Special Issue "Ovarian Cancer Screening"

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (30 June 2017)

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Guest Editor
Dr. Edward J. Pavlik

Director of Ovarian Screening Research in Gynecologic Oncology, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA
Website | E-Mail
Interests: ovarian cancer; cancer screening; tumor imaging

Special Issue Information

Dear Colleagues,

Ovarian cancer is deadly, claiming more women than all other gynecological malignancies combined. However, when detected at an early stage ovarian cancer is highly curable. Consequently, screening efforts are likely to be the best way to detect early stage disease. The forthcoming Special Issue focuses on several key elements that are essential for an understanding of ovarian cancer screening:

  1. Screening trial design, make-up and execution. Considerations must choose a design that is protocol driven vs. a random control trial, age of participants, periods for screening and follow-up and events to be censored.
  2. Treatment of women identified by screening. Time to treatment must be minimized so that an early stage detect is not permitted to progress to an advanced stage. Importantly, treatment must be optimized for the best possible outcomes by utilizing gynecologic oncologists.
  3. Collateral affectors in screening. Both perceptions of well being and potential complications of treatment should be considered as confounders of compliance.
  4. Endpoints and efficacy. Early stage detection, disease specific survival, overall survival and avoidance of an ovarian cancer death can each be considered as an endpoint, Considerations of screen performance and cost determine efficacy.
  5. Interpretation of ovarian screening trials. Comparisons between screening trials conducted in the United States, the United Kingdom and Japan are informative regarding the current status of ovarian screening.

Prof. Dr. Edward J. Pavlik
Guest Editor

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Keywords

  • ovarian cancer
  • screening
  • trail design
  • treatment
  • collateral affectors
  • endpoints
  • costs
  • efficacy

Related Special Issue

Published Papers (11 papers)

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Editorial

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Open AccessEditorial
Ovarian Cancer Screening: Lessons about Effectiveness
Received: 18 December 2017 / Revised: 27 December 2017 / Accepted: 29 December 2017 / Published: 29 December 2017
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Abstract
Ovarian cancer screening has been described in scientific reports [1–4], as well as in reviews and summaries[...] Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available

Research

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Open AccessArticle
Validation of the Performance of International Ovarian Tumor Analysis (IOTA) Methods in the Diagnosis of Early Stage Ovarian Cancer in a Non-Screening Population
Diagnostics 2017, 7(2), 32; https://doi.org/10.3390/diagnostics7020032
Received: 28 March 2017 / Revised: 25 May 2017 / Accepted: 26 May 2017 / Published: 2 June 2017
Cited by 1 | PDF Full-text (226 KB) | HTML Full-text | XML Full-text
Abstract
Background: The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy. Methods: This is a secondary analysis of a prospective multicenter [...] Read more.
Background: The aim of this study was to assess and compare the performance of different ultrasound-based International Ovarian Tumor Analysis (IOTA) strategies and subjective assessment for the diagnosis of early stage ovarian malignancy. Methods: This is a secondary analysis of a prospective multicenter cross-sectional diagnostic accuracy study that included 1653 patients recruited at 18 centers from 2009 to 2012. All patients underwent standardized transvaginal ultrasonography by experienced ultrasound investigators. We assessed test performance of the IOTA Simple Rules (SRs), Simple Rules Risk (SRR), the Assessment of Different NEoplasias in the adneXa (ADNEX) model and subjective assessment to discriminate between stage I-II ovarian cancer and benign disease. Reference standard was histology after surgery. Results: 230 (13.9%) patients proved to have stage I–II primary invasive ovarian malignancy, and 1423 (86.1%) had benign disease. Sensitivity and specificity with respect to malignancy (95% confidence intervals) of the original SRs (classifying all inconclusive cases as malignant) were 94.3% (90.6% to 96.7%) and 73.4% (71.0% to 75.6%). Subjective assessment had a sensitivity and specificity of 90.0% (85.4% to 93.2%) and 86.7% (84.9% to 88.4%), respectively. The areas under the receiver operator characteristic curves of SRR and ADNEX were 0.917 (0.902 to 0.933) and 0.905 (0.920 to 0.934), respectively. At a 1% risk cut-off, sensitivity and specificity for SRR were 100% (98.4% to 100%) and 38.0% (35.5% to 40.6%), and for ADNEX were 100% (98.4% to 100%) and 19.4% (17.4% to 21.5%). At a 30% risk cut-off, sensitivity and specificity for SRR were 88.3% (83.5% to 91.8%) and 81.1% (79% to 83%), and for ADNEX were 84.5% (80.5% to 89.6%) and 84.5% (82.6% to 86.3%). Conclusion: This study shows that all three IOTA strategies have good ability to discriminate between stage I-II ovarian malignancy and benign disease. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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Open AccessArticle
Ovarian Cancer Incidence Corrected for Oophorectomy
Diagnostics 2017, 7(2), 19; https://doi.org/10.3390/diagnostics7020019
Received: 30 December 2016 / Revised: 1 March 2017 / Accepted: 18 March 2017 / Published: 1 April 2017
Cited by 2 | PDF Full-text (379 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Current reported incidence rates for ovarian cancer may significantly underestimate the true rate because of the inclusion of women in the calculations who are not at risk for ovarian cancer due to prior benign salpingo-oophorectomy (SO). We have considered prior SO to more [...] Read more.
Current reported incidence rates for ovarian cancer may significantly underestimate the true rate because of the inclusion of women in the calculations who are not at risk for ovarian cancer due to prior benign salpingo-oophorectomy (SO). We have considered prior SO to more realistically estimate risk for ovarian cancer. Kentucky Health Claims Data, International Classification of Disease 9 (ICD-9) codes, Current Procedure Terminology (CPT) codes, and Kentucky Behavioral Risk Factor Surveillance System (BRFSS) Data were used to identify women who have undergone SO in Kentucky, and these women were removed from the at-risk pool in order to re-assess incidence rates to more accurately represent ovarian cancer risk. The protective effect of SO on the population was determined on an annual basis for ages 5–80+ using data from the years 2009–2013. The corrected age-adjusted rates of ovarian cancer that considered SO ranged from 33% to 67% higher than age-adjusted rates from the standard population. Correction of incidence rates for ovarian cancer by accounting for women with prior SO gives a better understanding of risk for this disease faced by women. The rates of ovarian cancer were substantially higher when SO was taken into consideration than estimates from the standard population. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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Open AccessArticle
Symptoms Relevant to Surveillance for Ovarian Cancer
Diagnostics 2017, 7(1), 18; https://doi.org/10.3390/diagnostics7010018
Received: 13 December 2016 / Revised: 1 March 2017 / Accepted: 13 March 2017 / Published: 20 March 2017
Cited by 2 | PDF Full-text (409 KB) | HTML Full-text | XML Full-text
Abstract
To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi [...] Read more.
To examine how frequently and confidently healthy women report symptoms during surveillance for ovarian cancer. A symptoms questionnaire was administered to 24,526 women over multiple visits accounting for 70,734 reports. A query of reported confidence was included as a confidence score (CS). Chi square, McNemars test, ANOVA and multivariate analyses were performed. 17,623 women completed the symptoms questionnaire more than one time and >9500 women completed it more than one four times for >43,000 serially completed questionnaires. Reporting ovarian cancer symptoms was ~245 higher than ovarian cancer incidence. The positive predictive value (0.073%) for identifying ovarian cancer based on symptoms alone would predict one malignancy for 1368 cases taken to surgery due to reported symptoms. Confidence on the first questionnaire (83.3%) decreased to 74% when more than five questionnaires were completed. Age-related decreases in confidence were significant (p < 0.0001). Women reporting at least one symptom expressed more confidence (41,984/52,379 = 80.2%) than women reporting no symptoms (11,882/18,355 = 64.7%), p < 0.0001. Confidence was unrelated to history of hormone replacement therapy or abnormal ultrasound findings (p = 0.30 and 0.89). The frequency of symptoms relevant to ovarian cancer was much higher than the occurrence of ovarian cancer. Approximately 80.1% of women expressed confidence in what they reported. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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Open AccessArticle
Complications from Surgeries Related to Ovarian Cancer Screening
Diagnostics 2017, 7(1), 16; https://doi.org/10.3390/diagnostics7010016
Received: 7 December 2016 / Revised: 24 February 2017 / Accepted: 28 February 2017 / Published: 8 March 2017
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Abstract
The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients [...] Read more.
The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988–2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients. Another 142 patients with incomplete records were interviewed by phone. Complete information was available for 548 patients. Complications were graded using the Clavien–Dindo (C–D) Classification of Surgical Complications and considered minor if assigned Grade I (any deviation from normal course, minor medications) or Grade II (other pharmacological treatment, blood transfusion). C–D Grade III complications (those requiring surgical, endoscopic, or radiologic intervention) and C–D Grade IV complications (those which are life threatening) were considered “major”. Statistical analysis was performed using SAS 9.4 software. Complications were documented in 54/548 (10%) subjects. For women with malignancy, 17/90 (19%) had complications compared to 37/458 (8%) with benign pathology (p < 0.003). For non-cancer surgery, obesity was associated with increased complications (p = 0.0028). Fifty patients had minor complications classified as C–D Grade II or less. Three of 4 patients with Grade IV complications had malignancy (p < 0.0004). In the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial, 212 women had surgery for ovarian malignancy, and 95 had at least one complication (45%). Of the 1080 women with non-cancer surgery, 163 had at least one complication (15%). Compared to the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial, the Kentucky Ovarian Cancer Screening Program had significantly fewer complications from both cancer and non-cancer surgery (p < 0.0001 and p = 0.002, respectively). Complications resulting from surgery performed as a result of the Kentucky Ovarian Cancer Screening Program were infrequent and significantly fewer than reported in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Complications were mostly minor (93%) and were more common in cancer versus non-cancer surgery. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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Review

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Open AccessReview
Ultrasound Monitoring of Extant Adnexal Masses in the Era of Type 1 and Type 2 Ovarian Cancers: Lessons Learned From Ovarian Cancer Screening Trials
Diagnostics 2017, 7(2), 25; https://doi.org/10.3390/diagnostics7020025
Received: 9 January 2017 / Revised: 11 April 2017 / Accepted: 24 April 2017 / Published: 28 April 2017
Cited by 1 | PDF Full-text (22906 KB) | HTML Full-text | XML Full-text
Abstract
Women that are positive for an ovarian abnormality in a clinical setting can have either a malignancy or a benign tumor with probability favoring the benign alternative. Accelerating the abnormality to surgery will result in a high number of unnecessary procedures that will [...] Read more.
Women that are positive for an ovarian abnormality in a clinical setting can have either a malignancy or a benign tumor with probability favoring the benign alternative. Accelerating the abnormality to surgery will result in a high number of unnecessary procedures that will place cost burdens on the individual and the health delivery system. Surveillance using serial ultrasonography is a reasonable alternative that can be used to discover if changes in the ovarian abnormality will occur that favor either a malignant or benign interpretation. Several ovarian cancer screening trials have had extensive experiences with changes in subclinical ovarian abnormalities in normal women that can define growth, stability or resolution and give some idea of the time frame over which changes occur. The present report examines these experiences and relates them to the current understanding of ovarian cancer ontology, presenting arguments related to the benefits of surveillance. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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Open AccessReview
Ten Important Considerations for Ovarian Cancer Screening
Diagnostics 2017, 7(2), 22; https://doi.org/10.3390/diagnostics7020022
Received: 4 January 2017 / Revised: 5 April 2017 / Accepted: 7 April 2017 / Published: 13 April 2017
Cited by 3 | PDF Full-text (803 KB) | HTML Full-text | XML Full-text
Abstract
The unique intricacies of ovarian cancer screening and perspectives of different screening methods are presented as ten considerations that are examined. Included in these considerations are: (1) Deciding on the number of individuals to be screened; (2) Anticipating screening group reductions due to [...] Read more.
The unique intricacies of ovarian cancer screening and perspectives of different screening methods are presented as ten considerations that are examined. Included in these considerations are: (1) Deciding on the number of individuals to be screened; (2) Anticipating screening group reductions due to death; (3) Deciding on the duration and frequency of screening; (4) Deciding on an appropriate follow-up period after screening; (5) Deciding on time to surgery when malignancy is suspected; (6) Deciding on how screen-detected ovarian cancers are treated and by whom; (7) Deciding on how to treat the data of enrolled participants; (8) Deciding on the most appropriate way to assign disease-specific death; (9) Deciding how to avoid biases caused by enrollments that attract participants with late-stage disease who are either symptomatic or disposed by factors that are genetic, environmental or social; and (10) Deciding whether the screening tool or a screening process is being tested. These considerations are presented in depth along with illustrations of how they impact the outcomes of ovarian cancer screening. The considerations presented provide alternative explanations of effects that have an important bearing on interpreting ovarian screening outcomes. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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Open AccessReview
Psychological and Behavioral Impact of Participation in Ovarian Cancer Screening
Diagnostics 2017, 7(1), 15; https://doi.org/10.3390/diagnostics7010015
Received: 30 December 2016 / Revised: 22 February 2017 / Accepted: 6 March 2017 / Published: 8 March 2017
Cited by 2 | PDF Full-text (209 KB) | HTML Full-text | XML Full-text
Abstract
Evaluation of costs and benefits associated with cancer screening should include consideration of any psychological and behavioral impact associated with screening participation. Research examining the psychological and behavioral impact of screening asymptomatic women for ovarian cancer (OC) was considered. Research has focused upon [...] Read more.
Evaluation of costs and benefits associated with cancer screening should include consideration of any psychological and behavioral impact associated with screening participation. Research examining the psychological and behavioral impact of screening asymptomatic women for ovarian cancer (OC) was considered. Research has focused upon potential negative psychological (e.g., distress) and behavioral (e.g., reduced future screening participation) impact of false positive (FP) OC test results. Results suggest FP OC screening results are associated with greater short-term OC-specific distress. While distress dissipates over time it may remain elevated relative to pre-screening levels for several weeks or months even after clinical follow-up has ruled out malignancy. The likelihood of participation in future OC screening may also be reduced. Research focused upon identification of any beneficial impact of participation in OC screening associated with receipt of “normal” results was also considered. This research suggests that a “normal” screening test result can have psychological benefits, including increased positive affect and beliefs in the efficacy of screening. It is concluded that any psychological or behavioral harms attributable to OC screening are generally very modest in severity and duration and might be counterbalanced by psychological benefits accruing to women who participate in routine OC screening and receive normal test results. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
Open AccessReview
Subtypes of Ovarian Cancer and Ovarian Cancer Screening
Diagnostics 2017, 7(1), 12; https://doi.org/10.3390/diagnostics7010012
Received: 27 December 2016 / Revised: 23 February 2017 / Accepted: 27 February 2017 / Published: 2 March 2017
Cited by 10 | PDF Full-text (207 KB) | HTML Full-text | XML Full-text
Abstract
Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics [...] Read more.
Ovarian cancer is the foremost cause of gynecological cancer death in the developed world, as it is usually diagnosed at an advanced stage. In this paper we discuss current issues, the efficacy and problems associated with ovarian cancer screening, and compare the characteristics of ovarian cancer subtypes. There are two types of ovarian cancer: Type I carcinomas, which are slow-growing, indolent neoplasms thought to arise from a precursor lesion, which are relatively common in Asia; and Type II carcinomas, which are clinically aggressive neoplasms that can develop de novo from serous tubal intraepithelial carcinomas (STIC) and/or ovarian surface epithelium and are common in Europe and the USA. One of the most famous studies on the subject reported that annual screening using CA125/transvaginal sonography (TVS) did not reduce the ovarian cancer mortality rate in the USA. In contrast, a recent study in the UK showed an overall average mortality reduction of 20% in the screening group. Another two studies further reported that the screening was associated with decreased stage at detection. Theoretically, annual screening using CA125/TVS could easily detect precursor lesions and could be more effective in Asia than in Europe and the USA. The detection of Type II ovarian carcinoma at an early stage remains an unresolved issue. The resolving power of CA125 or TVS screening alone is unlikely to be successful at resolving STICs. Biomarkers for the early detection of Type II carcinomas such as STICs need to be developed. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available

Other

Open AccessOpinion
A Resident’s Perspective of Ovarian Cancer
Diagnostics 2017, 7(2), 24; https://doi.org/10.3390/diagnostics7020024
Received: 5 January 2017 / Revised: 12 April 2017 / Accepted: 20 April 2017 / Published: 27 April 2017
Cited by 3 | PDF Full-text (381 KB) | HTML Full-text | XML Full-text
Abstract
Identifying, understanding, and curing disease is a lifelong endeavor for any medical practitioner. Equally as important is to be cognizant of the impact a disease has on the individual suffering from it, as well as on their family. Ovarian cancer is the leading [...] Read more.
Identifying, understanding, and curing disease is a lifelong endeavor for any medical practitioner. Equally as important is to be cognizant of the impact a disease has on the individual suffering from it, as well as on their family. Ovarian cancer is the leading cause of death from gynecologic malignancies. Symptoms are vague, and the disease is generally at an advanced stage at diagnosis. Efforts have been made to develop methods to identify ovarian cancer at earlier stages, thus improving overall mortality. Transvaginal ultrasound (TVUS), with and without laboratory tests, can be used to screen for ovarian cancer. For over thirty years, the University of Kentucky Markey Cancer Center Ovarian Cancer Screening Program has been studying the efficacy of TVUS for detecting early stage ovarian cancer. After 285,000+ TVUS examinations provided to over 45,000 women, the program has demonstrated that regular TVUS examinations can detect ovarian cancer at early stages, and that survival is increased in those women whose ovarian cancer was detected with screening and who undergo standard treatment. These results demonstrate the utility of TVUS as an efficacious method of ovarian cancer screening. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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Open AccessOpinion
A Perspective on Ovarian Cancer Biomarkers: Past, Present and Yet-To-Come
Diagnostics 2017, 7(1), 14; https://doi.org/10.3390/diagnostics7010014
Received: 7 January 2017 / Revised: 15 February 2017 / Accepted: 23 February 2017 / Published: 8 March 2017
Cited by 17 | PDF Full-text (495 KB) | HTML Full-text | XML Full-text
Abstract
The history of biomarkers and ultrasonography dates back over more than 50 years. The present status of biomarkers used in the context of ovarian cancer is addressed. Attention is given to new interpretations of the etiology of ovarian cancer. Cancer antigen 125 (CA125) [...] Read more.
The history of biomarkers and ultrasonography dates back over more than 50 years. The present status of biomarkers used in the context of ovarian cancer is addressed. Attention is given to new interpretations of the etiology of ovarian cancer. Cancer antigen 125 (CA125) and multivariate index assays (Ova1, Risk of Ovarian Malignancy Algorithm, Overa) are biomarker-driven considerations that are presented. Integration of biomarkers into ovarian cancer diagnostics and screening are presented in conjunction with ultrasound. Consideration is given to the serial application of both biomarkers and ultrasound, as well as morphology-based indices. Attempts are made to foresee how individualized molecular signatures may be able to both provide an alert of the potential for ovarian cancer and to provide molecular treatments tailored to a personalized genetic signature. In the future, an annual pelvic ultrasound and a comprehensive serum biomarker screening/diagnostic panel may replace the much maligned bimanual examination as part of the annual gynecologic examination. Taken together, it is likely that a new medical specialty for screening and early diagnostics will emerge for physicians and epidemiologists, a field of study that is independent of patient gender, organ, or the subspecialties of today. Full article
(This article belongs to the Special Issue Ovarian Cancer Screening) Printed Edition available
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