Paramita Mandal

Association of Vaginal Microbiota and Sociodemographic Factors With Cervical Human Papillomavirus in the Eastern Region of India

ABSTRACTProlonged exposure to the High‐risk Human Papillomavirus (HPV) leads to the development of cervical carcinoma. Numerous factors aid in this virus's acquisition, persistence, and clearance. This study aims to determine the association of vaginal microbiota and socio‐demographic factors with oncogenic HPV infections among women from Eastern region of India. Cervical scrapes and vaginal swab samples were collected from women (n = 300) having some gynecological complaints with informed consent. Cervical cytology and HPV types were screened among them. A subset of samples (n = 12) were subjected for next generation sequencing based 16S rRNA profiling to determine the vaginal bacterial diversity among the HPV−positive and HPV−negative women with normal cervical cytology. The taxonomic profiling, diversity and relative abundance of bacterial species were determined subsequently. With appropriate statistical tests, vaginal bacterial diversity along with socio‐demographic risk factors was correlated with HPV infections. A PCR‐based approach further detected the bacterial taxa that were exclusively present among the groups in the whole data set. HPV infection was identified among 11.60% of individuals, with the dominance of HPV18 (80%) among carcinogenic HPV. 16S rRNA profiling revealed that the HPV‐positive group had lower abundance of Firmicutes phylum and higher abundance of Proteobacteria and Actinobacteria phyla than the HPV‐negative group. A positive correlation between Genus Acinetobacter and HPV positivity was established, presenting higher susceptibility for oncogenic HPV16/18 (p = 0.016; relative mean abundance = 19.67). PCR‐based detection of this genus in the whole data set (n = 300), a statistically significant association with oncogenic HPV16/18 infection (p ≤ 0.01, odds ratio (OR)= 22.48 [95% CI = 5.23–96.63]) was found. Among sociodemographic factors, Tobacco users (16.67%, 4/24; OR = 6.70 [95% CI: 1.86–24.18]; p = 0.001) and field‐workers (15.79%, 3/19; OR = 5.67 [95% CI: 1.40–22.99]; p = 0.007) were associated with a higher risk of HPV18 infections. Assessment of geography‐specific vaginal microbiota and other lifestyle induced risk factors might contribute to acquire chronic infection of oncogenic HPV and progression to cervical cancer.

Molecular Heterogeneity of Cervical Cancer Among Different Ethnic/Racial Populations

The study aimed to find differential gene mutation profile and gene expression status among different ethnic/racial human populations relevant for cervical cancer pathogenesis. The study was based on freely available datasets of The Cancer Genome Atlas (TCGA) of cervical cancer samples in Genomic Data Commons (GDC) data portal. We identified that choline metabolism in cancer and Ras signaling pathways were significantly associated with the Hispanic and Latino group of cervical cancer patients. In these pathways, mutations in the PIK3CA gene, especially E545K, were significantly associated with the Hispanic and LATINO group. We found that AFF3 gene mutation was associated with downregulation of its expression only among the White racial category of cervical cancer cases. Additionally, hypomethylation of the CpG position in the S shore region of the PM20D1 gene was associated with overexpression among the Asian category of cervical cancer cases. Heterogeneity of the molecular profile of AFF3 and PM20D1 gene among racial groups reflects the potential of differential targeted therapy of cervical cancer.

Identification of novel genetic and epigenetic regulators of different tissue types of cervical cancer

AbstractObjectivesThe study aimed to find differential gene mutations, DNA methylation, and expression profiles among different categories of cervical cancer samples.MethodsThe study was based on freely available gene mutations, promoter methylation, and gene expression status of The Cancer Genome Atlas (TCGA) cervical cancer samples and adjacent normal tissues in the Genomic Data Commons (GDC) portal. The association of CpG island methylation with gene expression was determined through negative correlation analysis.ResultsWe identified that the ErbB signaling pathway and proteoglycans pathway was significantly associated with adenocarcinoma cervical cancers patients. In these pathways, missense mutation especially S310F in theERBB2gene as well as G12D and A146T in theKRASgene were significantly associated with adenocarcinoma cases. Furthermore, a comparison of SCC cases with adjacent control tissues revealed differential hypermethylation of two CpG positions of theKAAG1gene and differential downregulation ofNPY1RandNPY5Rgenes in cervical squamous cell carcinoma compared to cervical adenocarcinoma cases and adjacent normal tissues. Specifically, the hypermethylation of the promoter region of theKAAG1gene might be responsible for the carcinogenesis of cervical squamous cells exclusively and methylation marks can be reversible by the widely used drug, azacytidine. In contrast, adenocarcinoma cervical cancer cases may be treated with floxuridine which is successfully utilized for other tissue‐specific adenocarcinoma cases.ConclusionsThese results provide valuable insight into the differential molecular markers among the categories of cervical cancer, which helps our ability to classify these cancers and for targeted therapy.