The Impact of Vaginal Washing on Cervical Inflammation: A Randomized Controlled Trial
- Conditions
- Reproductive Behavior
- Interventions
- Behavioral: Vaginal washing cessation
- Registration Number
- NCT06615232
- Lead Sponsor
- University of Washington
- Brief Summary
Vaginal washing is a common practice that many women perceive as hygienic. However, vaginal washing has been linked to adverse reproductive health outcomes including increased HIV acquisition risk. The mechanism linking vaginal washing to HIV risk remains unknown, but may be related to increased inflammation caused by intravaginal washing practices. The primary objective of this study is to test the hypothesis that a vaginal washing cessation intervention will reduce concentrations of soluble inflammatory mediators in cervicovaginal fluid and total immune cells in mucosal tissue, reduce cervical epithelial disruption, and increase concentrations of protective vaginal Lactobacillus spp. compared to control.
- Detailed Description
Vaginal washing is a common practice that many women perceive as normal and hygienic. However, vaginal washing has been linked to adverse reproductive health outcomes. We were the first to identify an association between vaginal washing and HIV acquisition risk in our long-term open cohort study of women who engage in sex work in Mombasa, Kenya (Mombasa Cohort). Subsequent observational studies and a large individual participant data meta-analysis have supported this observation.
It has been hypothesized that the mechanism linking vaginal washing and HIV acquisition involves disruption of the vaginal microbiota. However, while some studies have demonstrated an association between vaginal washing and vaginal microbial disruption, others have not. We have found mixed evidence of an association between vaginal washing and higher concentrations of vaginal bacteria that have been associated with HIV acquisition. Together, these data suggest that there may be other mechanisms linking vaginal washing and HIV acquisition risk, such as a direct effect of vaginal washing on cervicovaginal inflammation, recruitment of HIV target cells, and disruption of the mucosal barrier. In our preliminary studies, we found an association between vaginal washing and higher concentrations of IL-1 beta in cervicovaginal fluid and CD4+ T cells in cervical biopsies that was independent of BV, leading us to hypothesize that vaginal washing may increase HIV susceptibility by causing persistent activation of the IL-1 pathway, recruitment of HIV-susceptible target cells, and disruption of the mucosal barrier.
Despite the potential harms of the practice, cultural and behavioral norms may make cessation of vaginal washing difficult. To address this challenge, we conducted a pilot intervention grounded in the transtheoretical model of behavioral change for reducing vaginal washing. After one month, all participants reported a reduction or cessation in vaginal washing practices, and at 6-12 months, 52% of women reported continued abstinence from vaginal washing. While the study was not powered to examine differences in biological outcomes related to vaginal washing, we observed fewer mucosal lesions by colposcopy, higher prevalences of cultivable Lactobacillus species (spp.), and lower concentrations of several pro-inflammatory cytokines.
The primary objective of this study is to identify the likely mechanisms linking vaginal washing and HIV acquisition risk. To achieve this objective, we will conduct a randomized controlled trial of a vaginal washing cessation intervention (based in the transtheoretical model of behavioral change) to determine if a reduction in vaginal washing leads to improved mucosal homeostasis and decreased cervicovaginal inflammation by measuring i) cervicovaginal cytokine concentrations; ii) cervical immune cells from biopsy specimens; iii) expression of mucins and epithelial tight junction proteins; iv) the presence of cultivable Lactobacillus spp; and, v) concentrations of select Lactobacillus spp.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- Female
- Target Recruitment
- 122
- Reports vaginal washing beyond the introitus in the past week
- Female, aged 18-50
- Presence of a cervix
- Informed consent obtained and form signed
- HIV-seronegative
- Non-pregnant (urine β-hCG negative)
- Willing to abstain from sex for 14 days after biopsy
- Post-menarche and pre-menopause
- <3 months postpartum or current breastfeeding
- Current menstruation (can enroll after menses)
- History of bleeding disorder
- Visible cervical abnormality requiring evaluation
- Medical contraindication to study protocol
- Visible cervicovaginal ulcers or lesions
- Positive test for gonorrhea, chlamydia, trichomonas, or wet preparation and examination findings indicating vulvovaginal candidiasis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Vaginal washing cessation (intervention) Vaginal washing cessation The intervention will consist of 3 small-group educational sessions focused on vaginal washing cessation.
- Primary Outcome Measures
Name Time Method Concentrations of cervicovaginal cytokines Collected at baseline (study enrollment, time zero), at the end of the intervention (study week 4) and 3 months after enrollment (study week 12) Cervicovaginal cytokines will be measured from cervicovaginal fluid (collected via Softcup insertion for 15 minutes) using the Luminex platform, which is a multiplex bead-based immunoassay.
Activated CD4+ T cells and antigen presenting cells per mg cervical biopsy tissue Collected at baseline (study enrollment, time zero), at the end of the intervention (study week 4) and 3 months after enrollment (study week 12) Digested cervical biopsy specimens will be stained and analyzed to detect immune cells of interest using flow cytometry
Percent cells expressing mucin or tight junction proteins Collected at baseline (study enrollment, time zero), at the end of the intervention (study week 4) and 3 months after enrollment (study week 12) Expression of mucin and tight junction proteins will be detected by immunofluorescent staining of fixed cervical biopsy tissue sections and quantified
Presence of cultivable Lactobacillus spp Collected at baseline (study enrollment, time zero), at the end of the intervention (study week 4) and 3 months after enrollment (study week 12) Rogosa and Columbia blood agars will be inoculated with vaginal swabs collected at study visits and the number of women with cultivable species quantified
Concentrations of Lactobacillus spp of interest Collected at baseline (study enrollment, time zero), at the end of the intervention (study week 4) and 3 months after enrollment (study week 12) Concentrations of Lactobacillus spp. of interest will be measured by qPCR performed on DNA extracted from vaginal swabs collected at study visits
- Secondary Outcome Measures
Name Time Method