Case-control study of lifetime total physical activity and prostate cancer risk.

A population-based case-control study of physical activity and prostate cancer risk was conducted in Alberta, Canada, between 1997 and 2000. A total of 988 incident, histologically confirmed cases of stage T2 or greater prostate cancer were frequency matched to 1,063 population controls. The Lifetime Total Physical Activity Questionnaire was used to measure occupational, household, and recreational activity levels from childhood until diagnosis. Multivariable logistic regression analyses were conducted. No association for total lifetime physical activity and prostate cancer risk was found (odds ratio (OR) for > or =203 vs. <115 metabolic equivalent-hours/week/year=0.87, 95% confidence interval (CI): 0.65, 1.17). By type of activity, the risks were decreased for occupational (OR=0.90, 95% CI: 0.66, 1.22) and recreational (OR=0.80, 95% CI: 0.61, 1.05) activity but were increased for household (OR=1.36, 95% CI: 1.05, 1.76) activity when comparing the highest and lowest quartiles. For activity performed at different age periods throughout life, activity done during the first 18 years of life (OR=0.78, 95% CI: 0.59, 1.04) decreased risk. When activity was examined by intensity of activity (i.e., low, <3; moderate, 3-6; and vigorous, >6 metabolic equivalents), vigorous activity decreased prostate cancer risk (OR=0.70, 95% CI: 0.54, 0.92). This study provides inconsistent evidence for the association between physical activity and prostate cancer risk.

The natural history of CIN I lesions.

The published literature indicates 11% of CIN I lesions on average progress to a higher grade dysplasia and the remainder either regress or persist. Reliable markers of disease outcome are yet to be identified. A longitudinal study of 342 women referred for colposcopic examination of a CIN I detected by a screening Pap test, and classified by the colposcopic impression and Pap test at that exam as

Predictors of co-incidental CIN II/III amongst a cohort of women with CIN I detected by a screening Pap test.

Approximately 20-40% of lesions interpreted by a screening Pap test as CIN I and subsequently examined by colposcopy include a co-incidental CIN II/III. Since the HPV profiles of CIN I and CIN II/III differ, HPV typing may predict these co-incidental higher grade lesions. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of CIN I as classified by a screening Pap test were triaged into group A (/= CIN II). Clinical, demographic, reproductive, and risk factor data was collected by questionnaire and HPV typing of cervical scrapes was done by PCR. Group A included 342 (63.7%) women and group B 195 (36.3%). Group B women more frequently were current cigarette smokers (p<0.001) and had a high school or lesser level of education (p=0.04). HPV positivity amongst younger group B women (

Review of the screening history of Alberta women with invasive cervical cancer.

OBJECTIVE: To conduct a failure analysis of cervical cancer screening among women with invasive cervical cancer in Alberta. DESIGN: Descriptive study. Review of demographic, staging and treatment information from cancer registry records; generation of documented screening history from Alberta Health billing records and self-reported history from subjects who agreed to be interviewed; and comparison of findings in initial cytology reports with those from subsequent review by at least 2 pathologists of all cytology slides for each patient for the 5 years before diagnosis. Cases were assigned to 1 of 6 categories of identified screening failure. SETTING: Alberta. SUBJECTS: All women with diagnosis of invasive cervical cancer reported to a population-based provincial cancer registry from January 1990 to December 1991. OUTCOME MEASURES: Demographic, staging and treatment information; documented and self-reported screening histories; correlation of test results in initial cytology report with those generated from slide review; category of identified screening failure. RESULTS: Of the 246 women identified with invasive cancer of the cervix, 37 (15.0%) had stage IA disease; 195 (79.3%) had squamous-cell carcinoma, and 35 (14.2%) had adenocarcinoma. According to the categories of screening failure, 74 women (30.1%) had never been screened, 38 (15.4% had not been screened within 3 years before diagnosis, 42 (17.1%) had had a false-negative cytology result, and 20 (8.1%) had been managed outside of conventional protocols. Of the 23 women (9.3%) who had been screened appropriately and had true-negative results, 19 had smears that were considered technically limited. It was not possible to classify 49 (19.9%) of the cases. Agreement between the documented and the self-reported screening histories was exact for only 39 (36.1%) of the 108 women interviewed. CONCLUSIONS: Despite widespread use of opportunistic cervical screening, many women in Alberta are still not being screened adequately. In most cases women are being screened too infrequently or not at all. Self-reported screening histories are unreliable because many women may overestimate the number of smears. An organized approach to screening, as recommended by the National Workshop in Cervical Cancer Screening, may assist in reducing the incidence of invasive cervical cancer.

The HPV determinants of CIN I.

Correlates of HPV amongst a cohort of women with a CIN I detected by a screening Pap test were investigated. Co-incident CIN II/III lesions were identified and their influence on the HPV status and HPV determinants of screening detected CIN I was assessed. Based on both the colposcopic impression and repeat Pap test, 537 women referred for examination of a Pap test classified as CIN I were triaged into two groups. Group A lesions were assessed as /= CIN II; n = 195 (36.3%). Clinical, demographic, reproductive, and risk factor for cervical cancer correlates were collected. HPV typing of cervical scrapes collected at the colposcopic examination was done by PCR amplification using seven sets of type specific and one set of consensus primers. HPV positivity was identified in 47% of all scrapes; types 16/18 (28%), 31/33/35 (10%), 6/11 (2%), and unknown (7%). The HPV status of the cohort and group A were very similar. Group B had a slightly higher rate of HPV positivity (52%) due to an increase in types 16/18. Statistically significant correlates of HPV prevalence or type were not identified either for the entire group or both triage groups, however in each group, HPV positive women tended to be younger and to have more sexual partners. Co-incident CIN II/III spuriously increased the HPV prevalence rate of CIN I detected by a screening Pap test. The HPV appears to be sexually transmitted both in low and high grade lesions and explains why the HPV determinants of the entire cohort were unaffected by the co-incident CIN II/III.

The human papillomavirus status of invasive cervical adenocarcinoma: a clinicopathological and outcome analysis.

Accumulating evidence highlights the human papillomavirus (HPV) as a risk factor for cervical adenocarcinoma. However, the part played by the HPV in predicting tumor outcome or the increasing frequency of cervical adenocarcinoma is incompletely studied. In a retrospective study the association between HPV status and the clinicopathological characteristics of 77 cases of cervical adenocarcinoma was investigated. The data were then analyzed for temporal differences in HPV status and to identify outcome predictors. Human papillomavirus status was determined by dot blot hybridization using probes for HPV 6, 11, 16, 18, 31, 33, and 35, followed by polymerase chain reaction amplification of the dot blot negative cases. Seven type-specific and consensus HPV primers were used. Human papillomavirus type 16, 18, or 33 was present in 53 (70%) cases. Human papillomavirus status did not correlate with disease outcome or any clinicopathological variable, except that tumors presenting in and after 1981 were more frequently HPV positive than those presenting before 1981 (P = .014). In a multivariate analysis only clinical stage at presentation was predictive of disease outcome. Because temporal differences in clinicopathological characteristics were not identified, the increasing frequency of cervical adenocarcinoma may relate to a more important oncogenic role for the HPV in tumors presenting after 1980.

Adenocarcinoma in situ of the endocervix: human papillomavirus determination by dot blot hybridization and polymerase chain reaction amplification.

The frequency of human papillomavirus (HPV) in series of endocervical adenocarcinoma in situ (AIS) ranges from 6 to 100%. Some of this variability can be attributed to small study numbers and such technical considerations as the sensitivity of the hybridization method employed. Consequently, the role of the HPV in AIS oncogenesis is unclear. The frequency and relative distribution of HPV DNA types 6, 11, 16, 18, 31, 33, and 35 in 37 cases of AIS were determined and correlated with clinical variables. All cases were first typed by dot blot hybridization (DBH), and those found to be HPV negative were subsequently typed by polymerase chain reaction amplification with DBH enhancement (PCR/DBH). The HPV DNA positivity rate was 27% by DBH alone and 52% by PCR/DBH amplification. Combining the results of both methods, the overall HPV positivity rate was 66%: HPV 18 in 15 cases (43%), HPV 16 in eight cases (23%). The HPV status did not correlate with any clinical variable. This study showed that the sensitivity of the hybridization method is principally accountable for the variable frequency of HPV in AIS. The identification of only high-risk oncogenic HPV types in two-thirds of the cases suggests a significant role for the virus in AIS oncogenesis; HPV status, however, does not delineate a clinical profile.

A paired comparison of dot blot hybridization and PCR amplification for HPV testing of cervical scrapes interpreted as CIN 1.

The rate of Human Papillomavirus (HPV) detection in CIN 1 lesions is quite variable for several reasons. Amongst these, the sensitivity level of the HPV detection system probably ranks supreme. The prevalence of HPV DNA in cervical scrape samples from 234 patients referred for colposcopic investigation of a CIN 1 lesion was compared using dot blot hybridization (DBH) and polymerase chain reaction (PCR) amplification. Both methods were performed on the same patient sample so that determinants of HPV positivity other than the detection system could be controlled. Probes and primers to HPV 6, 11, 16, 18, 31, 33, and 35, and consensus HPV primers were used. The overall HPV positivity rate was 24% using DBH and 70% using PCR. Identified types by DBH and PCR respectively were; HPV 6/11: 1% and 2%, HPV 16/18: 16% and 41%, and HPV 31/33/35: 7% and 14%. PCR detected unidentified types in 13%. Since PCR resulted in a 2.9 times higher HPV DNA detection rate, the choice of detection system has a major impact on the HPV status of cervical smears interpreted as CIN 1.

The human papillomavirus status of 114 endocervical adenocarcinoma cases by dot blot hybridization.

The reported rate of human papillomavirus (HPV) positivity in cases of endocervical adenocarcinoma averages 38% (range, 0% to 100%) and, in contrast to cervical squamous cell carcinoma, HPV type 18 rather than type 16 is the predominant type. The HPV positivity rate and distribution of types (status) in 114 endocervical adenocarcinoma cases (37 in situ and 77 invasive) were determined by dot blot hybridization using biotinylated probes to HPV types 6, 11, 16, 18, 31, 33, and 35. Human papillomavirus DNA was present in 27% of in situ and in 44% of invasive adenocarcinomas, and in nearly all histologic subtypes of invasive adenocarcinoma. Human papillomavirus status was not predictive of tumor grade, volume, depth of invasion, lymph-vascular space involvement, age at presentation, or year of diagnosis. Type of HPV might influence the histologic subtype of invasive adenocarcinoma, as HPV type 16 predominated in the adenosquamous carcinomas while HPV type 18 was more frequently found in all other subtypes. Since only types 16, 18, and 33 were identified, an oncogenic role for HPV in endocervical carcinogenesis was supported.

Age is prognostic variable in cervical squamous cell carcinoma.

A clinico-pathologic review was performed on all younger (under 35 years) and older (55 years or over) women with a diagnosis of cervical squamous cell carcinoma assessed at the Tom Baker Cancer Centre from 1980 to 1985 to determine the effect of age at diagnosis on survival. 45 younger women were identified: 32 were Stage IB; 10, Stage II; and 3, Stage III. 64 older women were identified: 16 were Stage IB; 30, Stage II; 14, Stage III; and 4, Stage IV. For Stage IB women, 40.6% of younger patients developed persistent or recurrent disease and all except one are dead; only one (6.2%) older woman's tumour recurred and she is alive with disease. Younger women had a poorer disease-free survival not only for Stage IB disease (p = 0.014) but also in Stages II and III (p = 0.020). In this study age at diagnosis was an independent prognostic variable with younger women having a poorer disease-free and overall survival.

Attitudes about cancer and knowledge of cancer prevention among junior high students in Calgary, Alberta.

Results from a survey of junior high students conducted in preparation of curriculum materials on cancer prevention are reported. Students in the survey (n = 246) consider cancer to be a serious disease, not particularly amenable to treatment, and caused by many things. About half the students mentioned avoiding tobacco use as important in preventing cancer. However, 27% were unable to identify any ways to avoid getting cancer. Specific knowledge of dietary practices recommended to reduce cancer risk was poor, with fewer than 10% of students mentioning high fibre or low fat as important dietary habits. Knowledge of factors related to skin cancer was better, with 53% of students mentioning avoiding sun exposure as a way to reduce the risk of skin cancer. The majority of students (71%) wanted more information about cancer. The results from the survey indicate a need for cancer-prevention materials in the school curriculum.

Steve Fonyo Cancer Prevention Program: description of an innovative program.

The Steve Fonyo Cancer Prevention Program (SFCPP) was a demonstration project of community-based education strategies designed to increase behaviours which will result in reduced cancer deaths, and to assess the feasibility of the involvement of a provincial cancer agency in the delivery of community-based prevention programs. Using primarily two different strategies, the SFCPP attempted to influence people to choose healthy lifestyles which would reduce their risk of getting cancer and to practice those behaviours which would increase early detection. The health unit intervention component consisted of risk assessment, personalized feedback and an invitation to appropriate health education programs delivered by a nurse. The community-based component involved community members in the planning and delivery of cancer prevention programs. The program began in four small cities (combined population 165,000) in early 1987. A baseline survey was done prior to implementation to facilitate evaluation. The purpose of this article is to describe the planning and implementation of the Steve Fonyo Cancer Prevention Program.

A change in flushing protocols of central venous catheters.

Oncology nurses working with hematology patients at the Tom Baker Cancer Centre questioned the need for twice daily flushings of central venous catheters. The nurses speculated that weekly flushings would be more convenient for patients, maintain patency, reduce risk of infections, and save the costs of supplies and nursing time. In 1986, the nurses, in collaboration with physicians, introduced a weekly flushing protocol for outpatients attending the clinic. The staff noted that no difference in rates of infection or patency appeared to result from this change in protocol. In an effort to provide empirical data in support of this fundamental shift in nursing protocols, the nurses initiated a study to examine infection rates and patency related to weekly flushing procedures. The study involved 82 patients with 89 catheter insertions. Overall infection rates were 19.1% or 0.15 per 100 catheter days. These rates were 0.25 per 100 catheter days for patients undergoing bone marrow transplant (BMT) and 0.07 per 100 catheter days in patients not undergoing BMT. Reduced patency occurred in only 13.5% of catheters studied, requiring a change in flushing protocol. When compared with published complication rates, these findings support the use of a weekly flushing protocol. As a result, staff and patients continue to use the weekly flushing protocol with greater confidence.

Morphometric analysis of nucleolar organizer regions in benign and malignant peritoneal effusions using backscattered electron microscopy.

Nucleolar organizer regions are loops of DNA associated with silver-stainable proteins (AgNORs). In general, malignant cells have more and larger AgNORs than benign cells. An inconsistent argyrophilic method and difficulties in objectively evaluating AgNORs account for some of the reluctance to utilize AgNOR staining as a diagnostic tool to differentiate benign and malignant lesions. Sections from paraffin-embedded cell blocks of 10 cases of benign and malignant peritoneal effusions were stained with a modified AgNOR method. Backscattered electron imaging in the scanning electron microscope, together with image analysis, was used to evaluate more objectively a number of AgNOR parameters and to determine which measurement was the most reliable discriminant of the two types of fluids. One hundred nuclei per case were identified and imaged. In contrast to benign nuclei, AgNORs in malignant nuclei were more numerous (P less than 0.0001) and larger (P less than 0.0001). A cut-off mean AgNOR area of 1.1 microns 2 (P less than 0.0001) correctly categorized all malignant (greater than 1.1 microns 2) and benign (less than or equal to 1.1 micron 2) cases. This system's objectivity and specificity could be used to enhance the cytological interpretation of effusions, where the separation of reactive mesothelial cells and malignant cells is extremely difficult.

Fibroadenoma of the breast: diagnostic pitfalls of fine-needle aspiration.

On fine-needle aspiration (FNA), fibroadenomas have a characteristic cytological appearance, although occasional cases are misinterpreted as carcinomas and vice versa. In a review of 521 breast aspirates correlated with the subsequent histology, six of 87 fibroadenomas (7%) were malignant or suspicious of malignancy on FNA (false positives). Following cytological review, four were still suspicious of malignancy because of cellular dyscohesion and prominent nucleoli, while two were fibroadenomas. On FNA, four of 145 carcinomas (3%) were diagnosed as fibroadenomas (false negatives). On review, three were malignant or suspicious of malignancy, while one was consistent with a fibroadenoma. Three false negative diagnoses were due to underappreciation of single malignant cells present between epithelial groupings typical of a fibroadenoma, while one was due to undersampling of the carcinoma. Cytologically, some fibroadenomas are sufficiently atypical that histological confirmation is necessary to exclude a malignancy. Misinterpreting carcinomas as fibroadenomas could be avoided by careful study of the morphology of isolated cells.

Human papillomavirus DNA in anal carcinomas. Comparison of in situ and dot blot hybridization.

Because the sensitivities of individual hybridization techniques differ considerably, their role in accounting for the published frequencies of human papillomavirus (HPV) DNA in anal squamous cell carcinomas, ranging from 0 to 61%, must be investigated. With the use of biotinylated probes to HPV 6, 11, 16, 18, and 33, three hybridization techniques were performed on the same paraffin-embedded tissue blocks selected from 13 cases of anal squamous cell carcinoma. HPV DNA was detected in 0%, 62%, and 85% of cases with the use of in situ hybridization with horseradish peroxidase, in situ hybridization with alkaline phosphatase, and dot blot hybridization, respectively. By dot blot hybridization, 69% had HPV 16/6 and 15% had HPV 6/11. An HPV DNA frequency range of 0-85% in the same group of tumors with the use of three hybridization techniques indicates the influential role of the method on HPV DNA prevalences. HPV DNA was identified regardless of patient gender or type of squamous cell carcinoma. The presence of HPV 16 in 82% of the positive cases in supportive evidence of the carcinogenic role of the HPV in anal squamous cell carcinoma.

Cervico-vaginal screening in an STD clinic.

From May 1986 to March 1988, there were 3,622 "new" female clients at the Calgary Sexually Transmitted Disease (STD) Clinic of whom 2,278 registered for the first time. A cervico-vaginal (Pap) smear was obtained from those who had not had one in the previous 6 to 12 months and any history of venereal warts (VW) was recorded. 621 smears were accessed of which 611 were suitable for inclusion in this study. 65 (10.6%) smears revealed human papillomavirus (HPV) and/or cervical intraepithelial neoplasia (CIN). Any history of VW increased the likelihood of an abnormal smear by 5.3 times. Those with currently visible VW were more likely (8.8 times) to have an abnormal smear than those with a past history (3.5 times). These data re-affirm the recommendation of the first "Walton Report" that Pap smears should be obtained in STD Clinics.

A comparison of cervical scrapes for HPV typing by dot-blot hybridization obtained by wood and plastic spatulas.

A cross-over study was designed to determine whether the type of spatula used to collect cervical cells influences the ability of dot-blot hybridization to detect HPV DNA. Fifty-nine patients had a cervical scrape with a wood spatula first and a plastic spatula second: 60 were scraped in the inverse order. The order of sampling did not affect the HPV DNA positivity rate, which was nearly similar for both wood and plastic spatulas (30 and 32%, respectively). Wood spatulas collected more cells and greater than 1 x 10(5) cells more often than plastic spatulas (P = 0.001 and 0.06, respectively). Non-purple (negative) dots were more frequent in samples obtained by wood than by plastic spatulas (P = 0.001). The study showed that cervical cell collection by wood spatulas is preferred as they harvest more cells, thus optimizing the sensitivity of the hybridization method, and the spatulas are also more economical. Although they yielded more non-purple dots, a reduction in these dots by using plastic spatulas did not result in a significantly increased HPV positivity rate.

Nonisotopic human papillomavirus DNA typing of cervical smears obtained at the initial colposcopic examination.

To determine the prevalence of human papillomavirus (HPV) infection in 401 patients attending colposcopy for the first time, scraped cervical cells were investigated using dot blot hybridization and biotinylated DNA probes to HPV 6 and 11 (low-risk types) and 16, 18, and 33 (high-risk types). The HPV DNA was isolated from 52% of patients (low-risk types = 4%, high-risk types = 48%). Seventy-five percent had a cervical intraepithelial neoplasia (CIN)-condyloma. Low-risk types were infrequent (7%) and high-risk types (41%) predominant in condyloma/CIN I lesions when converse rates were expected. As CIN I lesions harboring high-risk types are at some risk of progressing to a higher grade dysplasia, colposcopic examination and treatment of this subgroup would seem justified. As expected, high-risk types were statistically associated with increasing grades of dysplasia. This hybridization method identified typeable HPV DNA in 60% of patients with a CIN-condyloma, and highlighted a unique HPV profile for this patient cohort.