Global Coalition Against Cervical Cancer

Arlington, VA, United States

Global Coalition Against Cervical Cancer

Arlington, VA, United States

Time filter

Source Type

Campos N.G.,Center for Health Decision Science | Castle P.E.,Global Coalition Against Cervical Cancer | Castle P.E.,Yeshiva University | Wright T.C.,Columbia University | Kim J.J.,Center for Health Decision Science
International Journal of Cancer | Year: 2015

As cervical cancer screening programs are implemented in low-resource settings, protocols are needed to maximize health benefits under operational constraints. Our objective was to develop a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage and follow-up of screen-positive women, to help decision makers identify where program investments yield the greatest value. As an illustrative example, we used an individual-based Monte Carlo simulation model of the natural history of human papillomavirus (HPV) and cervical cancer calibrated to epidemiologic data from Uganda. We assumed once in a lifetime screening at age 35 with two-visit HPV DNA testing or one-visit visual inspection with acetic acid (VIA). We assessed the health and economic tradeoffs that arise between (i) test sensitivity and screening coverage; (ii) test sensitivity and loss to follow-up (LTFU) of screen-positive women; and (iii) test sensitivity, screening coverage and LTFU simultaneously. The decline in health benefits associated with sacrificing HPV DNA test sensitivity by 20% (e.g., shifting from provider- to self-collection of specimens) could be offset by gains in coverage if coverage increased by at least 20%. When LTFU was 10%, two-visit HPV DNA testing with 80-90% sensitivity was more effective and more cost-effective than one-visit VIA with 40% sensitivity and yielded greater health benefits than VIA even as VIA sensitivity increased to 60% and HPV test sensitivity declined to 70%. As LTFU increased, two-visit HPV DNA testing became more costly and less effective than one-visit VIA. Setting-specific data on achievable test sensitivity, coverage, follow-up rates and programmatic costs are needed to guide decision making for cervical cancer screening. What's new? Cervical cancer is a leading cause of cancer death among women worldwide, despite the fact that the disease is preventable through screening programs. While routine screening with Pap smear testing has reduced incidence in high-income countries, implementation has largely been unsuccessful in low-resource settings due to insufficient budgets, lack of healthcare delivery infrastructure and competing health priorities. Tailored protocols that maximize health benefits under operational constraints are needed. This study presents a framework for examining health and economic tradeoffs between screening test sensitivity, population coverage and follow-up of screen-positive women, to help decision-makers identify where program investments yield the greatest value. © 2015 UICC.


Campos N.G.,Center for Health Decision Science | Maza M.,Basic Health International | Alfaro K.,Basic Health International | Gage J.C.,U.S. National Cancer Institute | And 6 more authors.
International Journal of Cancer | Year: 2015

Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP. What's new? While most high-income countries have reduced cervical cancer incidence through widespread Pap smear testing, Pap-based screening programs in low-resource settings have faced challenges achieving adequate population coverage, quality, and management of abnormal Pap results. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project - a phased project implementing HPV DNA-based screening with the careHPV test - the authors assessed the cost-effectiveness of two algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. This is one of the earliest assessments of the cost-effectiveness of careHPV testing incorporating data from a real-world demonstration project. © 2015 UICC.


Wentzensen N.,U.S. National Institutes of Health | Fetterman B.,Kaiser Permanente | Tokugawa D.,Kaiser Permanente | Schiffman M.,U.S. National Institutes of Health | And 6 more authors.
Cancer Cytopathology | Year: 2014

BACKGROUND Dual-stain cytology for p16 and Ki-67 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual-stain cytology among 10 newly trained evaluators. METHODS In total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16/Ki-67 cytology. All participants underwent p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual-stain cytology was measured using the percentage agreement, individual and aggregate κ values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual-stain cytology. RESULTS The percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the κ values ranged from 0.65 to 0.81. The combined κ value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual-stain positivity increased with greater numbers of p16/Ki-67-positive cells on the slides. CONCLUSIONS Good to excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16/Ki-67 dual-stain evaluation can be implemented in routine cytology practice with limited training. © 2014 American Cancer Society.


Grant B.D.,Rice University | Smith C.A.,Rice University | Castle P.E.,Global Coalition Against Cervical Cancer | Castle P.E.,Yeshiva University | And 2 more authors.
Vaccine | Year: 2016

Objective To develop and evaluate a paper-based point-of-care HPV serology test to determine if an individual has received two or more HPV immunizations. Methods The paper-based immunoassay was constructed using a nitrocellulose lateral flow strip with adsorbed HPV16 virus-like particles serving as the capturing moiety. Three capture zones containing virus-like particles were placed in series to allow for visual discrimination between high and low HPV16 plasma antibody concentrations. A plasma separation membrane was used to allow whole blood to be applied directly to the assay. All reagents were dried on glass fiber pads during device fabrication and were rehydrated with buffer at the time of use. A pilot study consisting of 35 subjects with a history of zero, one, two or three HPV vaccines was conducted to evaluate the immunoassay. The completed paper-based immunoassays were scanned for visual interpretation by three researchers who were blinded to the true results and separately evaluated quantitatively using MATLAB. Results For the 28 tests valid for analysis, fifteen subjects reported receiving two or more HPV vaccines, three reported receiving one, and ten reported having no HPV vaccinations. The paper-based immunoassays for all fifteen subjects who reported having received two or more HPV vaccines were judged positive by all researchers. Twelve of the thirteen tests from individuals reporting one or zero vaccinations were deemed negative by all observers. One test from an unvaccinated individual was judged positive by two out of three reviewers. Quantitatively, all tests were correctly separated between the two groups. Conclusions We successfully designed and tested a HPV serology test amenable to the point-of-care. The device showed promising results in a pilot study for discriminating between those who received two or more HPV vaccinations and those who did not. Furthermore, this device offers a platform for producing other semi-quantitative point-of-care serological tests. © 2016 The Authors


Chen W.,Peking Union Medical College | Jeronimo J.,PATH | Zhao F.-H.,Peking Union Medical College | Qiao Y.-L.,Peking Union Medical College | And 11 more authors.
Journal of Clinical Virology | Year: 2014

Background: careHPV is a new, lower-cost DNA test for human papillomavirus (HPV). There are limited analytic comparisons of careHPV against a referent HPV DNA test like Hybrid Capture 2 (HC2). Objective: To assess the test agreement between careHPV and HC2 on self- and clinician-collected specimens. Study design: In a population of 7541 women living in rural China, women provided a self-collected (sc) and two clinician-collected (cc) specimens and underwent visual inspection after acetic acid (VIA). The sc specimen and one cc specimen were tested by careHPV and HC2; a random subset of specimens was tested for HPV genotypes. Results: The percent positive on cc specimens and sc specimens was 14.69% and 14.97% for careHPV, respectively, and 15.05% and 18.53% for HC2, respectively; HC2 testing of sc specimens was more likely to test positive than other combinations of tests and specimens (p<0.0001 for all comparisons). The agreement between different tests on the same specimens (kappa=0.787 and 0.691 for cc and sc specimens, respectively) was better than the same test on different specimens (kappa=0.653 and 0.649 for HC2 and careHPV, respectively). Disagreement between the same test on different specimens increased with increasing participant age (ptrend=0.0001 for HC2 and 0.002 for careHPV). HC2-positive/careHPV-negative specimens were more likely to test positive for non-carcinogenic HPV genotype than test HPV negative whereas the converse was true for HC2-negative/careHPV-positive specimens. Discussion: The agreement for HPV DNA detection between careHPV and HC2 was good to very good. © 2014 Elsevier B.V.


Stoler M.H.,University of Virginia | Stoler M.H.,University of New Mexico | Ronnett B.M.,Johns Hopkins Medical Institutions | Joste N.E.,University of New Mexico | And 16 more authors.
American Journal of Surgical Pathology | Year: 2015

Diagnostic interpretation of a cervical biopsy is a key element in the decision to treat or not to treat a woman with an abnormal screening test. This study assesses the variability of these diagnostic interpretations on a population basis using the New Mexico HPV Pap Registry database. An experienced panel of gynecologic pathologists reviewed a stratified random sample of 6272 biopsies, which was then extrapolated to the entire population of 21,297 biopsies read by the community pathologists. Diagnoses by the community and panel pathologists were compared, and paired diagnoses were correlated with positivity for human papillomavirus 16 (HPV16) and any high-risk HPV as objective measures of progressive potential. Panel agreement with the community diagnosis was 38.2% for cervical intraepithelial neoplasia grade 1 (CIN1), 38.0% for CIN grade 2 (CIN2), 68.0% for CIN grade 3 (CIN3), and 70.6% for cancer. The κ value was 0.46 overall but higher for dichotomous categorization based on CIN2 or CIN3 cutoff points (0.68 and 0.67, respectively). On a population basis, there were fewer CIN1 and more negative diagnoses in the panel review but similar proportions of CIN2 and CIN3. HPV16 and high-risk HPV positivity increased with disease severity, but panel review did not improve the correlation of higher-grade disease with these objective measures. In this population-based study of the variability in cervical diagnoses, we noted significant variability in the community and panel diagnoses, especially for CIN2, the threshold for excisional treatment. New biomarkers are needed to more accurately stratify precursor lesions according to their malignant potential. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


PubMed | PATH, University of Virginia, Global Coalition against Cervical Cancer and Peking Union Medical College
Type: Journal Article | Journal: International journal of cancer | Year: 2016

This study examined the efficacy of the OncoE6 Cervical Test, careHPV and visual inspection with acetic acid (VIA) in identifying women at risk for cervical cancer and their capability to detect incident cervical precancer and cancer at 1-year follow-up. In a population of 7,543 women living in rural China, women provided a self-collected and two clinician-collected specimens and underwent VIA. All screen positive women for any of the tests, a 10% random sample of test-negative women that underwent colposcopy at baseline, and an additional 10% random sample of test-negative women who did not undergo colposcopy at baseline (n = 3,290) were recruited. 2,904 women were rescreened 1 year later using the same tests, colposcopic referral criteria, and procedures. Sensitivities of baseline tests to detect 1-year cumulative cervical intraepithelial neoplasia Grade 3 or cancer (CIN3+) were 96.5% and 81.6% for careHPV on clinician-collected and self-collected specimens, respectively, and 54.4% for OncoE6 test. The OncoE6 test was very specific (99.1%) and had the greatest positive predictive value (PPV; 47.7%) for CIN3+. Baseline and 1-year follow-up cervical specimens testing HPV DNA positive was sensitive (88.0%) but poorly predictive (5.5-6.0%) of incident CIN2+, whereas testing repeat HPV16, 18 and 45 E6 positive identified only 24.0% of incident CIN2+ but had a predictive value of 33.3%. This study highlights the different utility of HPV DNA and E6 tests, the former as a screening and the latter as a diagnostic test, for detection of cervical precancer and cancer.


PubMed | PATH, University of Virginia, Global Coalition Against Cervical Cancer and Peking Union Medical College
Type: Comparative Study | Journal: Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology | Year: 2014

careHPV is a new, lower-cost DNA test for human papillomavirus (HPV). There are limited analytic comparisons of careHPV against a referent HPV DNA test like Hybrid Capture 2 (HC2).To assess the test agreement between careHPV and HC2 on self- and clinician-collected specimens.In a population of 7541 women living in rural China, women provided a self-collected (sc) and two clinician-collected (cc) specimens and underwent visual inspection after acetic acid (VIA). The sc specimen and one cc specimen were tested by careHPV and HC2; a random subset of specimens was tested for HPV genotypes.The percent positive on cc specimens and sc specimens was 14.69% and 14.97% for careHPV, respectively, and 15.05% and 18.53% for HC2, respectively; HC2 testing of sc specimens was more likely to test positive than other combinations of tests and specimens (p<0.0001 for all comparisons). The agreement between different tests on the same specimens (kappa=0.787 and 0.691 for cc and sc specimens, respectively) was better than the same test on different specimens (kappa=0.653 and 0.649 for HC2 and careHPV, respectively). Disagreement between the same test on different specimens increased with increasing participant age (ptrend=0.0001 for HC2 and 0.002 for careHPV). HC2-positive/careHPV-negative specimens were more likely to test positive for non-carcinogenic HPV genotype than test HPV negative whereas the converse was true for HC2-negative/careHPV-positive specimens.The agreement for HPV DNA detection between careHPV and HC2 was good to very good.


Schiffman M.,U.S. National Cancer Institute | Burk R.D.,Yeshiva University | Boyle S.,Hoffmann-La Roche | Raine-Bennett T.,Kaiser Permanente | And 10 more authors.
Journal of Clinical Microbiology | Year: 2015

The effective management of women with human papillomavirus (HPV)-positive, cytology-negative results is critical to the introduction of HPV testing into cervical screening. HPV typing has been recommended for colposcopy triage, but it is not clear which combinations of high-risk HPV types provide clinically useful information. This study included 18,810 women with Hybrid Capture 2 (HC2)-positive, cytology-negative results and who were age ≥30 years from Kaiser Permanente Northern California. The median follow-up was 475 days (interquartile range [IQR], 0 to 1,077 days; maximum, 2,217 days). The baseline specimens from 482 cases of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and 3,517 random HC2-positive noncases were genotyped using 2 PCR-based methods. Using the case-control sampling fractions, the 3-year cumulative risks of CIN3+ were calculated for each individual high-risk HPV type. The 3-year cumulative risk of CIN3+ among all women with HC2-positive, cytology-negative results was 4.6%. HPV16 status conferred the greatest type-specific risk stratification; women with HC2-positive/HPV16-positive results had a 10.6% risk of CIN3+, while women with HC-2 positive/HPV16-negative results had a much lower risk of 2.4%. The next most informative HPV types and their risks in HPV-positive women were HPV33 (5.9%) and HPV18 (5.9%). With regard to the etiologic fraction, 20 of 71 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma in the cohort were positive for HPV18. HPV16 genotyping provides risk stratification useful for guiding clinical management; the risk among HPV16-positive women clearly exceeds the U.S. consensus risk threshold for immediate colposcopy referral. HPV18 is of particular interest because of its association with difficult-to-detect glandular lesions. There is a less clear clinical value of distinguishing the other high-risk HPV types. Copyright © 2015, American Society for Microbiology. All Rights Reserved.


PubMed | Kaiser Permanente, Hoffmann-La Roche, U.S. National Cancer Institute, Information Management Services and 2 more.
Type: Journal Article | Journal: Journal of clinical microbiology | Year: 2014

The effective management of women with human papillomavirus (HPV)-positive, cytology-negative results is critical to the introduction of HPV testing into cervical screening. HPV typing has been recommended for colposcopy triage, but it is not clear which combinations of high-risk HPV types provide clinically useful information. This study included 18,810 women with Hybrid Capture 2 (HC2)-positive, cytology-negative results and who were age 30 years from Kaiser Permanente Northern California. The median follow-up was 475 days (interquartile range [IQR], 0 to 1,077 days; maximum, 2,217 days). The baseline specimens from 482 cases of cervical intraepithelial neoplasia grade 3 or cancer (CIN3+) and 3,517 random HC2-positive noncases were genotyped using 2 PCR-based methods. Using the case-control sampling fractions, the 3-year cumulative risks of CIN3+ were calculated for each individual high-risk HPV type. The 3-year cumulative risk of CIN3+ among all women with HC2-positive, cytology-negative results was 4.6%. HPV16 status conferred the greatest type-specific risk stratification; women with HC2-positive/HPV16-positive results had a 10.6% risk of CIN3+, while women with HC-2 positive/HPV16-negative results had a much lower risk of 2.4%. The next most informative HPV types and their risks in HPV-positive women were HPV33 (5.9%) and HPV18 (5.9%). With regard to the etiologic fraction, 20 of 71 cases of cervical adenocarcinoma in situ (AIS) and adenocarcinoma in the cohort were positive for HPV18. HPV16 genotyping provides risk stratification useful for guiding clinical management; the risk among HPV16-positive women clearly exceeds the U.S. consensus risk threshold for immediate colposcopy referral. HPV18 is of particular interest because of its association with difficult-to-detect glandular lesions. There is a less clear clinical value of distinguishing the other high-risk HPV types.

Loading Global Coalition Against Cervical Cancer collaborators
Loading Global Coalition Against Cervical Cancer collaborators