Abstract
Postmenopausal women often suffer from vaginal symptoms associated with atrophic vaginitis. Additionally, gynecologic cancer survivors may live for decades with additional, clinically significant, persistent vaginal toxicities caused by cancer therapies, including pain, dyspareunia, and sexual dysfunction. The vaginal microbiome (VM) has been previously linked with vaginal symptoms related to menopause (i.e. dryness). Our previous work showed that gynecologic cancer patients exhibit distinct VM profiles from healthy women, with low abundance of lactobacilli and prevalence of multiple opportunistic pathogenic bacteria. Here we explore the association between the dynamics and structure of the vaginal microbiome with the manifestation and persistence of vaginal symptoms, during one year after completion of cancer therapies, while controlling for clinical and sociodemographic factors. We compared cross-sectionally the vaginal microbiome in 134 women, 64 gynecologic patients treated with radiotherapy and 68 healthy controls, and we longitudinally followed a subset of 52 women quarterly (4 times in a year: pre-radiation therapy, 2, 6 and 12 months post-therapy). Differences among the VM profiles of cancer and healthy women were more pronounced with the progression of time. Cancer patients had higher diversity VMs and a variety of vaginal community types (CTs) that are not dominated by Lactobacilli, with extensive VM variation between individuals. Additionally, cancer patients exhibit highly unstable VMs (based on Bray-Curtis distances) compared to healthy controls. Vaginal symptoms prevalent in cancer patients included vaginal pain (40%), hemorrhage (35%), vaginismus (28%) and inflammation (20%), while symptoms such as dryness (45%), lack of lubrication (33%) and dyspareunia (32%) were equally or more prominent in healthy women at baseline. However, 24% of cancer patients experienced persistent symptoms at all time points, as opposed to 12% of healthy women. Symptom persistence was strongly inversely correlated with VM stability; for example, patients with persistent dryness or abnormally high pH have the most unstable microbiomes. Associations were identified between vaginal symptoms and individual bacterial taxa, including: Prevotella with vaginal dryness, Delftia with pain following vaginal intercourse, and Gemillaceaea with low levels of lubrication during intercourse. Taken together our results indicate that gynecologic cancer therapy is associated with reduced vaginal microbiome stability and vaginal symptom persistence.
Highlights
Vaginal symptoms that are highly pervasive in postmenopausal women (Huang et al, 2010; Palacios et al, 2018) include dryness, burning, itching, vaginal discomfort, pain and burning when urinating, dyspareunia, recurrent urinary tract infections and spotting during intercourse
Gynecologic cancer patients and control groups had no significant differences in age, body mass index (BMI), or racial distributions (Table 1)
Postmenopausal women diagnosed with gynecologic cancers presented a different symptomatology and symptom persistence
Summary
Vaginal symptoms that are highly pervasive (reported by 40%60%) in postmenopausal women (Huang et al, 2010; Palacios et al, 2018) include dryness, burning, itching, vaginal discomfort, pain and burning when urinating, dyspareunia, recurrent urinary tract infections and spotting during intercourse. Several of those symptoms are further exacerbated in gynecologic cancer patients (which are typically already menopausal), as cancer therapies pose a significant disturbance in the vaginal environment. Radiation therapy is associated with vaginal toxicities including loss of lubrication, dyspareunia, vaginal itching, discharge, and cystitis, all of which may lead to increased vaginal discomfort, infection, diminished sexual activity and decreased quality of life (Leroy et al, 2012; Klopp et al, 2014; Karabuga et al, 2015)
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