Cervicovaginal immune mediators increase when young women begin to have sexual intercourse: a prospective study and meta-analysis

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 causes 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 effects models. Secondary analyses included adjustment for possible confounding factors. 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 (median increase 54%; p<0.05 for 13/19; Holm-Bonferroni-adjusted p<0.05 for IL-1β, IL-2 and CXCL8). Effects remained similar after adjusting for confounding factors including STIs and Nugent score.

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 2/3 studies. Meta-analysis confirmed higher levels post-first sex for 8/9 immune mediators (median increase 47%; p<0.05 for six mediators, most prominently IL-1α, IL-1β and CXCL8).

Conclusions

Cervicovaginal immune mediator concentrations increased after the beginning of sexual activity independently of confounding factors including STIs. Results were consistent across three studies conducted on three different continents.