Caitlyn A Senger

Liquid-Based Cytology and Human Papillomavirus Testing to Screen for Cervical Cancer: A Systematic Review for the U.S. Preventive Services Task Force

BACKGROUND Screening programs using conventional cytology have successfully reduced cervical cancer, but newer tests might enhance screening. PURPOSE To systematically review the evidence on liquid-based cytology (LBC) and high-risk human papillomavirus (HPV) screening for U.S. Preventive Services Task Force use in updating its 2003 recommendation. DATA SOURCES MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2000 through September 2010. STUDY SELECTION Two independent reviewers selected fair- to good-quality English-language studies that compared LBC or HPV-enhanced primary screening with conventional cytology in countries with developed population-based screening for cervical cancer. DATA EXTRACTION At least 2 independent reviewers critically appraised and rated the quality of studies and used standardized abstraction forms to extract data about test performance for detecting cervical intraepithelial neoplasia (CIN) and cancer and screening-related harms. DATA SYNTHESIS On the basis of 4 fair- to good-quality studies (141 566 participants), LBC had equivalent sensitivity and specificity to conventional cytology. Six fair- to good-quality diagnostic accuracy studies showed that 1-time HPV screening was more sensitive than cytology for detecting CIN3+/CIN2+ but was less specific. On the basis of 2 fair- to good-quality randomized, controlled trials (RCTs) (120 533 participants), primary HPV screening detected more cases of CIN3 or cancer in women older than 30 years. Four fair- to good-quality diagnostic accuracy studies and 4 fair- to good-quality RCTs showed mixed results of cotesting (HPV plus cytology) in women aged 30 years or older compared with cytology alone, with no clear advantage over primary HPV screening. Incomplete reporting of results for all screening rounds, including detection of disease and colposcopies, limits our ability to determine the net benefit of HPV-enhanced testing strategies. LIMITATION Resources were insufficient to gather unpublished data, short-term trial data showed possible ascertainment bias, and most RCTs used protocols that differed from current U.S. practice. CONCLUSION Evidence supports the use of LBC or conventional cytology for cervical cancer screening, but more complete evidence is needed before HPV-enhanced primary screening is widely adopted for women aged 30 years or older.

Ultrasonography Screening for Abdominal Aortic Aneurysms: A Systematic Evidence Review for the U.S. Preventive Services Task Force

An abdominal aortic aneurysm (AAA) is a weakening in the wall of the infrarenal aorta that results in an anteroposterior diameter of 3 cm or greater (1). Abdominal aortic aneurysms are often undiagnosed because a large proportion are asymptomatic until the development of rupture, which is generally acute and often fatal (59% to 83% of patients die before hospitalization) (2). Significant risk factors for the development of AAA include advanced age (3), male sex (4), smoking (1, 5, 6), and family history of AAAs (1, 7, 8). Other potential risk factors include a history of other vascular aneurysms (9), coronary artery disease (10), cerebrovascular disease (9), atherosclerosis (10), hypercholesterolemia (10), and hypertension (1, 10). Protective factors include black race, female sex, and diabetes mellitus (11). Smoking is the most important modifiable risk factor for AAA development (1214) and aneurysm growth (15). Older age, female sex, smoking, and higher blood pressure are associated with increased risk for rupture in patients with small (3.0 to 5.4 cm) AAAs (15). Although several screening methods exist, ultrasonography is accepted as the standard screening imaging method for AAA because it has a high sensitivity (94% to 100%) and specificity (98% to 100%) (1, 2, 1619). Ultrasonography is noninvasive, can be conducted at a low cost, and does not involve radiation exposure. Computed tomography scans are highly sensitive and specific in detecting AAAs but are not recommended for first-line screening because of high cost and radiation exposure (1, 20). In 2005, the U.S. Preventive Services Task Force (USPSTF) found good evidence to recommend 1-time screening for AAA by ultrasonography in men aged 65 to 75 years who have ever smoked (B recommendation). The USPSTF concluded that the benefits of screening did not clearly outweigh the harms and did not make a general recommendation for or against screening for AAA in men aged 65 to 75 years who have never smoked (C recommendation). The USPSTF recommended against routine screening for AAA in women (D recommendation) (21). This systematic review includes newly identified literature and all trials from the previous review that meet current inclusion criteria to provide updated evidence on the effectiveness of 1-time and repeated ultrasonography screening for AAAs (6). Supplement. Original Version (PDF) Methods Detailed methods are publicly available in our full evidence report and its appendices (www.uspreventiveservicestaskforce.org) (22). This review addressed the following key questions: the effect of 1-time screening for AAAs of all sizes (3.0 cm) and repeated screening for initially normal-sized aortas (<3.0 cm) on health outcomes and the harms related to 1-time and repeated screening for AAAs (Appendix Figure). Of note, our detailed critique of treatment evidence for AAAs identified through screening that did not meet the currently accepted treatment threshold of 5 cm is presented in the full evidence report. Appendix Figure. Analytic framework and key questions. AAA = abdominal aortic aneurysm; COPD = chronic obstructive pulmonary disease; EVAR = endovascular aneurysm repair; QOL = quality of life. Data Sources and Searches We searched MEDLINE, the Database of Abstracts of Reviews of Effects, and the Cochrane Central Register of Controlled Trials for relevant English-language studies published between January 2004 and January 2013. We searched for screening trials through September 2013 in MEDLINE. We supplemented searches with suggestions from experts and considered all articles included in the previous review for the USPSTF. We also reviewed reference lists of relevant systematic reviews and meta-analyses. Study Selection Two investigators independently reviewed abstracts and full-text articles for inclusion according to predetermined criteria. We resolved discrepancies through consensus with a third investigator. We considered randomized, controlled trials (RCTs) and large cohort studies (1000 participants) of asymptomatic adult populations for key questions examining the effectiveness of 1-time and repeated screening. For the key question examining the harms of screening for AAAs, we considered RCTs and observational studies. Ultrasonography was the only screening method we considered. For all bodies of evidence, we excluded studies that we rated as poor-quality on the basis of the USPSTF quality rating standards (23). Data Extraction and Quality Assessment One investigator extracted data, and a second investigator reviewed these data. Two investigators completed independent critical appraisals of all relevant studies by using the USPSTFs design-specific criteria (23), the National Institute for Health and Care Excellence method checklists (24), the Quality Assessment of Diagnostic Accuracy Studies (25) tool, and the Newcastle-Ottawa Scale (26). According to the USPSTF criteria, a good-quality study met all prespecified standards. A fair-quality study did not meet (or it was unclear whether it met) at least 1 criterion, but it also had no known limitation that could invalidate its results. A poor-quality study had a single fatal flaw or several important limitations that would likely bias results. Data Synthesis and Analysis We qualitatively synthesized data for each key question by summarizing relevant details and results for each included study. Although we decided a priori to pool studies for all outcomes using DerSimonianLaird random-effects models, we report quantitative analyses only for all-cause mortality. When we pooled AAA-related mortality and screening harms, the summary effects showed high statistical heterogeneity at the longest follow-up. Thus, we present forest plots with no pooled summaries. In addition, we did not pool studies examining the effectiveness of rescreening because of substantial differences in patient population, length of follow-up, and reported outcomes. For all pooled results using the DerSimonianLaird random-effects models, see the full evidence report (22). For all-cause mortality, we conducted planned random-effects analyses using the DerSimonianLaird method (27). We conducted sensitivity analyses using a fixed-effects model as well as the profile likelihood method because there were only 3 trials and the DerSimonianLaird method can underestimate uncertainty when the number of trials is small (27, 28). The 2 methods resulted in identical effect estimates and CIs. We examined heterogeneity across trials with the I 2 statistic and chi-square test for heterogeneity. Role of the Funding Source This study was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. Members of the USPSTF and the AHRQ medical officer assisted in the development of the reviews scope. Approval from AHRQ was required before the manuscript could be submitted for publication, but the authors are solely responsible for its content and the decision to submit it for publication. Results We reviewed 2723 abstracts and 204 full-text articles and identified 4 trials addressing the benefits of 1-time screening, 10 studies on the effectiveness of rescreening, 7 studies addressing the harms of 1-time and repeated screening, 15 trials examining the benefits of treating small AAAs, and 15 studies on the harms associated with treating small AAAs (Figure 1). The evidence related to the treatment of small AAAs is discussed in our full evidence report (22), along with detailed study-level and summary results of the evidence related to AAA screening. Figure 1. Summary of evidence search and selection. AAA = abdominal aortic aneurysm; KQ = key question. * Evidence related to the treatment of small AAAs is included in the full evidence report (22). One study was excluded for study design and outcomes. AAA Screening in Men We identified 2 fair-quality and 2 good-quality population-based screening RCTs (137214 participants) that assessed the efficacy of AAA screening in population-based settings: MASS (Multicentre Aneurysm Screening Study) (2932); the Chichester, United Kingdom screening trial (3336); the Viborg County, Denmark screening trial (3741); and the western Australian screening trial (42) (Table 1). All trials used population registries or regional health directories to identify potential participants aged 64 or 65 years or older. The Chichester trial (33) was the only trial that included women (34). No trial reported outcomes by demographic characteristics other than age and sex. Three of the 4 trials described adequate randomization (30, 33, 37). Three had no trial exclusions, whereas MASS excluded patients who were identified as being too high-risk to be screened by their primary care physicians, were terminally ill, or had other serious health problems or previous AAA repair (30). All trials randomly assigned participants to usual care or invitation for 1-time ultrasonography screening. Three specified postscreening ultrasonography surveillance protocols for AAAs measuring 3.0 cm or greater (30, 33, 39), whereas the western Australian trial sent initial ultrasound results to primary care physicians for further management (42). Table 1. Methodological and Intervention Characteristics of the 4 Included Population-Based AAA Screening Randomized, Controlled Trials All trials used intention-to-treat analysis. Adherence to screening varied from the lowest in the western Australian trial (62.5% of invited attended screening) to the greatest in MASS (80.2% adherence). Less than 1% of the control group crossed over in any trial to receive elective surgery, even at the longest follow-up of 13 to 15 years. The primary trial outcome was AAA-specific mortality (defined as all AAA deaths plus all deaths within 30 days of AAA surgical repair). Trials also reported AAA rupture and all-cause mortality rates. Deaths and their causes were ascertained from death certificates in all studies, and 3 used a blinded ad

Risk Factors and Other Epidemiologic Considerations for Cervical Cancer Screening: A Narrative Review for the U.S. Preventive Services Task Force

Despite the success of cervical cancer screening programs, questions remain about the appropriate time to begin and end screening. This review explores epidemiologic and contextual data on cervical cancer screening to inform decisions about when screening should begin and end. Cervical cancer is rare among women younger than 20 years. Screening for cervical cancer in this age group is complicated by lower rates of detection and higher rates of false-positive results than in older women. Methods used to diagnose and treat cervical intraepithelial neoplasia have important potential adverse effects. High-risk human papillomavirus infections and abnormalities on cytologic and histologic examination have relatively high rates of regression. Accordingly, cervical cancer screening in women younger than 20 years may be harmful. The incidence of, and mortality rates from, cervical cancer and the proportion of U.S. women aged 65 years or older who have had a Papanicolaou smear within 3 years have decreased since 2000. Available evidence supports discontinuation of cervical cancer screening among women aged 65 years or older who have had adequate screening and are not otherwise at high risk. Further reductions in the burden of cervical cancer in older women are probably best achieved by focusing on screening those who have not been adequately screened.