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Human Immunodeficiency Virus (HIV)– and Non-HIV–Associated Immunosuppression and Risk of Cervical Neoplasia

Silverberg, Michael, J., PhD; Leyden, Wendy, A., MPH; Chi, Aileen, PharmD; Gregorich, Steven, PhD; Huchko, Megan, J., MD; Kulasingam, Shalini, PhD; Kuppermann, Miriam, PhD; Seto, Anna, PharmD; Smith-McCune, Karen, K., MD; Sawaya, George, F., MD

doi: 10.1097/AOG.0000000000002371
Contents: Original Research

OBJECTIVE: To estimate the risk of cervical intraepithelial neoplasia grade 2, 2–3, 3, adenocarcinoma in situ, or cancer (CIN 2 or worse) among women with human immunodeficiency virus (HIV)– and non-HIV–associated immunosuppression.

METHODS: We performed a case–control study of 20,146 women with incident CIN 2 or worse and 5:1 age-matched, incidence-density selected women in a control group (n=100,144) enrolled in an integrated health care system from 1996 to 2014. Adjusted rate ratios (RRs) from conditional logistic regression were obtained for HIV status (stratified by CD4+ T-cells), solid organ transplant history, and immunosuppressive medication use.

RESULTS: Risk of CIN 2 or worse was increased among women with HIV (n=36 women in the case group and 79 women in the control group; adjusted RR 2.0, 95% CI 1.3–3.0) compared with those without HIV and in solid organ transplant recipients (n=51 women in the case group and 68 women in the control group; RR 3.3, 95% CI 2.3–4.8) compared with women without a prior transplant. The highest risks were among women with HIV and less than 200 CD4+ T-cells/microliter (n=9 women in the case group and eight women in the control group; RR 5.6, 95% CI 2.1–14.7) compared with those without HIV and in solid organ transplant recipients prescribed three or greater immunosuppressive medication classes (n=32 women in the case group and 33 women in the control group; RR 4.1, 95% CI 2.5–6.8) compared with women without a prior transplant and zero medication classes. No increased risks were observed for women with HIV and 500 or greater CD4+ T-cells/microliter (n=9 women in the case group and 43 women in the control group; RR 0.8, 95% CI 0.4–1.7) compared with those without HIV or women without prior solid organ transplantation prescribed two or fewer immunosuppressive medication classes (n=1,262 women in the case group and 6,100 women in the control group; RR 0.95, 95% CI 0.89–1.01) compared with women without and a prior transplant and zero medication classes.

CONCLUSION: Risk of CIN 2 or worse is increased in women with a prior solid organ transplant or who have HIV and CD4+ cells/microliter less than 500 but not in women with HIV and higher CD4+ levels or in women without a prior solid organ transplant but who are prescribed only one or two immunosuppressive medication classes.

Cervical neoplasia risk is not increased in women with human immunodeficiency virus with high CD4+ counts or in women without solid organ transplantation prescribed two or fewer immunosuppressive medication classes.

Division of Research, Kaiser Permanente, Oakland, California; the Department of Epidemiology and Biostatistics, the School of Pharmacy, the Department of Medicine, and the Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California; the Department of Obstetrics and Gynecology and the Global Health Institute, Duke University, Durham, North Carolina; and the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota.

Corresponding author: Michael J. Silverberg, PhD, Research Scientist III, Kaiser Permanente, Division of Research, 2000 Broadway, Oakland, CA 94612; email: Michael.J.Silverberg@kp.org.

Supported by the National Cancer Institute (R01CA169093).

The study sponsor had no role in study design, data collection, analysis, interpretation of data, or manuscript development.

Financial Disclosure The authors did not report any potential conflicts of interest.

Presented in part at the Conference on Retroviruses and Opportunistic Infections, February 22–25, 2016, Boston, Massachusetts; and as a poster at the 31st International Papillomavirus Conference, February 28–March 5, 2017, Cape Town, South Africa.

Each author has indicated that he or she has met the journal's requirements for authorship.

© 2018 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.