Dataset Information

Human papillomavirus 16 infection in adenocarcinoma of the cervix.

ABSTRACT: The impact of the success of organised cervical screening programme results in a steady decline of the incidence of squamous cell carcinoma of the cervix but a concomitant increase in the incidence of the less common histological subtypes, particularly adenocarcinoma of the cervix (ACC). Although Human papillomavirus (HPV) infection is believed to be a necessary cause of cervical cancer, its role in the pathogenesis of ACC is not well established. Established associations between oncogenic strains of HPV and ACC are based on molecular studies carried out on entire tumour block sections. In this study, the cervical adenocarcinoma cells of a 10-year cohort of women diagnosed with ACC were dissected using the PixCell II Laser Microdissecting System to detect the HPV 16 genome sequence using the real-time quantitative polymerase chain reaction to confirm the presence of HPV DNA within ACC cells. By coupling these two sophisticated techniques, the HPV DNA copy number cell could be calculated to investigate its role. The prevalence of HPV 16 infection in this cohort was 24%, which is significantly higher than the control group (chi(2), P=0.014). Women with ACC also had significantly higher HPV DNA copy number per cell compared to the control group (P=0.00007). Higher HPV DNA copy number is associated with risk of developing ACC.

SUBMITTER: Chew GK

PROVIDER: S-EPMC2361519 | biostudies-other | 2005 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:Human papillomavirus (HPV) infection is the world's most common sexually transmitted infection and is responsible for most cases of cervical cancer. Previous studies of global gene expression changes induced by HPV infection have focused on the cancerous stages of infection, and therefore, not much is known about global gene expression changes at early preneoplastic stages of infection. We show for the first time the global gene expression changes during early-stage HPV16 infection in cervical tissue using 3-dimensional organotypic raft cultures, which produce high levels of progeny virions. cDNA microarray analysis showed that a total of 594 genes were upregulated and 651 genes were downregulated at least 1.5-fold with HPV16 infection. Gene ontology analysis showed that biological processes including cell cycle progression and DNA metabolism were upregulated, while skin development, immune response, and cell death were downregulated with HPV16 infection in cervical keratinocytes. Individual genes were selected for validation at the transcriptional and translational levels, including UBC, which was central to the protein association network of immune response genes, and top downregulated genes RPTN, SERPINB4, KRT23, and KLK8 In particular, KLK8 and SERPINB4 were shown to be upregulated in cancer, which contrasts with the gene regulation during the productive replication stage. Organotypic raft cultures, which allow full progression of the HPV life cycle, allowed us to identify novel gene modulations and potential therapeutic targets of early-stage HPV infection in cervical tissue. Additionally, our results suggest that early-stage productive infection and cancerous stages of infection are distinct disease states expressing different host transcriptomes.IMPORTANCE Persistent HPV infection is responsible for most cases of cervical cancer. The transition from precancerous to cancerous stages of HPV infection is marked by a significant reduction in virus production. Most global gene expression studies of HPV infection have focused on the cancerous stages. Therefore, little is known about global gene expression changes at precancerous stages. For the first time, we measured global gene expression changes at the precancerous stages of HPV16 infection in human cervical tissue producing high levels of virus. We identified a group of genes that are typically overexpressed in cancerous stages to be significantly downregulated at the precancerous stage. Moreover, we identified significantly modulated genes that have not yet been studied in the context of HPV infection. Studying the role of these genes in HPV infection will help us understand what drives the transition from precancerous to cancerous stages and may lead to the development of new therapeutic targets.

Dataset Information

Human papillomavirus 16 infection in adenocarcinoma of the cervix.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure