Louise Wideroff

Hereditary breast/ovarian and colorectal cancer genetics knowledge in a national sample of US physicians

Background: Clinically relevant genetics knowledge is essential for appropriate assessment and management of inherited cancer risk, and for effective communication with patients. This national physician survey assessed knowledge regarding basic cancer genetics concepts early in the process of introduction of predictive genetic testing for breast/ovarian and hereditary non-polyposis colorectal cancer (HNPCC) syndromes. Methods: A stratified random sample was selected from the American Medical Association Masterfile of all licensed physicians. In total, 1251 physicians (820 in primary care, 431 in selected subspecialties) responded to a 15 minute questionnaire (response rate 71%) in 1999–2000. Multivariate logistic regression analyses were conducted to identify demographic and practice characteristics associated with accurate response to three knowledge questions. Results: Of the study population, 37.5% was aware of paternal inheritance of BRCA1/2 mutations, and 33.8% recognised that these mutations occur in <10% of breast cancer patients. Only 13.1% accurately identified HNPCC gene penetrance as ⩾50%. Obstetrics/gynaecology physicians, oncologists, and general surgeons were significantly more likely than general and family practitioners to respond accurately to the breast/ovarian questions, as were gastroenterologists to the HNPCC question. Conclusions: These nationally representative data indicate limited physician knowledge about key cancer genetics concepts in 1999–2000, particularly among general primary care physicians. Specialists were more knowledgeable about syndromes they might treat or refer elsewhere. Recent dissemination of practice guidelines and continued expansion of relevant clinical literature may enhance knowledge over time. In addition to educational efforts to assist physicians with the growing knowledge base, more research is needed to characterise the organisational changes required within the healthcare system to provide effective cancer genetics services.

Cervical Cancer Screening With Both Human Papillomavirus and Papanicolaou Testing vs Papanicolaou Testing Alone: What Screening Intervals Are Physicians Recommending?

BACKGROUND Guidelines recommend screening for cervical cancer among women 30 years or older 3 years after a normal Papanicolaou test (hereinafter referred to as Pap test) result or a combined normal screening result (normal Pap/negative human papillomavirus [HPV] test results). We assessed reported recommendations by US primary care physicians (PCPs) on screening intervals that incorporate HPV cotesting compared with Pap testing alone. METHODS From September 1, 2006, through May 31, 2007, we conducted a mailed survey of a representative sample of 1212 PCPs, of whom 950 performed Pap tests and recommended the HPV test for screening or management. The main outcome measure included self-reported data on timing of screening intervals for women with normal results using clinical vignettes. RESULTS Among Pap test providers who recommend HPV testing, 31.8% reported that they would conduct the next Pap test in 3 years for a 35-year-old woman with 3 normal Pap test results. For a 35-year-old woman with a normal Pap test result and a negative HPV test finding, only 19.0% would conduct the next Pap test in 3 years. Most remaining physicians would conduct the Pap test more frequently. Most PCPs did not recommend a second HPV test or recommended the next HPV test at the same frequency as the Pap test. Physician specialty was strongly associated with guideline-consistent recommendations for the next Pap or HPV test. CONCLUSIONS A lower proportion of PCPs recommend extending screening intervals to 3 years with an HPV cotest than those screening with the Pap test alone. Implementation of effective interventions and strategies that improve physician adherence to recommendations will be important for efficient screening practices.

Awareness of genetic testing for increased cancer risk in the year 2000 National Health Interview Survey.

Objectives: This study explores factors associated with differential awareness of genetic tests for increased cancer risk in the US. Methods: 27,405 respondents from the 2000 National Health Interview Survey, ages 25+, were asked if they had heard of these tests. Results: 44.4% said ‘yes’, including 49.9% of whites, 32.9% of African-Americans, 32.3% of American Indians/Alaskan Natives, 28.0% of Asian/Pacific Islanders, and 20.6% of Hispanics. In multivariate analysis, test awareness was significantly associated with higher education, white race, age <60 years, female gender, private health insurance, personal or parent’s history of certain cancers, physical activity, and vitamin/supplement use, among other factors. Conclusions: The survey showed which population subgroups may lack access to cancer genetics information and may therefore benefit from targeted strategies to ensure risk-appropriate utilization of genetic counseling and testing.

Confirmation of Family Cancer History Reported in a Population-Based Survey

BACKGROUND Knowledge of family cancer history is essential for estimating an individuals cancer risk and making clinical recommendations regarding screening and referral to a specialty cancer genetics clinic. However, it is not clear if reported family cancer history is sufficiently accurate for this purpose. METHODS In the population-based 2001 Connecticut Family Health Study, 1019 participants reported on 20 578 first-degree relatives (FDR) and second-degree relatives (SDR). Of those, 2605 relatives were sampled for confirmation of cancer reports on breast, colorectal, prostate, and lung cancer. Confirmation sources included state cancer registries, Medicare databases, the National Death Index, death certificates, and health-care facility records. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for reports on lung, colorectal, breast, and prostate cancer and after stratification by sex, age, education, and degree of relatedness and used to estimate report accuracy. Pairwise t tests were used to evaluate differences between the two strata in each stratified analysis. All statistical tests were two-sided. RESULTS Overall, sensitivity and positive predictive value were low to moderate and varied by cancer type: 60.2% and 40.0%, respectively, for lung cancer reports, 27.3% and 53.5% for colorectal cancer reports, 61.1% and 61.3% for breast cancer reports, and 32.0% and 53.4% for prostate cancer reports. Specificity and negative predictive value were more than 95% for all four cancer types. Cancer history reports on FDR were more accurate than reports on SDR, with reports on FDR having statistically significantly higher sensitivity for prostate cancer than reports on SDR (58.9% vs 21.5%, P = .002) and higher positive predictive value for lung (78.1% vs 31.7%, P < .001), colorectal (85.8% vs 43.5%, P = .004), and breast cancer (79.9% vs 53.6%, P = .02). CONCLUSIONS General population reports on family history for the four major adult cancers were not highly accurate. Efforts to improve accuracy are needed in primary care and other health-care settings in which family history is collected to ensure appropriate risk assessment and clinical care recommendations.

U.S. geographic distribution of prevaccine era cervical cancer screening, incidence, stage, and mortality.

Background: Cervical cancer prevention programs are being reconfigured to incorporate human papillomavirus (HPV) testing and vaccination. To define priority areas for prevention efforts, we examined the geographic distribution of cervical cancer screening, incidence, stage, and mortality in the United States, prior to the introduction of HPV-based prevention technologies. Methods: County-level cervical cancer incidence data from 37 central registries were obtained from Surveillance, Epidemiology, and End Results and North American Association of Central Cancer Registries. A spatial–temporal model that accounted for demographic and behavioral attributes was used to generate a complete view of county-level incidence from 1995 to 2004, including counties with missing data. Distribution of stage at diagnosis was examined by registry. Counties with high mortality and infrequent screening were identified using vital statistics and newly available county-level screening estimates. Results: Compared with non-Hispanic whites and Asian and Pacific Islanders, incidence rates were higher among non-Hispanic black, American Indian and Alaska Native, and Hispanic women. Counties with infrequent screening often experienced elevated incidence and mortality rates and were located in states with suboptimal stage at diagnosis profiles. Affected areas included Appalachia, the southeastern Atlantic states, and the lower Mississippi Valley. Elevated death rates were experienced in central counties of large metropolitan areas. Conclusions: Geographic and racial/ethnic variability were evident in cervical cancer incidence and mortality. Women living in areas with endemic poverty would benefit from access to HPV-based prevention technologies. Impact: These findings provide a baseline for monitoring progress in cervical cancer control in the era of HPV-based prevention. Cancer Epidemiol Biomarkers Prev; 20(4); 591–9. ©2011 AACR.

Risk of cancer after blood transfusion from donors with subclinical cancer: a retrospective cohort study

BACKGROUND Although mechanisms for detection of short-term complications after blood transfusions are well developed, complications with delayed onset, notably transmission of chronic diseases such as cancer, have been difficult to assess. Our aim was to investigate the possible risk of cancer transmission from blood donors to recipients through blood transfusion. METHODS We did a register-based retrospective cohort study of cancer incidence among patients who received blood from donors deemed to have a subclinical cancer at the time of donation. These precancerous donors were diagnosed with a cancer within 5 years of the donation. Data from all computerised blood bank registers in Sweden and Denmark gathered between 1968 and 2002 were merged into a common database. Demographic and medical data, including mortality and cancer incidence, were ascertained through linkages with nationwide, and essentially complete, population and health-care registers. The risk of cancer in exposed recipients relative to that in recipients who received blood from non-cancerous donors was estimated with multivariate Poisson regression, adjusting for potential confounding factors. FINDINGS Of the 354 094 transfusion recipients eligible for this analysis, 12,012 (3%) were exposed to blood products from precancerous donors. There was no excess risk of cancer overall (adjusted relative risk 1.00, 95% CI 0.94-1.07) or in crude anatomical subsites among recipients of blood from precancerous donors compared with recipients of blood from non-cancerous donors. INTERPRETATION Our data provide no evidence that blood transfusions from precancerous blood donors are associated with increased risk of cancer among recipients compared with transfusions from non-cancerous donors.

A population-based binational register for monitoring long-term outcome and possible disease concordance among blood donors and recipients

Background and Objectives  Even with appropriate donor deferrals and advanced screening tests, the risk of disease transmission through blood transfusion cannot be completely disregarded. Efficient monitoring of possible disease transmission between blood donors and recipients should be an important component of a comprehensive haemovigilance system.

Human papillomavirus and cervical cancer behavioral surveillance in the US

In the US, federal and state behavioral surveillance systems routinely monitor self‐reported sexual behavior and Papanicolaou (Pap) test use to identify high‐risk populations, trends, and disparities and to guide and evaluate interventions for cervical cancer prevention and control. Clinical uptake of human papillomavirus (HPV) vaccination and testing necessitates the expansion of behavioral surveillance systems. Cervical disease is the main focus of HPV‐related behavioral surveillance because of greater cancer incidence and mortality relative to other susceptible organs, and the availability of effective technologies for prevention and control. In the current study, a framework is presented for the types of behaviors to monitor, their conceptual and operational definitions, target populations, and evidence supporting the reliability and validity of self‐report measures. An overview is also provided of 8 population‐based and 2 provider‐based data systems that are nationally representative and accessible for behavioral surveillance research. Ongoing surveillance at the national, state, and local level is critical for monitoring the dissemination of HPV technologies and their impact on reducing disparities in the detection of precursor lesions, incidence of invasive cancer, and mortality. Cancer 2008;113:(10 suppl):3013–30. Published 2008 by the American Cancer Society.

A case-control study of human papillomavirus and cervical squamous intraepithelial lesions (SIL) in Harris County, Texas: differences among racial/ethnic groups

We conducted a case-control study of the association between SIL and HPV among whites (W), African Americans (AA), and Hispanics (H) in Harris County, Texas. Cases were identified at M.D. Anderson Cancer Center Colposcopy Clinic. Controls were identified among women obtaining routine Pap screening at two Harris County Health Department Clinics. HPV was detected by a PCR-based fluorescent assay. Dichotomous and polytomous logistic regression models were used to estimate adjusted odd ratios (AOR) and 95% confidence intervals (CI) for SIL among racial/ethnic groups and grade of disease. Prevalence of HPV infection was 64% in low grade SIL (LSIL), 84% in high grade SIL (HSIL), and 19% in controls. Risk of SIL was higher in H than in W and AA, AOR 29.5 (12.4-70.5), 15.3 (6.0-33.8), and 5.8 (2.6-12.6), respectively. Similarly, racial/ethnic differences were observed for both LSIL (AOR = 16.6, 7.7, and 4.3, respectively) and HSIL (AOR = 78.6, 34.6, and 14.2, respectively). Findings support the association between SIL and HPV and differences in the strength of the association with LSILs and HSILs. Data also suggest a higher risk for H and a lower risk for AA.

A Health Services Research Agenda for Cellular, Molecular and Genomic Technologies in Cancer Care

Background: In recent decades, extensive resources have been invested to develop cellular, molecular and genomic technologies with clinical applications that span the continuum of cancer care. Methods: In December 2006, the National Cancer Institute sponsored the first workshop to uniquely examine the state of health services research on cancer-related cellular, molecular and genomic technologies and identify challenges and priorities for expanding the evidence base on their effectiveness in routine care. Results: This article summarizes the workshop outcomes, which included development of a comprehensive research agenda that incorporates health and safety endpoints, utilization patterns, patient and provider preferences, quality of care and access, disparities, economics and decision modeling, trends in cancer outcomes, and health-related quality of life among target populations. Conclusions: Ultimately, the successful adoption of useful technologies will depend on understanding and influencing the patient, provider, health care system and societal factors that contribute to their uptake and effectiveness in ‘real-world’ settings.