Prevalence and Risk Factors for High-Risk Human Papillomavirus Infection and Cervical Disorders: Baseline Findings From an Human Papillomavirus Cohort Study.

BACKGROUND: A persistent infection by high-risk human papillomavirus (HR-HPV) is a prerequisite for the development of cervical neoplasms; however, most studies have focused on risk factors associated with HPV-16 and HPV-18 only. OBJECTIVES: We assessed the association of risk factors with the prevalence of HPV-16, HPV-18, and non-16/18 HR-HPV infection and with the occurrence of cervical lesions in the baseline of a cohort study of HPV persistence in a Mexican population. METHODS: Cross-sectional study within the baseline of a 5-year dynamic cohort study of HR-HPV persistence in women with an abnormal cytology study result from 2015 to 2021. HPV DNA was detected using the Anyplex II HPV 28 kit. Data on lifestyle, sociodemographic, and reproductive factors were assessed using bivariate and multivariate analyses to determine the association of risk factors with HR-HPV infection status and histopathologic diagnosis. RESULTS: A total of 373 women were included in the study. The overall prevalence of HR-HPV infection was 69.97%. The most prevalent HR-HPV genotypes, including single and multiple infections, were HPV-53 (13.4%), HPV-16 (11.8%), HPV-58 (10.9%), HPV-31 (10.9%), and HPV-66 (10.7%). We found 90 multiple HR-HPV infection patterns, all of them with α-6 and -9 species. Significant associations of multiple HPV-16 and non-16/18 HR-HPV infections were found with marital status, number of lifetime sexual partners, and smoking history. The most prevalent genotype in CIN1 and CIN2 patients was HPV-16. No association was found between biological plausibility risk factors and cervical lesions. CONCLUSIONS: The risk factors for non-16/18 HR-HPV multiple infections are no different than those linked to HPV-16 multiple infections.

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-ß1, 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 ß-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 ß-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-ß1 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.

The SNP at -592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development.

BACKGROUND: Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL). METHODS: Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. RESULTS: No significant differences were found between genotype frequencies at loci -819, -1082, and -1352. Individuals carrying at least one copy of risk allele A of polymorphism -592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A. CONCLUSIONS: The -592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.