The Role of the Cervicovaginal and Gut Microbiome in Cervical Intraepithelial Neoplasia and Cervical Cancer

Abstract

The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.

A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome

“…There is a diverse microbial spectrum in the body complementing a microbiome that contains a complex mutualistic host-microbial relationship which play crucial roles in the development and physiological function of the body including immune system modulation and inflammation ( Sims et al., 2021 ; Wu et al., 2021 ; Zhou et al., 2021 ). Cervical microbiota has identified a diversity of microbial species as possible modifiers of the cytokine profile of the cervical microenvironment, especially during increased stress conditions including physical, mental, and emotional stress ( Curty et al., 2020 ).…”

“…Over the age of 65 years, insufficient sleep, disturbance of the biological clock, and long-term stress conditions can cause stress insomnia in women. Stress insomnia can reduce the ability to fight off a common cervicovaginal infection and increase the risk of developing cervical cancer ( Sims et al., 2021 ). Physiological stress and sleep disorder were shown to affect the level of cytokines and immune response, both produced and released during sleep and exerted direct effects on the microbiome ( Garbarino et al., 2021 ).…”

Microbiota changes: the unseen players in cervical cancer progression

“…Detailed insights follow in this review’s upcoming sections. There is an emerging body of literature suggesting that alterations in the vaginal microbiota may be linked to cervical cancer ( Klein et al, 2020b ; Norenhag et al, 2020 ; So et al, 2020 ; Tango et al, 2020 ; Kang et al, 2021 ; Sims et al, 2021 ; Wu et al, 2021 ; Zhou et al, 2021 ). Furthermore, numerous studies propose that the vaginal microbiota could play a crucial role in defending women against infections such as HPV, vulvovaginal candidiasis, and other sexually transmitted diseases ( Liu et al, 2013 ; Lewis et al, 2017 ; Arroyo Mühr et al, 2021 ; Kang et al, 2021 ).…”

“…The exploration of the human microbiome has been an exciting journey, with techniques evolving from 16S sequencing ( Audirac-Chalifour et al, 2016 ; Dareng et al, 2016 ; di Paola et al, 2017 ; Klein et al, 2020b ; Norenhag et al, 2020 ; So et al, 2020 ; Tango et al, 2020 ; Sims et al, 2021 ; Wu et al, 2021 ; Zhou et al, 2021 ), PCR ( Norenhag et al, 2020 ), and microarray ( Borgdorff et al, 2014 ; Norenhag et al, 2020 ) to cutting-edge methods like RNA-seq ( Kori and Arga, 2018 ; Klein et al, 2020a ; Chang et al, 2021 ) and Whole Genome Shotgun (WGS) ( Klein et al, 2020a ; Wei et al, 2021 ). A significant milestone in this journey was the commencement of the Human Microbiome Project (HMP) in 2008, which aimed to map the microbial landscape across various body parts, including the lower genital tract of healthy individuals ( Castanheira et al, 2021 ).…”

The immune system, cancer, and pathogens: It takes three to tango!

“…These alterations are mostly evident by changes in the patient's intestinal microbiome composition, even if there is no direct gastrointestinal involvement. As an example, from this issue of JIPO, Sims et al [7] reviewed the changes seen in the intestinal microbiome of women with HPV-related cervical cancer. Growing evidence suggests that microbiome alterations in patients with cancer might play a role in cancer progression, response to therapy, and even cancer-related symptoms.…”