Starting to have sexual intercourse is associated with increases in cervicovaginal immune mediators in young women: a prospective study and meta-analysis

Sean M. Hughes, Department of Obstetrics and Gynecology, University of Washington, Seattle, United States.
Claire N. Levy, Department of Obstetrics and Gynecology, University of Washington, Seattle, United States.
Fernanda L. Calienes, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
Katie A. Martinez, Department of Obstetrics and Gynecology, University of Washington, Seattle, United States.
Stacy Selke, Department of Laboratory Medicine & Pathology, University of Washington, Seattle, United States.
Kenneth Tapia, Department of Global Health, University of Washington, Seattle, United States.
Bhavna H. Chohan, Department of Global Health, University of Washington, Seattle, United States.
Lynda Oluoch, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Catherine Kiptinness, Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Anna Wald, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
Mimi Ghosh, Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, United States.
Liselotte Hardy, Department of Clinical Sciences, Unit of Tropical Bacteriology, Institute of Tropical Medicine, Antwerp, Belgium.
Kenneth Ngure, Department of Global Health, University of Washington, Seattle, United States.
Nelly R. Mugo, Department of Global Health, University of Washington, Seattle, United States.
Florian Hladik, Department of Obstetrics and Gynecology, University of Washington, Seattle, United States.
Alison C. Roxby, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States.

Document Type

Journal Article

Publication Date

10-25-2022

Journal

eLife

Volume

11

DOI

10.7554/eLife.78565

Keywords

adolescent girls and young women; cytokines; genital immunity; human; immune activation; immunology; inflammation; medicine; mucosal immunity; sexual intercourse

Abstract

Background: Adolescent girls and young women (AGYW) are at high risk of sexually transmitted infections (STIs). It is unknown whether beginning to have sexual intercourse results in changes to immune mediators in the cervicovaginal tract that contribute to this risk. Methods: We collected cervicovaginal lavages from Kenyan AGYW in the months before and after first penile-vaginal sexual intercourse and measured the concentrations of 20 immune mediators. We compared concentrations pre- and post-first sex using mixed effect models. We additionally performed a systematic review to identify similar studies and combined them with our results by meta-analysis of individual participant data. Results: We included 180 samples from 95 AGYW, with 44% providing only pre-first sex samples, 35% matched pre and post, and 21% only post. We consistently detected 19/20 immune mediators, all of which increased post-first sex (p<0.05 for 13/19; Holm-Bonferroni-adjusted p<0.05 for IL-1β, IL-2, and CXCL8). Effects remained similar after excluding samples with STIs and high Nugent scores. Concentrations increased cumulatively over time after date of first sex, with an estimated doubling time of about 5 months.Our systematic review identified two eligible studies, one of 93 Belgian participants, and the other of 18 American participants. Nine immune mediators were measured in at least two-thirds of studies. Meta-analysis confirmed higher levels post-first sex for 8/9 immune mediators (p<0.05 for six mediators, most prominently IL-1α, IL-1β, and CXCL8). Conclusions: Cervicovaginal immune mediator concentrations were higher in women who reported that they started sexual activity. Results were consistent across three studies conducted on three different continents. Funding: This research was funded by R01 HD091996-01 (ACR), by P01 AI 030731-25 (Project 1) (AW), R01 AI116292 (FH), R03 AI154366 (FH) and by the Center for AIDS Research (CFAR) of the University of Washington/Fred Hutchinson Cancer Research Center AI027757.

Department

Epidemiology

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