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Natural History of Cervical Intraepithelial Neoplasia-2 in HIV-Positive Women of Reproductive Age

Colie, Christine, MD*; Michel, Katherine G., PhD, MPH; Massad, Leslie S., MD; Wang, Cuiwei, MS; D'Souza, Gypsyamber, PhD§; Rahangdale, Lisa, MD, MPH; Flowers, Lisa, MD; Milam, Joel, PhD#; Palefsky, Joel M., MD**; Minkoff, Howard, MD††; Strickler, Howard D., MD, MPH‡‡; Kassaye, Seble G., MD, MS

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15, 2018 - Volume 79 - Issue 5 - p 573–579
doi: 10.1097/QAI.0000000000001865

Objective: To evaluate the natural history of treated and untreated cervical intraepithelial neoplasia-2 (CIN2) among HIV-positive women.

Methods: Participants were women enrolled in the Women's Interagency HIV Study between 1994 and 2013. One hundred four HIV-positive women diagnosed with CIN2 before age 46 were selected, contributing 2076 visits over a median of 10 years (interquartile range 5–16). The outcome of interest was biopsy-confirmed CIN2 progression, defined as CIN3 or invasive cervical cancer. CIN2 treatment was abstracted from medical records.

Results: Most women were African American (53%), current smokers (53%), and had a median age of 33 years at CIN2 diagnosis. Among the 104 HIV-positive women, 62 (59.6%) did not receive CIN2 treatment. Twelve HIV-positive women (11.5%) showed CIN2 progression to CIN3; none were diagnosed with cervical cancer. There was no difference in the median time to progression between CIN2-treated and CIN2-untreated HIV-positive women (2.9 vs. 2.7 years, P = 0.41). CIN2 treatment was not associated with CIN2 progression in multivariate analysis (adjusted hazard ratio 1.82; 95% confidence interval: 0.54 to 7.11), adjusting for combination antiretroviral therapy and CD4+ T-cell count. In HIV-positive women, each increase of 100 CD4+ T cells was associated with a 33% decrease in CIN2 progression (adjusted hazard ratio 0.67; 95% confidence interval: 0.47 to 0.88), adjusting for CIN2 treatment and combination antiretroviral therapy.

Conclusions: CIN2 progression is uncommon in this population, regardless of CIN2 treatment. Additional studies are needed to identify factors to differentiate women at highest risk of CIN2 progression.

*Department of Obstetrics and Gynecology, Georgetown University Medical Center, Washington, DC;

Department of Medicine, Georgetown University, Washington, DC;

Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO;

§Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD;

Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, NC;

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA;

#Department of Preventative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA;

**Department of Medicine, University of California, San Francisco, CA;

††Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY; and

‡‡Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.

Correspondence to: Christine Colie, MD, Department of Obstetrics and Gynecology, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington DC 20007 (e-mail:

WIHS (principal investigators): UAB-MS WIHS (Michael Saag, Mirjam-Colette Kempf, and Deborah Konkle-Parker), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (H.M. and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen and Audrey French), U01-AI-034993; Metropolitan Washington WIHS (Seble Kassaye), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women's HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (J.M.), and U01-HD-032632 (WIHS I – WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the NIH Office of Research on Women's Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA). Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the NIH under Award Number TL1TR001431.

J.M.P. owns stock options in Ubiome; receives grant support and acts as consultant for Antiva; receives grant support, acts as consultant, and owns stock in Agenovir; receives grant support, travel support and is on an advisory board for Merck & Co. The remaining authors have no funding or conflicts of interest to disclose.

C.C. and K.G.M. have contributed equally to this work.

The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH).

IRB Status: Approved under at all sites before study began.

The NIH did not take part in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the article for publication.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received March 02, 2018

Accepted September 03, 2018

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