Report of the 2003 pan-Canadian forum on cervical cancer prevention and control.

OBJECTIVE: To develop evidence-based consensus recommendations on the delivery of cervical cancer screening, human papillomavirus (HPV) education, HPV testing, and the optimal tool for cervical cytology within the Canadian health system. PARTICIPANTS: Leading up to a forum held in Ottawa on November 21 and 22, 2003, 254 registrants reviewed position papers through a Web-based discussion group. Experts in program management, clinical practice, epidemiology, public health, economics, and women's health, representing 48 organizations, then participated in the 2-day forum to develop consensus recommendations. EVIDENCE: Writing groups prepared position papers on optimal methods for cervical cytology; education concerning HPV; HPV testing in primary screening; HPV testing as a triage tool in cytopathology; and delivery mechanisms for cervical screening. Systematic reviews were the primary source of evidence supplemented by literature searches. CONSENSUS PROCESS: Feedback from Web-based discussions was incorporated into consecutive drafts of position papers. At the forum, recommendations and supporting evidence were presented, further debated in small-group sessions, and discussed in a plenary session. Despite divergent professional mandates and opinions, consensus was achieved on 15 recommendations across all areas. Final recommendations were posted to the Web for further input and circulated for written consensus by participants. CONCLUSIONS: The recommendations cover the use of new evidence and technologies in cervical cancer prevention in Canada and provide a framework for provision of HPV education, planning the implementation of new cervical screening technologies in Canada, the development of evaluation plans, and new research areas.

A comparative analysis of gene expression patterns and cell phenotypes between cervical and peripheral blood mononuclear cells.

Studies of the immunological environment in the female genital tract (FGT) are critical for the development of vaccines or microbicides to halt the spread of sexually transmitted infections. Challenges arise due to the difficulties of sampling from this site, and the majority of studies have been conducted utilising peripheral blood mononuclear cells. Identifying functional differences between immune cells of the FGT and peripheral blood would aid in our understanding of mucosal immunology. We compared the gene expression profile of mononuclear cells at these two sites. Messenger RNA expression analysis was performed using gene expression arrays on matched cervical mononuclear cells and peripheral blood mononuclear cells. Further cellular phenotyping was done by 10 colour flow cytometry. Of the 22,185 genes expressed by these samples, 5345 genes were significantly differentially expressed between the cell populations. Most differences can be explained by significantly lower levels of T and B cells and higher levels of macrophages and dendritic cells in the FGT compared with peripheral blood. Several immunologically relevant pathways such as apoptosis and innate immune signalling, and a variety of cytokines and cytokine receptors were differentially expressed. This study highlights the importance of the unique immunological environment of the FGT and identifies important differences between systemic and mucosal immune compartments.

Premalignant cervical lesions are characterized by dihydrofolate reductase gene amplification and c-Myc overexpression: possible biomarkers.

OBJECTIVE: The c-Myc oncoprotein deregulation is associated with overall genomic instability and locus-specific genomic instability involving the dihydrofolate reductase (DHFR) locus. This study analyzes c-Myc protein levels and the stability of the DHFR gene in cervical tissue biopsies. MATERIALS AND METHODS: The stability of the DHFR gene was examined by fluorescence in situ hybridization (FISH). c-Myc protein levels were evaluated using quantitative fluorescent immunohistochemistry. Forty-four cervical tissue biopsies were analyzed and included 33 preinvasive cervical lesions identified by histology, 14 samples were cervical intraepithelial neoplasia (CIN) 1; 7 were CIN 2; and 12 were CIN 3. Eleven biopsies had negative histology. RESULTS AND CONCLUSION: c-Myc protein levels were elevated in CIN 1, 2, and 3 (p = .02) biopsies. Concomitantly, DHFR gene amplification was detected in CIN 1, 2, and 3 (p = .0001). The degrees of DHFR gene amplification and of c-Myc protein levels were a measure of the progressive degree of the lesion.