. Sawyer JA, Earp JA, Fletcher RH, et al. Accuracy of women's self-report of their last Pap smear. Am J Public Health
25. McPhee SJ, Nguyen TT, Shema SJ, et al. Validation of recall of breast and cervical cancer screening by women in an ethnically diverse population. Prev Med
26. McGovern PG, Lurie N, Margolis KL, et al. Accuracy of self-report of mammography and Pap smear in a low-income urban population. Am J Prev Med
27. Sheth AN, Moore RD, Gebo KA. Provision of general and HIV-specific health maintenance in middle aged and older patients in an urban HIV clinic. AIDS Patient Care STDS
28. Smith RA, Cokkinides V, Eyre HJ. American Cancer Society guidelines for the early detection of cancer, 2003. CA Cancer J Clin
29. U.S. Preventive Services Task Force. Guide to Clinical Preventive Services
. 2nd ed. Washington, DC: Office of Disease Prevention and Health Promotion; 1996.
30. Markowitz LE, Dunne EF, Saraiya M, et al. Quadrivalent human papillomavirus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep