Jill Tinmouth

The role of cytology (Pap tests) and human papillomavirus testing in anal cancer screening.

Objective:To assess anal oncogenic human papillomavirus (HPV) and anal cytology as screening tests for detecting high-grade anal intraepithelial neoplasia (AIN 2+), as this is an immediate anal cancer precursor. Design:Cross-sectional study of 401 HIV-positive men who have sex with men (MSM). The endpoint was histologically confirmed AIN 2+ obtained by high-resolution anoscopy. Cytology and biopsy specimens were assigned random numbers and independently assessed by two pathologists. Methods:We did concomitant anal cytology, anal HPV testing and HRA with directed biopsies without knowing the results of each intervention. The main outcome measures were the sensitivity, specificity, negative predictive value and positive predictive value of anal cytology and oncogenic HPV for the detection of AIN 2+. Results:Cytology was abnormal in 67% of patients: high-grade squamous intraepithelial lesion, 12%; low-grade squamous intraepithelial lesion, 43% and atypical squamous cells of undetermined significance, 12%. Biopsies were abnormal in 68% of patients: AIN 2+, 25% and AIN 1, 43%. HPV was detected in 93% with multiple HPV types in 92% and oncogenic HPV types in 88%. Test performance characteristics for the detection of AIN 2+ using any abnormality on anal cytology were: sensitivity 84%, specificity 39%, negative predictive value 88% and positive predictive value 31%; using oncogenic HPV: sensitivity 100%, specificity 16%, negative predictive value 100% and positive predictive value 28%. Conclusion:Anal cytology and HPV detection have high sensitivity but low specificity for detecting AIN 2+. HIV-positive men who have sex with men have a high prevalence of AIN 2+ and require high-resolution anoscopy for optimal detection of high-grade anal dysplasia.

Cost-effectiveness of screening for anal precancers in HIV-positive men.

Objective:To assess the cost-effectiveness of high-resolution anoscopy (HRA), anal cytology, and anal human papillomavirus (HPV) detection in screening for histologic high-grade anal intraepithelial neoplasia (AIN 2/3) in HIV-positive MSM. Design:Participants were 401 HIV-positive MSM who were screened for anal cancer in a tertiary care HIV clinic. Methods:A decision analytical model was used to determine the cost-effectiveness of three anal cancer screening strategies: the direct use of HRA; HRA only if anal cytology was abnormal; and HRA only if oncogenic HPV was present. The model included the use of different thresholds for abnormal cytology and also combined cytology and HPV testing. The outcome was the number of AIN 2/3 cases detected. Costs were estimated from institutional data and sensitivity/specificity of cytology and HPV tests were obtained from the screening study. Results:The costs (

Screening for HIV-Associated Anal Cancer: Correlation of HPV Genotypes, p16, and E6 Transcripts with Anal Pathology

US) per procedure for HRA, cytology, and HPV testing were

Impact of Clostridium difficile colitis on 5-year health outcomes in patients with ulcerative colitis.

193,

A Population-based Analysis of Outpatient Colonoscopy in Adults Assisted by an Anesthesiologist

90, and

Disparities in Receipt of Screening Tests for Cancer, Diabetes and High Cholesterol in Ontario, Canada: A Population-based Study Using Area-based Methods

95, respectively. The direct use of HRA was the most cost-effective strategy. It detected 98 individuals with AIN 2/3 and had a cost-effectiveness of

Sessile Serrated Polyps at Screening Colonoscopy: Have They Been Under Diagnosed?

809 per AIN 2/3 case detected. Using probabilistic sensitivity analysis, three other strategies had similar costs per case detected and might be as cost-effective as HRA. Conclusion:In HIV-infected MSM, the direct use of HRA is the most cost-effective strategy for detecting AIN 2/3. The higher cost per use for HRA was offset by the high sensitivity and low specificity of HPV and cytology testing.

Benefit of transplantation in primary biliary cirrhosis between 1985-1997.

Background: HIV-positive men with a history of anal-receptive intercourse are at risk for anal cancer. We determined whether human papilloma virus (HPV) biomarkers were correlated with anal pathology in these men. Methods: HPV genotype was determined by PCR/line blot assay. Real-time PCR assays were done for viral load, E6 transcripts for HPV genotypes 16, 18, and 31, and p16 transcripts. Results: The most common oncogenic HPV types were HPV 16 (38%), 18 (19%), 45 (22%), and 52 (19%). HPV types 16, 18, 31, 52, 59, and 68 were associated with high-grade histology. The number of HPV genotypes per anal swab was higher for anal intraepithelial neoplasia (AIN) 2/3 than for normal or AIN 1 histology [median, 5 types (interquartile range) (IQR), 3-7 versus 3.5 (IQR), 2-6; P = 0.0005]. HPV 16 viral load was also associated with AIN 2/3 histology. There was no difference in p16 or E6 transcripts between histologic grades. In the multivariable logistic regression model, HPV genotypes 16 [odds ratio, 2.58; 95% confidence interval (95% CI), 1.31-5.08; P = 0.006] and 31 (odds ratio, 4.74; 95% CI, 2.00-11.22; P = 0.0004), baseline CD4 count < 400 cells/mm3 (odds ratio, 2.96; 95% CI, 1.46-5.99; P = 0.0025), and Acquired Immunodeficiency Syndrome (AIDS)-defining illness (odds ratio, 2.42; 95% CI, 1.22-4.82; P = 0.01) were associated with high-grade histology after adjusting for age. Conclusions: The presence of high-grade anal pathology (AIN 2/3) in HIV-positive men was associated with multiple HPV genotypes, HPV genotypes 16 and 31, and HPV 16 viral load. (Cancer Epidemiol Biomarkers Prev 2009;18(7):1986–92)

Ontario's ColonCancerCheck: Results from Canada's First Province-Wide Colorectal Cancer Screening Program

Clostridium difficile colitis (CDC) is associated with an increased short‐term mortality risk in hospitalised ulcerative colitis (UC) patients. We sought to determine whether CDC also impacts long‐term risks of adverse health events in this population.

Presumed previous human papillomavirus (HPV) related gynecological cancer in women diagnosed with anal cancer in the province of Ontario.

Background:The use of propofol to sedate patients for colonoscopy, generally administered by an anesthesiologist in North America, is increasingly popular. In the United States, regional use of anesthesiologist-assisted endoscopy appears to correlate with local payor policy. This study’s objective was to identify nonpayor factors (patient, physician, institution) associated with anesthesiologist assistance at colonoscopy. Methods:The authors performed a population-based cross-sectional analysis using Ontario health administrative data, 1993–2005. All outpatient colonoscopies performed on adults were identified. Hierarchical multivariable modeling was used to identify patient (age, sex, income quintile, comorbidity), physician (specialty, colonoscopy volume), and institution (type, volume) factors associated with receipt of anesthesiologist-assisted colonoscopy. Results:During the study period, 1,838,879 colonoscopies were performed on 1,202,548 patients. The proportion of anesthesiologist-assisted colonoscopies rose from 8.4% in 1993 to 19.1% in 2005 (P < 0.0001). In the hierarchical model, patients in low-volume community hospitals were five times more likely to receive anesthesiologist-assisted colonoscopy than patients in high-volume community hospitals (odds ration 4.9; 95% confidence interval 4.4–5.5). Less than 1% of colonoscopies in academic hospitals were anesthesiologist-assisted. Compared to gastroenterologists, surgeons were more likely to perform anesthesiologist-associated colonoscopy (odds ratio 1.7; 95% confidence interval 1.1–2.6). Conclusions:In Ontario, rates of anesthesiologist-assisted colonoscopy have risen dramatically. Institution type was most strongly associated with this practice. Further investigation is needed to determine the most appropriate criteria for the use of anesthesiology services during colonoscopy.