Cervical Microbiome and Cytokine Profile at Various Stages of Cervical Cancer: A Pilot Study.
Cervical cancer (CC) is caused by high-risk human papillomavirus persistence due to the immunosuppressive tumor microenvironment mediated by cytokines. Vaginal microbiota determines the presence of certain cytokines locally. We assessed the association between cervical microbiota diversity and the histopathological diagnosis of each stage of CC, and we evaluated mRNA cervical expression levels of IL-4, IL-6, IL-10, TGF-β1, TNF-α and IFN-γ across the histopathological diagnosis and specific bacterial clusters. We determined the cervical microbiota by high throughput sequencing of 16S rDNA amplicons and classified it in community state types (CST). Mean difference analyses between alpha-diversity and histopathological diagnosis were carried out, as well as a β-diversity analysis within the histological diagnosis. Cervical cytokine mRNA expression was analyzed across the CSTs and the histopathological diagnoses. We found a significant difference in microbiota's diversity in NCL-HPV negative women vs those with squamous intraepithelial lesions (SIL) and CC(p = 0.006, p = 0.036).When β-diversity was evaluated, the CC samples showed the highest variation within groups (p<0.0006) and the largest distance compared to NCL-HPV negative ones (p<0.00001). The predominant bacteria in women with normal cytology were L. crispatus and L. iners, whereas for SIL, it was Sneathia spp. and for CC, Fusobacterium spp. We found higher median cervical levels of IL-4 and TGF-β1 mRNA in the CST dominated by Fusobacterium spp. These results suggest that the cervical microbiota may be implicated in cervical cancer pathology. Further cohort studies are needed to validate these findings.
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Astride
A
Audirac-Chalifour
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Kirvis
K
Torres-Poveda
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Margarita
M
Bahena-Román
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Juan
J
Téllez-Sosa
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Jesús
J
Martínez-Barnetche
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Bernardo
B
Cortina-Ceballos
Private Health Center for Gynecology, Cuernavaca, Morelos, Mexico.
Guillermina
G
López-Estrada
Centro de Atención para la Salud de la Mujer (CAPASAM) (Center for Women's Health), Health Services of the State of Morelos, Cuernavaca, Mexico.
Karina
K
Delgado-Romero
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Ana I
AI
Burguete-García
Division of Clinical Research, Instituto Nacional de Cancerología (INCan), SS, Mexico City, Mexico.
David
D
Cantú
Division of Basic Research, Instituto Nacional de Cancerología (INCan), SS, Mexico City, Mexico.
Alejandro
A
García-Carrancá
Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública (INSP) (Chronic Infectious Diseases and Cancer Division, Center for Research on Infectious Diseases, National Institute of Public Health), Cuernavaca, Morelos, Mexico.
Vicente
V
Madrid-Marina
D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D064307:Microbiota; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D059467:Transcriptome; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology
D016207:Cytokines; C573415:IFNG protein, human; C508609:IL10 protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma