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Mona Saraiya - One of the best experts on this subject based on the ideXlab platform.
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national assessment of hpv and Pap Tests changes in cervical cancer screening national health interview survey
Preventive Medicine, 2017Co-Authors: Meg Watson, Vicki B Benard, Jessica B King, Anatasha Crawford, Mona SaraiyaAbstract:Abstract Background Major organizations recommend cytology screening (Pap Test) every 3 years for women aged 21–65; women aged 30 to 65 have the option of adding the HPV Test (co-Test) every 5 years. We examined national percentages of cervical cancer screening, and we examined use of co-Testing as an option for screening. Methods We used 2015 U.S. National Health Interview Survey (NHIS) data to examine recent cervical cancer screening (Pap Test within 3 years among women aged 21–65 without a hysterectomy; N = 10,596) and co-Testing (N = 9,125). We also conducted a multivariable analysis to determine odds of having had a Pap Test or co-Test by demographic variables. To evaluate changes in screening over time, we examined Pap Testing during the years 2000, 2005, 2008, 2010, 2013 and 2015. Analysis completed in Atlanta, GA during 2016. Results Overall, 81.1% of eligible women reported having a Pap Test within 3 years; percentages declined over time among all age groups. An estimated 14 million women aged 21–65 had not been screened within the past 3 years. Recent immigrants to the United States, women without insurance, and women without a usual source of healthcare had lower odds of being up to date with screening. About 1/3 of women up to date on Pap Testing reported having a co-Test with their most recent Pap Test. Conclusions Declines in screening among women aged 21–65 are cause for concern. More research is needed on co-Testing practices. Provider and patient education efforts may be needed to clarify recommended use of HPV Tests.
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abstract b92 hpv and Pap Test results among low income underserved women providing insights into management strategies
Cancer Epidemiology and Prevention Biomarkers, 2014Co-Authors: Mona Saraiya, Vicki B Benard, April Greek, Martin Steinau, Sonya Patel, George F Sawaya, Diane L Manninen, Stuart Massad, Elizabeth R UngerAbstract:Objective: Human Papillomavirus (HPV) DNA Testing combined with cytology (co-Testing) has been recommended as a primary cervical cancer screening strategy and will be covered as a preventive service by the Affordable Care Act (ACA). Women with discordant results (HPV positive/cytology negative) present significant management challenges and result in additional costs due to follow-up visits and Testing required. The frequency of discordant results in insured populations is at a level that does not negate the benefit of co-Testing. However, it is unknown if the frequency of discordant results would be the same for underserved women, who may have more risk factors for HPV infection and cancer precursors. Methods: The Centers for Disease Control and Prevention9s Cervical Cancer (Cx3) Study was conducted at 15 clinics in 6 Federally Qualified Health Centers (FQHCs) across Illinois. Providers at these clinics were given the option of co-Testing for routine cervical cancer screening. Clinical high-risk HPV Testing was performed using the FDA approved Hybrid Capture 2 assay (HC2: Qiagen). An additional research Test to determine type-specific HPV results was performed on residual extracts. Results: Testing was completed on 2246 underserved women, mean age 45.1 years. The HPV Test was positive in 7.2% and cytology abnormalities were detected in 6.0% with discordant results in 4.9% of women. The percentage of HPV positive Tests decreased with age, from 10.3% among 30-39 year olds to 4.5% among 50-60 year olds. Among women with negative normal Pap Test results who where high risk positive, 14% of the women were positive for HPV 16/18 while the remaining were positive for other high risk types. Conclusion: The rate of discordant co-Testing in this study of underserved women was similar to those reported throughout the U.S. in different populations, including those who are insured. Similarly, the lower percentage of discordant results and those positive for HPV 16/18 may favor a more conservative management strategy than an aggressive strategy of immediate colposcopy. Citation Format: Mona Saraiya, Vicki Benard, April Greek, Martin Steinau, Sonya Patel, Diane Manninen, George Sawaya, Stuart Massad, Elizabeth Unger. HPV and Pap Test results among low-income, underserved women: Providing insights into management strategies. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B92. doi:10.1158/1538-7755.DISP13-B92
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type specific hpv and Pap Test results among low income underserved women providing insights into management strategies
American Journal of Obstetrics and Gynecology, 2014Co-Authors: Mona Saraiya, Vicki B Benard, April Greek, Martin Steinau, Sonya Patel, Stewart L Massad, George F Sawaya, Elizabeth R UngerAbstract:Objective The primary cervical cancer screening strategy for women over age 30 is high-risk human Papillomavirus (HPV) Testing combined with Papanicolaou (Pap) Testing (coTesting) every 5 years. This combination strategy is a preventive service that is required by the Affordable Care Act to be covered with no cost-sharing by most health insurance plans. The coTesting recommendation was made based entirely on prospective data from an insured population that may have a lower proportion of women with HPV positive and Pap negative results (ie, discordant results). The discordant group represents a very difficult group to manage. If the frequency of discordant results among underserved women is higher, health care providers may perceive the coTesting strategy to be a less favorable screening strategy than traditional Pap Testing every 3 years. Study Design The Centers for Disease Control and Prevention's Cervical Cancer Study was conducted at 15 clinics in 6 federally qualified health centers across Illinois. Providers at these clinics were given the option of coTesting for routine cervical cancer screening. Type-specific HPV detection was performed on residual extracts using linear array. Results Pap Test results were abnormal in 6.0% and HPV was positive in 7.2% of the underserved women screened in this study (mean age, 45.1 years). HPV prevalence decreased with age, from 10.3% among 30- to 39-year-olds to 4.5% among 50- to 60-year-olds. About 5% of the women had a combination of a positive HPV Test and normal Pap Test results; HPV 16/18 was identified in 14% of discordant women. Conclusion The rate of discordant results among underserved women was similar to those reported throughout the US in a variety of populations. Typing for HPV 16/18 appears to assist in the management in a small proportion of women with discordant results.
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why the Pap Test awareness and use of the Pap Test among women in the united states
Journal of Womens Health, 2011Co-Authors: Nikki A Hawkins, Crystale Purvis Cooper, Mona Saraiya, Cynthia A Gelb, Lindsey PolonecAbstract:Abstract Objective: To inform campaign development by assessing awareness, previous receipt, and knowledge of the purpose of Papanicolaou (Pap) Testing among women aged ≥18 years and to identify differences in awareness, receipt, and knowledge by demographic characteristics. Methods: Data were analyzed from the 2008 HealthStyles survey, an annual mail survey conducted in the United States covering trends in health-related behavior. Women were asked questions on awareness, past use, and knowledge of the purpose of the Pap Test and other gynecologic Tests and procedures; 2991 women participated. Results: Although 96.7% of the women had heard of and 93.0% reported having received a Pap Test, these proportions were lower among those who were 18–34 years old and among those who had lower levels of education and income. Over 80% knew the Pap Test was used to screen for cervical cancer, but 63.3% believed it also was used to screen for vaginal cancer (44.9%), sexually transmitted diseases (STDs) other than human...
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cervical cancer screening with both human Papillomavirus and Papanicolaou Testing vs Papanicolaou Testing alone what screening intervals are physicians recommending
JAMA Internal Medicine, 2010Co-Authors: Mona Saraiya, Robin K Yabroff, Zahava Berkowitz, Louise Wideroff, Sarah Kobrin, Vicki B BenardAbstract: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.
Amy P.n. Skubitz - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the potential of Pap Test fluid and cervical swabs to serve as clinical diagnostic biospecimens for the detection of ovarian cancer by mass spectrometry-based proteomics
Clinical Proteomics, 2021Co-Authors: Kristin L.m. Boylan, Melissa A. Geller, Peter A. Argenta, Timothy J. Griffin, Somaieh Afiuni-zadeh, Amy P.n. SkubitzAbstract:Background The purpose of this study was to determine whether the residual fixative from a liquid-based Pap Test or a swab of the cervix contained proteins that were also found in the primary tumor of a woman with high grade serous ovarian cancer. This study is the first step in determining the feasibility of using the liquid-based Pap Test or a cervical swab for the detection of ovarian cancer protein biomarkers. Methods Proteins were concentrated by acetone precipitation from the cell-free supernatant of the liquid-based Pap Test fixative or eluted from the cervical swab. Protein was also extracted from the patient’s tumor tissue. The protein samples were digested into peptides with trypsin, then the peptides were run on 2D-liquid chromatography mass spectrometry (2D-LCMS). The data was searched against a human protein database for the identification of peptides and proteins in each biospecimen. The proteins that were identified were classified for cellular localization and molecular function by bioinformatics integration. Results We identified almost 5000 proteins total in the three matched biospecimens. More than 2000 proteins were expressed in each of the three biospecimens, including several known ovarian cancer biomarkers such as CA125, HE4, and mesothelin. By Scaffold analysis of the protein Gene Ontology categories and functional analysis using PANTHER, the proteins were classified by cellular localization and molecular function, demonstrating that the Pap Test fluid and cervical swab proteins are similar to each other, and also to the tumor extract. Conclusions Our results suggest that Pap Test fixatives and cervical swabs are a rich source of tumor-specific biomarkers for ovarian cancer, which could be developed as a Test for ovarian cancer detection.
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abstract dp 002 comparison of potential ovarian cancer biomarkers by mass spectrometry based proteomic analysis of residual Pap Test fluid cervical swabs and tumor tissue from an ovarian cancer patient
Clinical Cancer Research, 2019Co-Authors: Kristin L.m. Boylan, Melissa A. Geller, Peter A. Argenta, Timothy J. Griffin, Anna C Rogers, Amy P.n. SkubitzAbstract:Early detection is the key to increased survival for women with ovarian cancer, yet a screening tool has yet to be developed that is adequately sensitive and specific enough for use in the general population. In contrast, screening for cervical cancer by Pap Tests has been routinely performed for over 50 years. In the liquid-based Pap Test, cells are collected from the cervix and placed into an alcohol-based fixative and then examined for abnormal cells. Since ovarian cancer cells have been observed in Pap Tests, we reasoned that ovarian cancer peptide biomarkers may also be present. Our central hypothesis is that proteins shed by ovarian cancer cells can be detected during routine Pap Tests by mass spectrometry (MS)-based proteomics. In particular, when collected at the time of cervical cancer Pap Test screening, the alcohol-based Pap Test fixative and cervical swabs are ideal for biomarker discovery since they are derived from a site near the ovarian cancer (i.e. proteins may be secreted or shed from the tumor and flow through the fallopian tube into the uterus and out the cervical opening). Recently, the fimbria of the fallopian tube have been suggested to be the true precursor to ovarian cancer, strengthening our hypothesis that ovarian cancer proteins will be found in the lower genital tract, perhaps even at early stages. To demonstrate the feasibility of using Pap Tests as a biospecimen for proteomics, we previously examined the proteins present in residual Pap Test fixative samples from women with normal cervical cytology by MS and described 152 proteins in the “Normal Pap Proteome.” The objective of this study was to identify and compare the proteins from three different sources from the same ovarian cancer patient: (i) the residual Pap Test fixative, (ii) a Merocel swab of the cervix, and (iii) the primary ovarian cancer tumor tissue. Proteins were concentrated from the cell-free supernatant of the Pap Test fixative or eluted from the swab, and then trypsin digested using the filter-aided sample preparation method. A total protein extract from the patient9s tumor tissue was digested by standard in-solution trypsin digestion. The samples were run on 2D-liquid chromatography MS/MS, followed by bioinformatics integration. We identified over 5000 proteins total in the three samples. More than 2000 proteins were expressed in all three ovarian cancer samples, including several known ovarian cancer biomarkers such as CA125. By Scaffold analysis of the Gene Ontology nomenclature of the proteins, we classified the proteins by both cellular localization and biological processes. Additional matched samples from patients will be used to build a library of proteins and peptides that are specific to ovarian cancer for use in the development of targeted MS assays. We conclude that quantification of proteins from Pap Test fixatives and cervical swabs will prove to be a rich source of biomarkers for ovarian cancer detection. Citation Format: Kristin L.M. Boylan, Anna C. Rogers, Melissa A. Geller, Peter A. Argenta, Timothy J. Griffin, and Amy P.N. Skubitz. COMPARISON OF POTENTIAL OVARIAN CANCER BIOMARKERS BY MASS SPECTROMETRY-BASED PROTEOMIC ANALYSIS OF RESIDUAL Pap Test FLUID, CERVICAL SWABS, AND TUMOR TISSUE FROM AN OVARIAN CANCER PATIENT [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-002.
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evaluating the potential of residual Pap Test fluid as a resource for the metaproteomic analysis of the cervical vaginal microbiome
Scientific Reports, 2018Co-Authors: Somaieh Afiunizadeh, Kristin L.m. Boylan, Timothy J. Griffin, Pratik D Jagtap, Joel D Rudney, Marnie L Peterson, Amy P.n. SkubitzAbstract:The human cervical-vaginal area contains proteins derived from microorganisms that may prevent or predispose women to gynecological conditions. The liquid Pap Test fixative is an unexplored resource for analysis of microbial communities and the microbe-host interaction. Previously, we showed that the residual cell-free fixative from discarded Pap Tests of healthy women could be used for mass spectrometry (MS) based proteomic identification of cervical-vaginal proteins. In this study, we reprocessed these MS raw data files for metaproteomic analysis to characterize the microbial community composition and function of microbial proteins in the cervical-vaginal region. This was accomplished by developing a customized protein sequence database encompassing microbes likely present in the vagina. High-mass accuracy data were searched against the protein FASTA database using a two-step search method within the Galaxy for proteomics platform. Data was analyzed by MEGAN6 (MetaGenomeAnalyzer) for phylogenetic and functional characterization. We identified over 300 unique peptides from a variety of bacterial phyla and Candida. Peptides corresponding to proteins involved in carbohydrate metabolism, oxidation-reduction, and transport were identified. By identifying microbial peptides in Pap Test supernatants it may be possible to acquire a functional signature of these microbes, as well as detect specific proteins associated with cervical health and disease.
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Abstract B34: Tandem Mass Tag 10-plex isobaric labeling of Pap Test proteins: A novel method for the identification of ovarian cancer protein biomarkers by mass spectrometry.
Prevention Screening Early Diagnostics and Epidemiology, 2016Co-Authors: Amy P.n. Skubitz, Somi Afiuni, Kristin L.m. Boylan, Melissa A. Geller, Peter A. Argenta, Samantha Hoffman, Timothy J. GriffinAbstract:Early detection is the key to increased survival for women with ovarian cancer, yet a screening tool has yet to be developed that is adequately sensitive and specific enough for use in the general population. A need also exists for a reliable diagnostic method for women who present with an abdominal mass. In contrast, screening for cervical cancer by Pap Tests has been routinely performed for over 50 years. In the liquid-based Pap Test, cells are collected from the cervical os and placed into an alcohol-based fixative and then examined for abnormal cells. Since ovarian cancer cells have been observed in Pap Tests, we reasoned that ovarian cancer peptide biomarkers may also be present. Our central hypothesis is that proteins shed by ovarian cancer cells can be detected in the Pap Test fixative by Mass Spectrometry (MS)-based proteomics. The Pap Test fixative is ideal for biomarker discovery since it is derived from a site near the ovarian cancer (i.e. proteins may be secreted or shed from the tumor and flow through the fallopian tube into the uterus and out the cervical opening). Recently, the fimbria of the fallopian tube have been suggested to be the true precursor to ovarian cancer, strengthening our hypothesis that ovarian cancer proteins will be found in the lower genital tract, perhaps even at early stages. To demonstrate the feasibility of this approach, we previously examined the proteins present in residual Pap Test fixative samples from women with normal cervical cytology by MS, and described 152 proteins in the “Normal Pap Proteome.” (Boylan et al., Clinical Proteomics, 2014). The objective of this study is to discover ovarian cancer biomarkers in Pap Test fixative samples by MS-based proteomic techniques. We used isobaric tags to quantify the proteins in liquid Pap Test samples from women with ovarian cancer compared to women with benign gynecological disease and healthy women. Proteins were concentrated from “Mock” Pap Tests, and samples were trypsin digested utilizing the STrap technique to increase the likelihood that proteins would be recovered. We then performed Tandem Mass Tag™ (TMT) 10-plex labeling of Pap Test fixative samples from post-menopausal women: 3 with ovarian cancer, 3 with benign gynecological conditions, 3 healthy, and a Reference Control consisting of pooled samples. The 10 labeled samples were combined and run on 2D LC-MS/MS, followed by bioinformatics integration to discover proteins in Pap Test fixatives that are unique and/or differentially expressed in the samples. We identified >3800 proteins total, and 22 proteins that were expressed at least 2-fold higher in all three ovarian cancer samples compared to the controls. We conclude that quantification of proteins from Pap Test samples will prove a rich source of biomarkers for ovarian cancer detection. Citation Format: Amy P.N. Skubitz, Somi Afiuni, Kristin L.M. Boylan, Melissa Geller, Peter Argenta, Samantha Hoffman, Timothy Griffin. Tandem Mass Tag 10-plex isobaric labeling of Pap Test proteins: A novel method for the identification of ovarian cancer protein biomarkers by mass spectrometry. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B34.
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a feasibility study to identify proteins in the residual Pap Test fluid of women with normal cytology by mass spectrometry based proteomics
Clinical Proteomics, 2014Co-Authors: Kristin L.m. Boylan, Melissa A. Geller, Timothy J. Griffin, Somaieh Afiunizadeh, Kayla Hickey, Stefan E Pambuccian, Amy P.n. SkubitzAbstract:Background The proteomic analysis of body fluids is a growing technology for the identification of protein biomarkers of disease. Given that Papanicolaou Tests (Pap Tests) are routinely performed on over 30 million women annually in the U.S. to screen for cervical cancer, we examined the residual Pap Test fluid as a source of protein for analysis by mass spectrometry (MS). In the liquid-based Pap Test, cervical cells are collected from the ectocervix and placed into an alcohol-based fixative prior to staining and pathologic examination. We hypothesized that proteins shed by cells of the female genital tract can be detected in the Pap Test fixative by MS-based proteomic techniques. We examined the feasibility of using residual fluid from discarded Pap Tests with cytologically “normal” results to optimize sample preparation for MS analysis. The protein composition of the cell-free Pap Test fluid was determined by silver staining of sodium dodecyl sulfate -polyacrylamide gels, and the abundance of serum proteins was examined by Western immunoblot using an antibody against human serum albumin. Both pooled and individual samples were trypsin digested and analyzed by two-dimensional MS/MS. Proteins were identified by searching against the Human Uniprot database, and characterized for localization, function and relative abundance.
Kristin L.m. Boylan - One of the best experts on this subject based on the ideXlab platform.
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Evaluation of the potential of Pap Test fluid and cervical swabs to serve as clinical diagnostic biospecimens for the detection of ovarian cancer by mass spectrometry-based proteomics
Clinical Proteomics, 2021Co-Authors: Kristin L.m. Boylan, Melissa A. Geller, Peter A. Argenta, Timothy J. Griffin, Somaieh Afiuni-zadeh, Amy P.n. SkubitzAbstract:Background The purpose of this study was to determine whether the residual fixative from a liquid-based Pap Test or a swab of the cervix contained proteins that were also found in the primary tumor of a woman with high grade serous ovarian cancer. This study is the first step in determining the feasibility of using the liquid-based Pap Test or a cervical swab for the detection of ovarian cancer protein biomarkers. Methods Proteins were concentrated by acetone precipitation from the cell-free supernatant of the liquid-based Pap Test fixative or eluted from the cervical swab. Protein was also extracted from the patient’s tumor tissue. The protein samples were digested into peptides with trypsin, then the peptides were run on 2D-liquid chromatography mass spectrometry (2D-LCMS). The data was searched against a human protein database for the identification of peptides and proteins in each biospecimen. The proteins that were identified were classified for cellular localization and molecular function by bioinformatics integration. Results We identified almost 5000 proteins total in the three matched biospecimens. More than 2000 proteins were expressed in each of the three biospecimens, including several known ovarian cancer biomarkers such as CA125, HE4, and mesothelin. By Scaffold analysis of the protein Gene Ontology categories and functional analysis using PANTHER, the proteins were classified by cellular localization and molecular function, demonstrating that the Pap Test fluid and cervical swab proteins are similar to each other, and also to the tumor extract. Conclusions Our results suggest that Pap Test fixatives and cervical swabs are a rich source of tumor-specific biomarkers for ovarian cancer, which could be developed as a Test for ovarian cancer detection.
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abstract dp 002 comparison of potential ovarian cancer biomarkers by mass spectrometry based proteomic analysis of residual Pap Test fluid cervical swabs and tumor tissue from an ovarian cancer patient
Clinical Cancer Research, 2019Co-Authors: Kristin L.m. Boylan, Melissa A. Geller, Peter A. Argenta, Timothy J. Griffin, Anna C Rogers, Amy P.n. SkubitzAbstract:Early detection is the key to increased survival for women with ovarian cancer, yet a screening tool has yet to be developed that is adequately sensitive and specific enough for use in the general population. In contrast, screening for cervical cancer by Pap Tests has been routinely performed for over 50 years. In the liquid-based Pap Test, cells are collected from the cervix and placed into an alcohol-based fixative and then examined for abnormal cells. Since ovarian cancer cells have been observed in Pap Tests, we reasoned that ovarian cancer peptide biomarkers may also be present. Our central hypothesis is that proteins shed by ovarian cancer cells can be detected during routine Pap Tests by mass spectrometry (MS)-based proteomics. In particular, when collected at the time of cervical cancer Pap Test screening, the alcohol-based Pap Test fixative and cervical swabs are ideal for biomarker discovery since they are derived from a site near the ovarian cancer (i.e. proteins may be secreted or shed from the tumor and flow through the fallopian tube into the uterus and out the cervical opening). Recently, the fimbria of the fallopian tube have been suggested to be the true precursor to ovarian cancer, strengthening our hypothesis that ovarian cancer proteins will be found in the lower genital tract, perhaps even at early stages. To demonstrate the feasibility of using Pap Tests as a biospecimen for proteomics, we previously examined the proteins present in residual Pap Test fixative samples from women with normal cervical cytology by MS and described 152 proteins in the “Normal Pap Proteome.” The objective of this study was to identify and compare the proteins from three different sources from the same ovarian cancer patient: (i) the residual Pap Test fixative, (ii) a Merocel swab of the cervix, and (iii) the primary ovarian cancer tumor tissue. Proteins were concentrated from the cell-free supernatant of the Pap Test fixative or eluted from the swab, and then trypsin digested using the filter-aided sample preparation method. A total protein extract from the patient9s tumor tissue was digested by standard in-solution trypsin digestion. The samples were run on 2D-liquid chromatography MS/MS, followed by bioinformatics integration. We identified over 5000 proteins total in the three samples. More than 2000 proteins were expressed in all three ovarian cancer samples, including several known ovarian cancer biomarkers such as CA125. By Scaffold analysis of the Gene Ontology nomenclature of the proteins, we classified the proteins by both cellular localization and biological processes. Additional matched samples from patients will be used to build a library of proteins and peptides that are specific to ovarian cancer for use in the development of targeted MS assays. We conclude that quantification of proteins from Pap Test fixatives and cervical swabs will prove to be a rich source of biomarkers for ovarian cancer detection. Citation Format: Kristin L.M. Boylan, Anna C. Rogers, Melissa A. Geller, Peter A. Argenta, Timothy J. Griffin, and Amy P.N. Skubitz. COMPARISON OF POTENTIAL OVARIAN CANCER BIOMARKERS BY MASS SPECTROMETRY-BASED PROTEOMIC ANALYSIS OF RESIDUAL Pap Test FLUID, CERVICAL SWABS, AND TUMOR TISSUE FROM AN OVARIAN CANCER PATIENT [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-002.
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evaluating the potential of residual Pap Test fluid as a resource for the metaproteomic analysis of the cervical vaginal microbiome
Scientific Reports, 2018Co-Authors: Somaieh Afiunizadeh, Kristin L.m. Boylan, Timothy J. Griffin, Pratik D Jagtap, Joel D Rudney, Marnie L Peterson, Amy P.n. SkubitzAbstract:The human cervical-vaginal area contains proteins derived from microorganisms that may prevent or predispose women to gynecological conditions. The liquid Pap Test fixative is an unexplored resource for analysis of microbial communities and the microbe-host interaction. Previously, we showed that the residual cell-free fixative from discarded Pap Tests of healthy women could be used for mass spectrometry (MS) based proteomic identification of cervical-vaginal proteins. In this study, we reprocessed these MS raw data files for metaproteomic analysis to characterize the microbial community composition and function of microbial proteins in the cervical-vaginal region. This was accomplished by developing a customized protein sequence database encompassing microbes likely present in the vagina. High-mass accuracy data were searched against the protein FASTA database using a two-step search method within the Galaxy for proteomics platform. Data was analyzed by MEGAN6 (MetaGenomeAnalyzer) for phylogenetic and functional characterization. We identified over 300 unique peptides from a variety of bacterial phyla and Candida. Peptides corresponding to proteins involved in carbohydrate metabolism, oxidation-reduction, and transport were identified. By identifying microbial peptides in Pap Test supernatants it may be possible to acquire a functional signature of these microbes, as well as detect specific proteins associated with cervical health and disease.
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Abstract B34: Tandem Mass Tag 10-plex isobaric labeling of Pap Test proteins: A novel method for the identification of ovarian cancer protein biomarkers by mass spectrometry.
Prevention Screening Early Diagnostics and Epidemiology, 2016Co-Authors: Amy P.n. Skubitz, Somi Afiuni, Kristin L.m. Boylan, Melissa A. Geller, Peter A. Argenta, Samantha Hoffman, Timothy J. GriffinAbstract:Early detection is the key to increased survival for women with ovarian cancer, yet a screening tool has yet to be developed that is adequately sensitive and specific enough for use in the general population. A need also exists for a reliable diagnostic method for women who present with an abdominal mass. In contrast, screening for cervical cancer by Pap Tests has been routinely performed for over 50 years. In the liquid-based Pap Test, cells are collected from the cervical os and placed into an alcohol-based fixative and then examined for abnormal cells. Since ovarian cancer cells have been observed in Pap Tests, we reasoned that ovarian cancer peptide biomarkers may also be present. Our central hypothesis is that proteins shed by ovarian cancer cells can be detected in the Pap Test fixative by Mass Spectrometry (MS)-based proteomics. The Pap Test fixative is ideal for biomarker discovery since it is derived from a site near the ovarian cancer (i.e. proteins may be secreted or shed from the tumor and flow through the fallopian tube into the uterus and out the cervical opening). Recently, the fimbria of the fallopian tube have been suggested to be the true precursor to ovarian cancer, strengthening our hypothesis that ovarian cancer proteins will be found in the lower genital tract, perhaps even at early stages. To demonstrate the feasibility of this approach, we previously examined the proteins present in residual Pap Test fixative samples from women with normal cervical cytology by MS, and described 152 proteins in the “Normal Pap Proteome.” (Boylan et al., Clinical Proteomics, 2014). The objective of this study is to discover ovarian cancer biomarkers in Pap Test fixative samples by MS-based proteomic techniques. We used isobaric tags to quantify the proteins in liquid Pap Test samples from women with ovarian cancer compared to women with benign gynecological disease and healthy women. Proteins were concentrated from “Mock” Pap Tests, and samples were trypsin digested utilizing the STrap technique to increase the likelihood that proteins would be recovered. We then performed Tandem Mass Tag™ (TMT) 10-plex labeling of Pap Test fixative samples from post-menopausal women: 3 with ovarian cancer, 3 with benign gynecological conditions, 3 healthy, and a Reference Control consisting of pooled samples. The 10 labeled samples were combined and run on 2D LC-MS/MS, followed by bioinformatics integration to discover proteins in Pap Test fixatives that are unique and/or differentially expressed in the samples. We identified >3800 proteins total, and 22 proteins that were expressed at least 2-fold higher in all three ovarian cancer samples compared to the controls. We conclude that quantification of proteins from Pap Test samples will prove a rich source of biomarkers for ovarian cancer detection. Citation Format: Amy P.N. Skubitz, Somi Afiuni, Kristin L.M. Boylan, Melissa Geller, Peter Argenta, Samantha Hoffman, Timothy Griffin. Tandem Mass Tag 10-plex isobaric labeling of Pap Test proteins: A novel method for the identification of ovarian cancer protein biomarkers by mass spectrometry. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B34.
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a feasibility study to identify proteins in the residual Pap Test fluid of women with normal cytology by mass spectrometry based proteomics
Clinical Proteomics, 2014Co-Authors: Kristin L.m. Boylan, Melissa A. Geller, Timothy J. Griffin, Somaieh Afiunizadeh, Kayla Hickey, Stefan E Pambuccian, Amy P.n. SkubitzAbstract:Background The proteomic analysis of body fluids is a growing technology for the identification of protein biomarkers of disease. Given that Papanicolaou Tests (Pap Tests) are routinely performed on over 30 million women annually in the U.S. to screen for cervical cancer, we examined the residual Pap Test fluid as a source of protein for analysis by mass spectrometry (MS). In the liquid-based Pap Test, cervical cells are collected from the ectocervix and placed into an alcohol-based fixative prior to staining and pathologic examination. We hypothesized that proteins shed by cells of the female genital tract can be detected in the Pap Test fixative by MS-based proteomic techniques. We examined the feasibility of using residual fluid from discarded Pap Tests with cytologically “normal” results to optimize sample preparation for MS analysis. The protein composition of the cell-free Pap Test fluid was determined by silver staining of sodium dodecyl sulfate -polyacrylamide gels, and the abundance of serum proteins was examined by Western immunoblot using an antibody against human serum albumin. Both pooled and individual samples were trypsin digested and analyzed by two-dimensional MS/MS. Proteins were identified by searching against the Human Uniprot database, and characterized for localization, function and relative abundance.
Christina S Kong - One of the best experts on this subject based on the ideXlab platform.
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utility of p16 immunohistochemistry in evaluating negative cervical biopsies following high risk Pap Test results
The American Journal of Surgical Pathology, 2017Co-Authors: Alana F Shain, Shirley Kwok, Ann K Folkins, Christina S KongAbstract:The Lower Anogenital Squamous Terminology (LAST) Standardization Project for human Papilloma virus (HPV)-associated lesions specifically recommends the use of p16 immunohistochemistry (IHC) as an adjunct to morphologic assessment of cervical biopsies interpreted as negative or low-grade squamous intraepithelial lesion (LSIL) from patients with prior high-risk Pap Test results (high-grade squamous intraepithelial lesion [HSIL], atypical squamous cells cannot exclude HSIL, atypical glandular cells [AGC], or HPV16 atypical squamous cells of undetermined significance [ASC-US]). The impetus for this recommendation is to increase detection of missed high-grade disease. However, the quality of evidence supporting this recommendation was lower than that for the other LAST recommendations addressing improved consistency in the diagnosis of HSIL with the use of p16. A database search spanning 10 years identified 341 cases (encompassing 736 discrete biopsy specimens) interpreted as negative for dysplasia from 330 patients with a prior high-risk Pap result (atypical squamous cells cannot exclude HSIL, HSIL, atypical glandular cells, not otherwise specified [AGC-NOS], atypical endocervical cells--NOS [AEC-NOS], and AEC-favor neoplastic). p16 IHC was performed and detected missed abnormalities in 11/341 (3.2%) cases. The abnormalities corresponded to missed foci of HSIL (cervical intraepithelial neoplasia [CIN] 2) (n=1), SIL-indeterminate grade (n=7), atypical squamous metaplasia (n=2), and LSIL [CIN1]) (n=1). Subsequent histologic follow-up identified HSIL or greater in 6/8 (75%) p16 cases versus 20/79 (25.3%) p16 cases (P=0.0079). p16 IHC performed on biopsies interpreted as negative from patients with prior high-risk Pap Test results increased the detection rate of missed SIL. A p16 result also significantly increased the likelihood of HSIL on subsequent biopsy. Although further studies are required to determine what percentage of missed HSIL justifies the additional cost, improved detection of HSIL in high-risk patients may lead to fewer diagnostic procedures and fewer patients lost to follow-up.
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abstract 433 utility of p16 immunohistochemistry in evaluating negative cervical biopsies following high risk Pap Test results
Cancer Research, 2016Co-Authors: Alana F Shain, Shirley Kwok, Ann K Folkins, Christina S KongAbstract:The Lower Anogenital Squamous Terminology (LAST) Standardization Project for HPV-associated Lesions recommends the use of p16 immunohistochemistry as an adjunct to morphologic assessment of cervical biopsies interpreted as negative from patients that are at high risk for missed high-grade disease (defined as a prior cytologic interpretation of HSIL, ASC-H, ASC-US/HPV-16+, or AGC-NOS) (Darragh et al., 2012). However, few studies have specifically evaluated the utility of performing p16 on negative cervical biopsies and endocervical curettage specimens following high-risk Pap Test results. A search of the Stanford Cytopathology database from 7/1/2002-6/30/2012 for cervical cytology cases with diagnoses of ASC-H, HSIL, AGC-NOS, and atypical endocervical cells NOS (AGC-EC) yielded 1517 cases. Of these, 703 cases had histologic follow-up. Biopsies were excluded if diagnosed as atypical, low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), or insufficient, or if the time to follow up was greater than 1 year. Immunostain for p16 (CINtec) was performed on 350 cases from 339 patients (age 16-85 yrs, average 42+/-14) and scored as positive (diffuse strong), negative or equivocal. 6 cases were excluded due to insufficient tissue and 3 cases with equivocal staining were excluded from further analysis. For p16(+) and equivocal cases, HPV in situ hybridization (ISH) (Ventana HPV III Family 16 probe) was performed and the corresponding HE 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 433.
Vicki B Benard - One of the best experts on this subject based on the ideXlab platform.
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national assessment of hpv and Pap Tests changes in cervical cancer screening national health interview survey
Preventive Medicine, 2017Co-Authors: Meg Watson, Vicki B Benard, Jessica B King, Anatasha Crawford, Mona SaraiyaAbstract:Abstract Background Major organizations recommend cytology screening (Pap Test) every 3 years for women aged 21–65; women aged 30 to 65 have the option of adding the HPV Test (co-Test) every 5 years. We examined national percentages of cervical cancer screening, and we examined use of co-Testing as an option for screening. Methods We used 2015 U.S. National Health Interview Survey (NHIS) data to examine recent cervical cancer screening (Pap Test within 3 years among women aged 21–65 without a hysterectomy; N = 10,596) and co-Testing (N = 9,125). We also conducted a multivariable analysis to determine odds of having had a Pap Test or co-Test by demographic variables. To evaluate changes in screening over time, we examined Pap Testing during the years 2000, 2005, 2008, 2010, 2013 and 2015. Analysis completed in Atlanta, GA during 2016. Results Overall, 81.1% of eligible women reported having a Pap Test within 3 years; percentages declined over time among all age groups. An estimated 14 million women aged 21–65 had not been screened within the past 3 years. Recent immigrants to the United States, women without insurance, and women without a usual source of healthcare had lower odds of being up to date with screening. About 1/3 of women up to date on Pap Testing reported having a co-Test with their most recent Pap Test. Conclusions Declines in screening among women aged 21–65 are cause for concern. More research is needed on co-Testing practices. Provider and patient education efforts may be needed to clarify recommended use of HPV Tests.
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abstract b92 hpv and Pap Test results among low income underserved women providing insights into management strategies
Cancer Epidemiology and Prevention Biomarkers, 2014Co-Authors: Mona Saraiya, Vicki B Benard, April Greek, Martin Steinau, Sonya Patel, George F Sawaya, Diane L Manninen, Stuart Massad, Elizabeth R UngerAbstract:Objective: Human Papillomavirus (HPV) DNA Testing combined with cytology (co-Testing) has been recommended as a primary cervical cancer screening strategy and will be covered as a preventive service by the Affordable Care Act (ACA). Women with discordant results (HPV positive/cytology negative) present significant management challenges and result in additional costs due to follow-up visits and Testing required. The frequency of discordant results in insured populations is at a level that does not negate the benefit of co-Testing. However, it is unknown if the frequency of discordant results would be the same for underserved women, who may have more risk factors for HPV infection and cancer precursors. Methods: The Centers for Disease Control and Prevention9s Cervical Cancer (Cx3) Study was conducted at 15 clinics in 6 Federally Qualified Health Centers (FQHCs) across Illinois. Providers at these clinics were given the option of co-Testing for routine cervical cancer screening. Clinical high-risk HPV Testing was performed using the FDA approved Hybrid Capture 2 assay (HC2: Qiagen). An additional research Test to determine type-specific HPV results was performed on residual extracts. Results: Testing was completed on 2246 underserved women, mean age 45.1 years. The HPV Test was positive in 7.2% and cytology abnormalities were detected in 6.0% with discordant results in 4.9% of women. The percentage of HPV positive Tests decreased with age, from 10.3% among 30-39 year olds to 4.5% among 50-60 year olds. Among women with negative normal Pap Test results who where high risk positive, 14% of the women were positive for HPV 16/18 while the remaining were positive for other high risk types. Conclusion: The rate of discordant co-Testing in this study of underserved women was similar to those reported throughout the U.S. in different populations, including those who are insured. Similarly, the lower percentage of discordant results and those positive for HPV 16/18 may favor a more conservative management strategy than an aggressive strategy of immediate colposcopy. Citation Format: Mona Saraiya, Vicki Benard, April Greek, Martin Steinau, Sonya Patel, Diane Manninen, George Sawaya, Stuart Massad, Elizabeth Unger. HPV and Pap Test results among low-income, underserved women: Providing insights into management strategies. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B92. doi:10.1158/1538-7755.DISP13-B92
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type specific hpv and Pap Test results among low income underserved women providing insights into management strategies
American Journal of Obstetrics and Gynecology, 2014Co-Authors: Mona Saraiya, Vicki B Benard, April Greek, Martin Steinau, Sonya Patel, Stewart L Massad, George F Sawaya, Elizabeth R UngerAbstract:Objective The primary cervical cancer screening strategy for women over age 30 is high-risk human Papillomavirus (HPV) Testing combined with Papanicolaou (Pap) Testing (coTesting) every 5 years. This combination strategy is a preventive service that is required by the Affordable Care Act to be covered with no cost-sharing by most health insurance plans. The coTesting recommendation was made based entirely on prospective data from an insured population that may have a lower proportion of women with HPV positive and Pap negative results (ie, discordant results). The discordant group represents a very difficult group to manage. If the frequency of discordant results among underserved women is higher, health care providers may perceive the coTesting strategy to be a less favorable screening strategy than traditional Pap Testing every 3 years. Study Design The Centers for Disease Control and Prevention's Cervical Cancer Study was conducted at 15 clinics in 6 federally qualified health centers across Illinois. Providers at these clinics were given the option of coTesting for routine cervical cancer screening. Type-specific HPV detection was performed on residual extracts using linear array. Results Pap Test results were abnormal in 6.0% and HPV was positive in 7.2% of the underserved women screened in this study (mean age, 45.1 years). HPV prevalence decreased with age, from 10.3% among 30- to 39-year-olds to 4.5% among 50- to 60-year-olds. About 5% of the women had a combination of a positive HPV Test and normal Pap Test results; HPV 16/18 was identified in 14% of discordant women. Conclusion The rate of discordant results among underserved women was similar to those reported throughout the US in a variety of populations. Typing for HPV 16/18 appears to assist in the management in a small proportion of women with discordant results.
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cervical cancer screening with both human Papillomavirus and Papanicolaou Testing vs Papanicolaou Testing alone what screening intervals are physicians recommending
JAMA Internal Medicine, 2010Co-Authors: Mona Saraiya, Robin K Yabroff, Zahava Berkowitz, Louise Wideroff, Sarah Kobrin, Vicki B BenardAbstract: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.
