HPV and Other Microbiota; Who’s Good and Who’s Bad: Effects of the Microbial Environment on the Development of Cervical Cancer—A Non-Systematic Review

Abstract

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.

Identification of Oxidative Stress-Associated Molecular Subtypes and Signature for Predicting Survival Outcome of Cervical Squamous Cell Carcinoma

“…HPV infection is a pathogenic factor of cervical cancer and other cancers, but its mechanism is still unclear [ 6 ]. At the same time, some studies have shown that not all HPV infections lead to cervical cancer, which suggested that in addition to HPV infection, cervical cancer also involves other factors such as genetics and environment [ 7 , 8 ]. In the 30 years since the cervical cancer screening programme was introduced, both cervical cancer incidence and death rates have fallen by more than 50% [ 9 , 10 ].…”

Aerobic vaginitis is associated with carbonic anhydrase IX in cervical intraepithelial neoplasia

“…Lactobacilli spp. increase adenosine and cytosine levels and reduce inflammation 65 , but they are suppressed in msAV and BV cases. Vaginal microbiome called community state type IV with decreased number of Lactobacilli spp.…”

Risk Factors of Preterm Birth in Women After Local Treatment of Cervical Intraepithelial Neoplasia – a Retrospective Cohort Study

“…A persistent infection with the high-risk HPV types 16 and 18 during pregnancy was, independent of cervical treatment, associated with an increased risk of PTB (aOR 3.72 [95% CI 1.47–9.39]). Both HPV persistence and PTB share some risk factors like an inflammatory vaginal milieu due to bacterial vaginosis, aerobic vaginitis and cervicitis following infection with chlamydia trachomatis 10 20 21 22 23 24 25 26 . Therefore, it remains unclear if the HPV infection is directly causal for the increased risk of PTB or if it is only an indicator for a high-risk milieu.…”