C. Meg McLachlin

Prognostic value of microsatellite instability (MSI) and PTEN expression in women with endometrial cancer: Results from studies of the NCIC Clinical Trials Group (NCIC CTG)

AIM The impact of PTEN status and microsatellite instability (MSI) on the prognosis of women with endometrial cancer is controversial. The aim of this study was to investigate MSI and PTEN expression in two patient populations using data from NCIC CTG studies. METHODS Archival paraffin embedded tumour from women with endometrial cancer enrolled in NCIC CTG studies: EN5 (stage I/II) and IND 126, 148 and 160 (advanced/recurrent disease) were examined for MSI using BAT25/26 and for PTEN expression using immunohistochemistry. PTEN and MSI status were correlated with clinicopathologic variables and survival using data from NCIC CTG trial databases. RESULTS PTEN and MSI results were available from 128 and 163 patients, respectively. MSI+ tumours were more common in women enrolled in EN5 compared to the IND studies (p=0.01). PTEN negative tumours were associated with improved survival in both univariate (hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.32-0.94; p=0.03) and multivariate (adjusted HR 0.54, 95% CI 0.30-0.96; p=0.03) analyses in women enrolled in IND studies. Microsatellite stable tumours were associated with an improved prognosis in univariate (HR 0.18, 95% CI 0.06-0.51; p<0.0001) and multivariate (adjusted HR 0.16, 95% CI 0.05-0.5; p<0.0001) analyses in women enrolled in EN5. There was no significant correlation between MSI and PTEN status. CONCLUSIONS PTEN negative tumours in women with advanced disease are associated with improved survival. MSI+ tumours are more common in early stage disease and in this group of women are associated with a worse prognosis.

Cervical Screening: A Guideline for Clinical Practice in Ontario

OBJECTIVE To develop guidelines to inform the Ontario Cervical Screening Programs invitations to women in the target population, provide evidence-based clinical practice guidance for practitioners, and inform policy decisions. METHODS A systematic review was conducted of relevant websites, the Medline and EMBASE databases (2005 to November 2010), and the Cochrane Library (2005 to 2010). No guidelines or systematic reviews were located that addressed the topics of interest. The evidence base consisted of seven randomized controlled trials, three case-control studies, one cohort study, and one review article. A methodologist performed data identification and extraction. Review of the data and quality assessment was carried out by the authors, who have expertise in methodology, gynaecologic oncology, pathology, and family medicine. The systematic review methods and resulting recommendations were reviewed by an internal panel with clinical, methodological, and oncology expertise. External review was provided by Ontario clinicians and other experts. CONCLUSIONS The guideline development process led to recommendations for the optimal primary cervical screening method, screening interval, and age of screening cessation for Ontario women in the target population. There was insufficient evidence to provide a recommendation for age of initiation of cervical screening with HPV testing. The creation of an organized screening program in the province will allow the implementation of evidence-based recommendations. We provide interim recommendations for cervical screening until HPV testing has been funded.

HPV Testing in Primary Cervical Screening: A Systematic Review and Meta-Analysis

OBJECTIVE Previous findings from cross-sectional studies have shown human papillomavirus (HPV) testing to be more sensitive than cytology testing for primary cervical screening. This systematic review aims to assess whether the increase in baseline detection with HPV testing corresponds to lower rates in subsequent screening rounds. METHODS We searched Medline, EMBASE, and the Cochrane Library for randomized controlled trials (published from 2005 to 2010) comparing HPV-based and cytology-based cervical screening. Primary outcomes of interest were relative rates of higher grade cervical intraepithelial neoplasia and invasive cervical cancer. Secondary outcomes included test performance characteristics and colposcopy referral rates. Results were pooled where possible using a random effects model. RESULTS Seven randomized trials were identified. Across studies, HPV testing was more accurate than conventional cytology and detected significantly more CIN3+ in the first screening round (Mantel-Haenszel [M-H] risk ratio 1.67; 95% CI 1.27 to 2.19) and significantly less in the second screening round (M-H RR 0.49; 95% CI 0.37 to 0.66). There were no differences in pooled rates of CIN2+ (M-H RR 1.19; 95% CI 0.94 to 1.50) and CIN3+ (M-H RR 1.09; 95% CI 0.84 to 1.42), but there was a higher pooled rate of CIN2 (M-H RR 1.37; 95% CI 1.12 to 1.68) over two screening rounds. A trend towards lower rates of invasive cervical cancer was observed. CONCLUSION Organized screening programs in higher resource settings should consider adopting HPV testing as the primary screening test for women 30 or 35 years of age and older. Further research is needed to determine optimal screening strategies for younger women.

Comparison of ThinPrep and conventional smears in salivary gland fine-needle aspiration biopsies.

ThinPrep (TP) cytology for evaluation of nongynecological specimens is being increasingly used. There are few studies comparing TP with conventional smears (CS) in salivary gland (SG) fine‐needle aspiration biopsies (FNAB). This study compares diagnostic accuracy and morphology of TP and CS in SG FNABs.

Report of the 2003 Pan-Canadian Forum on Cervical Cancer Prevention and Control: The recommendations reported herein reflect the decisions of the pan-Canadian forum participants as individual experts and do not necessarily reflect official policies of their respective organizations.

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 womens 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.

Ontario Cervical Cancer Screening Clinical Practice Guidelines

OBJECTIVE To develop clinical practice guidelines for cervical screening and the primary management of abnormal cytology in Ontario, using an established methodological process. DATA SOURCES Primary data sources were relevant articles listed in the Medline (1998 to July 2004), Embase (1998 to July 2004), and Cochrane Library (2004, Issue 2) databases. STUDY SELECTION Studies addressing quality or the optimization of cervical screening were considered eligible in the systematic review of the evidence. Specifically, clinical practice guidelines, technology assessments, systematic reviews, and randomized controlled trials were of primary interest. Given the variability of the data, other information sources were considered eligible if there was a demonstrated gap in the published literature. DATA EXTRACTION Data were identified and extracted by a methodologist and reviewed by four authors. Results were reviewed and discussed by members of an expert working group consisting of a diverse group of health professionals with expertise in cervical cancer. Data audits were conducted by independent reviewers. DATA SYNTHESIS recommendations with evidence ratings were developed through a review of the evidence with expert consensus and were approved by more than 80% of 40 external practitioners who reviewed the document and responded to a standardized survey. CONCLUSION The development of comprehensive recommendations on cervical screening in Ontario was feasible using a rigorous methodological process. Recommendations for practice are provided.

A validation study of the FocalPoint GS imaging system for gynecologic cytology screening.

Studies of the performance of the automated FocalPoint Guided Screening (FPGS) imaging system in gynecologic cytology screening relative to manual screening have yielded conflicting results. In view of this uncertainty, a validation study of the FPGS was conducted before its potential adoption in 2 large laboratories in Ontario.

The optimum organization for the delivery of colposcopy service in Ontario: a systematic review.

Objective: To determine the optimum organization for colposcopy service delivery in Ontario, Canada. Methods: A multidisciplinary expert panel was convened to develop a systematic review to inform organizational guidelines. MEDLINE, EMBASE, CINAHL, HealthSTAR, and the Cochrane Library databases were searched from 1996 to February 2006 for articles that reported guidance or outcomes relating to improved outcomes in colposcopy training, qualifications, accreditation, maintenance of competency, the delivery of colposcopy, reducing default from colposcopy clinics, and/or strategies to improve patient satisfaction or comfort. In addition, an environmental scan identified unpublished documents related to the delivery of colposcopy services. Results: Sixteen guidance documents related to the delivery of colposcopy services were identified; 5 from the published literature and 11 from the environmental scan. These documents were used by the panel to inform the systematic review and companion guidelines. Conclusions: Overall, the Ontario Colposcopy Guidelines Development Group believes that the benefits associated with the implementation of colposcopy recommendations in Ontario will result in greater organization of care and improved patient outcomes. In addition, the group anticipates that these recommendations will provide useful guidance to regional planning authorities, hospital administrators, and Cancer Care Ontario, as well as colposcopists and other practitioners, in the planning of integrated regional and provincial cancer screening services.

Performance measures related to colposcopy for canadian cervical cancer screening programs: identifying areas for improvement.

OBJECTIVE To describe performance measures related to colposcopic examinations in Canadian cervical cancer screening programs; specifically, time to colposcopy, histological investigation rate, and agreement between cytology and histology. METHODS As part of a national report on the performance of cervical cancer screening, aggregate provincial cervical cancer screening data provided by provinces to the Pan-Canadian Cervical Screening Network were used to evaluate colposcopy program performance measures for women 20 to 69 years of age who had a Pap test in 2009 and 2010. RESULTS A total of 37 523 women had a high-grade or more severe Pap test result. The proportion of women who had a colposcopy ≤ 90 days after their Pap test ranged from 30.9% to 51.5%. Fewer women 60 to 69 years of age had a colposcopy than women in younger age groups. The proportion of women who had a high-grade or more severe Pap test result and colposcopy who had a biopsy within 12 months ranged from 82.1% to 96.5%. The proportion of biopsy results that agreed with the Pap test result ranged from 59.5% to 82.1%. CONCLUSION The time from having a high-grade Pap test result to undergoing colposcopy must be reduced to lower the risk of adverse outcomes and the stress associated with delayed follow-up. The agreement between screening cytology and histology meets the national target of ≥ 65%. Although six of 13 provinces and territories provided data for colposcopy-related performance measures, more information is needed to assess colposcopy services accurately at the national level.