Preliminary Identification of the Aerobic Cervicovaginal Microbiota in Mexican Women With Cervical Cancer as the First Step Towards Metagenomic Studies

Abstract

Cervical cancer (CC) is considered a public health problem. Recent studies have evaluated the possible relationship between the cervicovaginal microbiome and gynecologic cancer but have not studied the relationship between aerobic bacterial communities and neoplasia. The study aimed to identify the cultivable aerobic bacterial microbiota in women with cervical cancer as a preliminary approach to the metagenomic study of the cervicovaginal microbiome associated with cervical cancer in Mexican women. An observational cross-sectional study was conducted, including 120 women aged 21-71 years, divided into two study groups, women with locally advanced CC (n=60) and women without CC (n=60). Sociodemographic, gynecological-obstetric, sexual, and habit data were collected. Cervicovaginal samples were collected by swabbing, from which standard microbiological methods obtained culturable bacteria. The strains were genetically characterized by PCR-RFLP of the 16S rRNA gene and subsequently identified by sequencing the same gene. Variables regularly reported as risk factors for the disease were found in women with CC. Differences were found in the prevalence and number of species isolated in each study group. Bacteria commonly reported in women with aerobic vaginitis were identified. There were 12 species in women with CC, mainly Corynebacterium spp. and Staphylococcus spp.; we found 13 bacterial species in the group without cancer, mainly Enterococcus spp. and Escherichia spp. The advanced stages presented a more significant number of isolates and species. This study provided a preliminary test for cervicovaginal metagenomic analysis, demonstrating the presence of aerobic cervicovaginal dysbiosis in women with CC and the need for more in-depth studies.

Disturbances of Vaginal Microbiome Composition in Human Papillomavirus Infection and Cervical Carcinogenesis: A Qualitative Systematic Review

“…Consistently, 12 species were found in women with Ca, mainly Corynebacterium spp. and Staphylococcus spp., based on the identification of the cultivable aerobic bacterial microbiota ( 17 ). Notably, inflammation is crucial for the progression of cervical cancer to cancer ( 53 , 54 ).…”

“…A dysbiotic microbiome dominated by aerobic species can create an inflammatory environment that is favorable for tissue damage. It can also drive pathology by promoting immune evasion that favors tumor cell survival ( 17 ). Apart from BV-related anaerobes, the enrichment of other genera, such as Streptococcus and Staphylococcus , should be considered in the interpretation of vaginal microbiota during cervical carcinogenesis, which has been discussed in previous studies ( 52 , 55 ).…”

“…Regarding specific taxa, the most common anaerobes were reported to be associated with HPV infection and cervical dysplasia (i.e., G. vaginals, Megasphaera, Prevotella, and Sneathia) (14), whereas Sneathia and Atopobium were found to be inconsistently abundant (15,16). Other members (i.e., Streptococcus, Staphylococcus, Corynebacterium, Clostridium) have also been reported to be associated with cervical lesions and Ca (17)(18)(19). Additionally, the presence of cervical lesions and Ca among women has been correlated with an increase in Lactobacillus iners (13,20) and a decrease in Lactobacillus jensenii and Lactobacillus crispatus (20).…”

Disbiosis cervico-vaginal en la pesquisa citológica de cáncer de cuello uterino

“…Además, en esta investigación, la mayor prevalencia (67,2%) de las cervicovaginitis se encontró entre los 20 y 50 años de los casos estudiados, siendo estadísticamente significativo, en relación a los otros grupos etarios (≤ 19 y > 60 años), lo cual podría deberse a diversos factores que influyen directamente en la variación de la microbiota vaginal y que son considerados de riesgo para el desarrollo de disbiosis, como la raza o grupo étnico, edad y fisiología hormonal (ciclo menstrual y embarazo), la actividad sexual (promiscuidad, no uso del condón, semen, espermicidas) y factores conductuales (uso frecuente de duchas vaginales, DIU), variedad de productos de higiene íntima, tabaquismo, alimentación y deficiencias nutricionales), entre otros. En consecuencia, todos estos factores podrían desencadenar un estado de disbiosis, mayor exposición y adquisición de infecciones de transmisión sexual y de proliferación y persistencia de organismos patógenos como Chlamydia, HIV, virus del herpes y HPV, además de un mayor riesgo para otras enfermedades de importancia clínica como el cáncer cervical [9,10,15,22,23,31].…”

“…Estos estados de disbiosis, especialmente cuando ocurren en pacientes jóvenes, están asociados a serios problemas de fertilidad, obstétricos y ginecológicos como infertilidad, rotura prematura de las membranas placentarias, parto prematuro, recién nacidos con bajo peso, muerte neonatal, variedad de infecciones de transmisión sexual y cáncer de cuello uterino [28,44]. Además de estas infecciones, la vaginitis aeróbica es una entidad clínica reconocida recientemente, aunque probablemente es lo que se ha informado tradicionalmente en la citología como vaginitis bacteriana y que puede confundirse clínicamente con la vaginosis bacteriana, que se define como una alteración de la microbiota vaginal, caracterizada por disminución de lactobacilos y una mayor cantidad de bacterias aeróbicas entéricas (E. coli, S. aureus, Streptococos del grupo B y del género Enterococcus), con niveles variables de inflamación y un papel desconocido en el origen de la enfermedad neoplásica cervical [7, 9,10]. Aunque no existen suficientes datos, se estima que la frecuencia general de la vaginitis aeróbica podría ser de hasta 50% en pacientes con CIN1 [9].…”