S. Elizabeth McGregor

Physical Activity and Survival After Prostate Cancer

BACKGROUND Despite the high global prevalence of prostate cancer (PCa), few epidemiologic studies have assessed physical activity in relation to PCa survival. OBJECTIVE To evaluate different types, intensities, and timing of physical activity relative to PCa survival. DESIGN, SETTING, AND PARTICIPANTS A prospective study was conducted in Alberta, Canada, in a cohort of 830 stage II-IV incident PCa cases diagnosed between 1997 and 2000 with follow-up to 2014 (up to 17 yr). Prediagnosis lifetime activity was self-reported at diagnosis. Postdiagnosis activity was self-reported up to three times during follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Cox proportional hazards models related physical activity to all-cause and PCa-specific deaths and to first recurrence/progression of PCa. RESULTS AND LIMITATIONS A total of 458 deaths, 170 PCa-specific deaths, and, after first follow-up, 239 first recurrences/progressions occurred. Postdiagnosis total activity (>119 vs ≤42 metabolic equivalent [MET]-hours/week per year) was associated with a significantly lower all-cause mortality risk (hazard ratio [HR]: 0.58; 95% confidence interval [CI], 0.42-0.79; p value for trend <0.01). Postdiagnosis recreational activity (>26 vs ≤4 MET-hours/week per year) was associated with a significantly lower PCa-specific mortality risk (HR: 0.56; 95% CI, 0.35-0.90; p value for trend = 0.01). Sustained recreational activity before and after diagnosis (>18-20 vs <7-8 MET-hours/week per year) was associated with a lower risk of all-cause mortality (HR: 0.66; 95% CI, 0.49-0.88). Limitations included generalisability to healthier cases and an observational study design. CONCLUSIONS These findings support emerging recommendations to increase physical activity after the diagnosis of PCa and would inform a future exercise intervention trial examining PCa outcomes. PATIENT SUMMARY In a 17-yr prostate cancer (PCa) survival study, men who survived at least 2 yr who were more physically active postdiagnosis or performed more recreational physical activity before and after diagnosis survived longer. Recreational physical activity after diagnosis was associated with a lower risk of PCa death.

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.

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.

Measuring Preferences for Colorectal Cancer Screening: What are the Implications for Moving Forward?

There is a growing interest in the application of preferences to inform healthcare planning and delivery. Clinical practice guidelines are encouraging incorporation of preferences in patient management choices in recognition that often no single approach is best.The objective of this focused review is to provide an overview of the current state of preference measurement for colorectal cancer screening (CRCS) and highlight the implications for health policy, CRCS program implementation, and further research.MEDLINE and EMBASE electronic databases were searched (1990-May 2009) for English-language literature examining patient preferences for CRCS, using conjoint analysis methods. We systematically extracted information on the study population, whether the choice sets were framed around specific CRCS tests or the overall program, the attributes and levels included, and, where available, the ordering of importance of the attributes and key study findings.Qualitative data synthesis of key differences and commonalities in the approaches and findings are presented. Six conjoint analysis studies of CRCS were identified. While 66–88% of respondents in the general population indicated they would choose CRCS, this is greater than observed rates of uptake (40–50%). All studies were administered in a sample of the general population at average risk of CRC, except one that included a sample of physicians. The studies varied in the attributes and levels they included. However, accuracy, whether expressed in the context of a CRCS test or program, was consistently identified as a statistically significant and important attribute. Other attributes included in the conjoint analysis studies included level of discomfort during the test, preparation for the test, the testing process, frequency of testing, frequency of complications, the process of follow up, and cost.Our results suggested that (i) a majority of people would choose to be screened for CRC, although actual CRCS participation rates suggest otherwise; (ii) patients have distinct preferences for CRCS tests that can be linked to CRC test attributes; and consequently, (iii) there is no single CRCS test that is preferred by everyone. In addition, although the specific approach, attributes, and levels in the studies varied, they consistently found that multiple factors are important from the patient’s perspective and that preferences vary amongst subgroups. Consequently, careful consideration should be given to the design and implementation of a CRCS program based on a broader range of factors than the traditional outcomes such as mortality and incidence reduction. Attention should now be focused on how to use this information to inform health policy and develop CRCS programs that will increase screening uptake and adherence in the context of the health system in which the program will be provided. We propose a two-step process to designing and implementing a CRCS program based on evidence and preferences that informs patient choice.

Invasive squamous cell carcinoma of the cervix in women less than 35 years old: Recurrent versus nonrecurrent disease

Invasive cervical squamous cell carcinoma was diagnosed in 45 patients <35 years old from 1980 to 1985. Thirty-two cases were Stage IB; 10, Stage IIB; and three, Stage IIIB. Twenty-two patients developed persistent or recurrent disease. Only one of these is now alive with no evidence of tumor. The mean interval from diagnosis to recurrence was 8.7 months (median of 7.0) and from diagnosis to death was 14.7 months (median of 12.0). Eleven of 32 patients with Stage IB disease developed a recurrence; the intervals to recurrence in Stage IB disease were similar to those for more advanced stages. Factors predicting recurrence included advanced stage of the disease and tumor bulk (maximum size, depth of invasion, and number of involved quadrants) as well as an exophytic or ulcerative tumor and a symptomatic presentation. These factors may identify the patient at high risk for recurrence who would benefit from adjuvant therapy.

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.

Identification and prediction of health-related quality of life trajectories after a prostate cancer diagnosis

The aim of our study was to identify physical and mental health‐related quality of life (HRQoL) trajectories after a prostate cancer diagnosis and systematically characterize trajectories by behaviours and prognostic factors. Prostate cancer survivors (n = 817) diagnosed between 1997 and 2000 were recruited between 2000 and 2002 into a prospective repeated measurements study. Behavioural/prognostic data were collected through in‐person interviews and questionnaires. HRQoL was collected at three post‐diagnosis time‐points, approximately 2 years apart using the Short Form (SF)−36 validated questionnaire. To identify physical and mental HRQoL trajectories, group‐based trajectory modelling was undertaken. Differences between groups were evaluated by assessing influential dropouts (mortality/poor health), behavioural/prognostic factors at diagnosis or during the follow‐up. Three trajectories of physical HRQoL were identified including: average‐maintaining HRQoL (32.2%), low‐declining HRQoL (40.5%) and very low‐maintaining HRQoL (27.3%). In addition, three trajectories for mental HRQoL were identified: average‐increasing HRQoL (66.5%), above average‐declining HRQoL (19.7%) and low‐increasing HRQoL (13.8%). In both physical and mental HRQoL, dropout from mortality/poor health differed between trajectories, thus confirming HRQoL and mortality were related. Furthermore, increased Charlson comorbidity index score was consistently associated with physical and mental HRQoL group membership relative to average maintaining groups, while behaviours such as time‐varying physical activity was associated with physical HRQoL trajectories but not mental HRQoL trajectories. It was possible to define three trajectories of physical and mental HRQoL after prostate cancer. These data provide insights regarding means for identifying subgroups of prostate cancer survivors with lower or declining HRQoL after diagnosis whom could be targeted for interventions aimed at improving HRQoL.

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.

Post-diagnosis alcohol intake and prostate cancer survival: A population-based cohort study: Alcohol consumption and prostate cancer mortality

Alcohol consumption has been declared a Group 1 carcinogen by the International Agency for Research on Cancer (IARC) and is a potential risk factor for several types of cancer mortality. However, evidence for an association with prostate cancer survival remains inconsistent. We examined how alcohol consumption post‐diagnosis was associated with survival after prostate cancer diagnosis. Men diagnosed with prostate cancer (n = 829) in Alberta, Canada between the years 1997 and 2000 were recruited into a population‐based case–control study and then followed for up to 19 years for survival outcomes. Pre‐ and post‐diagnosis alcohol consumption, clinical characteristics and lifestyle factors were collected through in‐person interviews shortly after diagnosis and again 2–3 years post‐diagnosis. Cox proportional hazards were used to examine how post‐diagnosis alcohol consumption was associated with all‐cause and prostate cancer‐specific mortality (competing risk analysis too), in addition to first recurrence/progression or new primary cancer. Most participants reported drinking alcohol (≥once a month for 6 months) post‐diagnosis (n = 589, 71.0%). Exceeding Canadian Cancer Society (CCS) alcohol consumption recommendations (≥2 drinks/day) post‐diagnosis was associated with prostate cancer‐specific mortality relative to non‐drinkers (aHR: 1.82, 95% CI: 1.07–3.10) with borderline evidence of a linear trend. Interestingly, those in the highest quartile of drinks/week pre‐ and post‐diagnosis also had a twofold increase for prostate‐specific mortality (aHR: 2.67, 95% CI: 1.28–5.56) while controlling for competing risks. Our results support post‐diagnosis alcohol consumption was associated with increased mortality after prostate cancer diagnosis, specifically for prostate cancer‐related death. Future studies focused on confirming this burden of disease are warranted.

The association between recreational physical activity, sedentary time, and colorectal polyps in a population screened for colorectal cancer

PURPOSE Regular recreational moderate to vigorous physical activity (rMVPA) has been previously associated with a reduced risk of colorectal cancer (CRC), however, few studies have examined the association of rMVPA with colorectal polyps, the pre-malignant precursor lesions. The objective of this study was to examine the associations between physical activity and sitting time and polyps at the time of screening. METHODS We conducted a cross-sectional study of 2496 individuals undergoing screening-related colonoscopy in Calgary, Alberta, Canada. Physical activity and sitting time were characterized using hours of rMVPA, meeting physical activity recommendations and hours of sitting time using self-reported data obtained from the International Physical Activity Questionnaire. Logistic regression models were used to estimate the crude and adjusted odds ratios (OR) for presence of polyps associated with rMVPA and sitting time. RESULTS Meeting physical activity guidelines of ≥150 min/week was non-significantly associated with a modest decrease in odds of having ≥1 polyp at screening (ORadj = 0.95, 95% CI: 0.80-1.14). In males, threshold effects for sitting time were observed for up to 20 h/week (ORadj per hour sitting = 1.07, 95% CI: 1.01-1.13). In stratified analysis, larger inverse associations were observed between physical activity and the presence of polyps in females, obese individuals, and ever smokers, compared to pooled findings. CONCLUSIONS In this large CRC screening population, there was a suggestive association between increased rMVPA and reduced prevalence of polyps at screening, particularly among females. Even low amounts of regular sitting time (0-20 h/day) were associated with the presence of polyps, particularly among males. Further research on rMVPA and sitting time is necessary to better inform strategies to reduce the frequency of pre-malignant colorectal lesions.