Dr. Cara Martin

Title

CERVIVA: Making Connections and Creating Impact

Summary

The goal of CERVIVA's education and outreach programme is to create awareness, inform and effectively engage the public, health care professionals and healthcare providers on public health issues related to HPV associated diseases and on the specific research programmes underway within CERVIVA, which are addressing some of these issues. Our goal is to motivate and engage the general public and health care providers to actively participate in the research, which will ultimately inform cancer prevention strategies in Ireland. We will achieve this goal by engaging in a series of education and outreach activities with key stakeholders, including the general public, CervicalCheck and The National Cancer Control Programme, and health care providers. Our education and outreach programme will provide innovative solutions including; running a National HPV Awareness Day; production of a CERVIVA infomercial which can be shown in clinic waiting rooms and on our website; developing a mobile website; hosting a series of public talks at town hall events around the country; and producing an annual CERVIVA newsletter. For more information on our research and education and outreach initiatives please see our website http://www.cerviva.ie.

Funding Agency

Health Research Board, Ireland

Date From

01/12/2016

Date To

31/01/2017

Title

Biomedical Diagnostics Institute 2 [BDI2] SFI CSET ONC1 Programme

Summary

Funding Agency

Science Foundation Ireland

Date From

2010

Date To

2015

Title

CERVIVA: Working towards a world class cervical screening system for Irish Women.

Summary

Project Goals: To develop new screening tools and diagnostics in cervical screening. Project Aims: 1.automation and its impact on cervical screening 2.health economic evaluation of automated cervical screening with the aim to provide a sound basis for decisions on developing a cost-effective cervical screening programme in the context of changing screening technologies 3.examine the attitudes of women to cervical screening and HPV testing 4.critically examine the impact of a positive smear and HPV test result in Irish women 5.examine streamlining cervical screening through the introduction of ancillary HPV testing: in specific management protocols 6.health economic evaluation of introducing HPV ancillary testing in the Irish population 7.the impact of HPV vaccines on cervical cancer and screening programmes 8.introduction of quality initiatives in a routine screening service through the development of a virtual slide EQA scheme 9.improvement of the existing opportunistic screening service in the Republic of Ireland 10.carry out blue-sky research in the area of cancer biochip development

Funding Agency

HRB

Date From

1st Sept 2006

Date To

31st August 2011

Title

CERVIVA: The HPV Educate Project

Summary

Funding Agency

Health Research Board, Ireland

Date From

01/12/2017

Date To

30/11/2018

Title

HPV mRNA and p16 INK4a detection for improved diagnosis and management of cervical neoplasia in smokers.

Summary

To evaluate a combined HPV mRNA and p16INK4a detection approach for detecting high grade cervical disease in women referred to colposcopy resulting in improved patient management and reduced costs to healthcare providers. Specific aims: 1. To define a consistent, accurate and adequate scoring mechanism for microscopic interpretation of p16INK4a immunohistochemistry and immunocytochemistry. 2. To correlate expression of p16INK4a expression with expression of HPV E6/E7 mRNA in cytological smear specimens and urinary cotinine levels in women attending colposcopy for management of low and high grade cervical lesions. 3. To correlate p16INK4a, HPV E6/E7 mRNA expression and urinary cotinine levels in cytological smear and urine specimens with histological specimens from the same patients. 4. To determine the PPV and specificity of p16INK4a and HPV mRNA detection at time of referral to colposcopy for predicting disease outcome.

Funding Agency

Cancer Research Ireland

Date From

1st Oct 2009

Date To

30th Sept 2012

Title

Development of novel therapeutics in ovarian cancer

Summary

Validation of functional role of novel genes and miRNAs in recurrent ovarian cancer specimens and development of novel therapeutics. This project is critically examining several miRNA molecules in recurrent ovarian cancer

Funding Agency

The Emer Casey Foundation

Date From

01/10/2008

Date To

30/09/2011

Title

Enhancing the Evidence Base for Cost-Effectiveness Analysis in Ireland: Building Improvements from the Intervention-Specific to System-Wide Levels

Summary

Funding Agency

Health Research Board, Ireland

Date From

01/07/2018

Date To

30/06/2022

Title

CERVIVA: From episodic care to disease prevention and management: Developing analytical skills and interdisciplinary learning from the case of HPV related cancers.

Summary

The CERVIVA ICE programme represents an integrated inter-disciplinary proposal that is transformative and capacity-enhancing for 3 Fellows working in 3 key areas of health services research: epidemiology, economics and health psychology/intervention development. The application builds on substantial existing capacity and expertise within the internationally recognised CERVIVA research consortium (www.cerviva.ie) and extends the coverage of its research effort by addressing a series of important knowledge gaps within cervical pre-cancer/cancer and Human papillomavirus (HPV)-associated head and neck cancer [HNSCC]; these knowledge gaps also represent important challenges for policy-makers, service providers and health professionals. Through an integrated interdisciplinary programme, the fellows will seek to derive significant outputs in three areas: Area 1 (Epidemiology): Advancing the understanding of the natural history of HPV infection in the oral cavity (prevalence, persistence, clearance); developing a mathematical-biological model of the natural history of HPV infection in head and neck cancer; and extended longitudinal analysis of biomarkers for triage in cervical pre-cancer. Area 2 (Health economics): Assessing the cost-effectiveness of novel biomarkers in cervical cancer prevention; and quantification of the differences in costs and effect of different strategies for the treatment of head and neck cancer, focusing on the potential gains from early detection. Area 3 (Health psychology/intervention development): Developing and testing theorybased interventions to: reduce adverse psychological after-effects in women undergoing colposcopy and related procedures; and support health professionals in discussing HPV with head and neck cancer patients. The programme places significant emphasis on advanced skills development, career training, academic placement and capacity enhancement. Ultimately it will develop individuals with the potential to become future leaders in health services research as well as improving health services and health in Ireland.

Funding Agency

Health Research Board

Date From

14/09/2015

Date To

13/01/2019

Title

What influences cervical screening uptake in older women and how can screening programmes translate this knowledge into behaviour changing strategies? A CERVIVA-CervicalCheck co-production project

Summary

and mortality. To achieve these benefits, high coverage is essential. In Ireland, the coverage target is 80%. While overall coverage has risen (from 61% to 79%) since the programme started in 2008, it has consistently been lower in older (50-60 years) than younger (25-49 years) women. This distinctive pattern is not seen in other countries with organised programmes and the reasons for it are unknown. Women in their early 50s are at risk of developing cervical cancer and screening at that age substantially reduces cancer risk for the subsequent 30 years. Thus, it is important to attain high screening coverage in older women. This CERVIVA-CervicalCheck co-production project will generate evidence on the influences on cervical screening participation among older women in Ireland, to inform development and implementation of evidence-based strategies to increase screening coverage in this group. A mixed-methods design will be used, underpinned by a theoretical framework of behaviour change. Phase 1 will involve in-depth interviews exploring influences on, barriers to, and enablers of, cervical screening participation; older and younger women and women with adequate and inadequate screening histories will be compared. Phase 2 will involve a postal survey of older women, comparing those with adequate and inadequate screening histories, to identify the most important influences on screening participation and inter-relationships between these. Phase 3 will triangulate phase 1 and 2 results and undertake a behavioural analysis to begin to generate evidence-based solutions for how screening participation may be changed. The findings will be translated by the National Screening Service into strategies to improve participation in older women, thereby optimising effectiveness of cervical screening in Ireland and delivering health gains for individual women and the population. The knowledge gained may also be applicable to other screening programmes in Ireland.

Funding Agency

Health Research Board, Ireland

Date From

03/10/2017

Date To

02/09/2019

Title

Systems biology approaches to cervical pre-cancer and cancer SYSTEMCERV

Summary

Funding Agency

European Union 7th Framework Programme.

Date From

1/11/2012

Date To

31/10/2014

Title

CERVIVA 2: building capacity and advancing research and patient care in cervical screening and other HPV associated diseases in Ireland.

Summary

Human Papillomavirus [HPV] is the primary aetiological agent in the pathogenesis of cervical cancer and pre-cancer. HPV is causally implicated in other cancers, including head and neck cancers. Prophylactic HPV vaccination is being introduced as a primary cervical cancer prevention strategy in many countries including Ireland. This presents new challenges for health service providers. The proposed programme will address several of these challenges through the highly successful and dynamic multidisciplinary CERVIVA consortium, supported by a national and international collaborator network. Workpackage 1 will evaluate strategies for triage of women with a HPV-positive primary screening test. Residual LBC samples from around 13,000 women undergoing routine screening will be screened for HPV and, in HPV-positive women, a molecular panel of tests will be evaluated: HPV16/18 genotyping, E6/E7mRNA, p16INK4a/ki67, and TOPO2A/MCM2 [ProExC]. Test performance for detection of CIN3 over 5-years will be evaluated. Workpackage 2 will determine the optimal cervical screening strategy in the HPV vaccination era. Mathematical models will be used to evaluate, epidemiologically and economically, [a] the impact on performance of current cervical screening protocols of entry of HPV-vaccinated women into screening; and [b] alternative screening strategies for a mixed population of vaccinated and un-vaccinated women. Workpackage 3 will evaluate the novel screening tool, RAMAN spectroscopy. A within-subject trial of 3000 women referred for colposcopy will be conducted, comparing spectroscopy and cytology for detection of CIN. Workpackage 4 involves a population-based study of the epidemiology of HPV infection in head and neck cancers. HPV prevalence/genotypes will be assessed in head and neck tumour specimens; specifically oropharyngeal, oral cavity and laryngeal cancer, identified via the National Cancer Registry. Treatment and outcomes will be compared between HPV-positive and negative cases. This programme will inform cancer prevention policy and practice in Ireland and internationally and, ultimately, improve health outcomes.

Funding Agency

Health Research Board

Date From

1/04/2013

Date To

30/03/2019

Title

CERVIVA 2: building capacity and advancing research and patient care in cervical screening in Ireland.

Summary

Funding Agency

Health Research Board, Ireland

Date From

01/09/2011

Date To

31/08/2014

Title

Platform for Advanced Single Cell-Manipulation and Analysis

Summary

Project Goals: To develop PASCA a Platform for Advance Single Cell-Manipulation and Analysis (PASCA), which is a novel approach to perform cell research or cell based experiments with single cells instead of ensembles (batches) of cells. Project Aims: Firstly to establish and validate the PASCA platform using the SCM instrument as the key enabling technology. Secondly, scientific results will be obtained in the framework of the life science applications realized by the PASCA platform. The application, for the first time will allow multi-dimensional characterisation of isolated pre-cancer and cancer cells from complex cell populations.

Funding Agency

European Union FP7 Programme

Date From

1st Sept 2010

Date To

31st August 2013

Title

Automatic Detection of Disease Related Molecular Cell Activity

Summary

EU 6th Framework Programme STREP (Specific Targeted Research or Innovation Projects). 2005-2008. (Co-Applicant) (FP6 2004-ISTNMP2)

Funding Agency

EU 6th Framework

Date From

2005

Date To

2008

Title

A novel tool for cervical cancer screening based on low resolution Raman spectroscopy, CERVASSIST.

Summary

To develop a robust commercial product for rapid and low cost cervical cancer screening based on a commercially available micro Raman system. Project Aims: 1.To conduct a large scale study on low resolution Raman spectroscopy for discriminating between normal and abnormal cervical tissue and smear samples. 2.To use multivariate techniques to develop an algorithm to classify normal, CIN I, CIN II, CIN III and invasive carcinoma samples for the non specialist user 3.To customise a commercially available micro Raman system to make it suitable for cervical cancer screening 4.To conduct beta testing at the National Maternity Hospital and the Coombe Women and Infants University Hospital to test and validate the technology

Funding Agency

Enterprise Ireland

Date From

June 2009

Date To

may 2012

Title

'Molecular Pap test' for cervical cancer screening - detecting HPV infection and cellular abnormalities in exfoliated cervical cells

Summary

Funding Agency

Enterprise Ireland

Date From

2011

Date To

2014

Title

Non-coding miRNAs as regulators of chemoresistance in ovarian cancer,

Summary

Funding Agency

Royal City of Dublin Hospital Trust Fund

Date From

2011

Date To

2014

Title

Specific Targeting of Cancer Stemness: Potential Cancer Therapy?

Summary

This grant is examining the effect of knocking-down of 5 target miRNAs in embryonal carcinoma cell lines.

Funding Agency

Cancer Research Ireland

Date From

1st Oct 2008

Date To

30th Sept 2011

Title

Regulation and Function of Toll-like Receptors in Ovarian Cancer: A Synergistic Model

Summary

Characterisation of TLR4/MyD88 in ovarian cancer

Funding Agency

Cancer Research Ireland

Date From

1st Oct 2008

Date To

31st March, 2011

Title

CERVIVA-Vax: Monitoring the impact of HPV vaccination in Ireland

Summary

Funding Agency

Health Research Board, Ireland

Date From

01/02/2018

Date To

31/01/2022

Title

CERVIVA studentship for ECHO study

Summary

Head and neck cancer (HNC) is a collective term for a range of cancers arising in the mucosal lining at various sites in the head and neck, including the oral cavity, oropharynx and larynx. It is the sixth most common cancer in the world, with more than 630,000 new cases diagnosed each year and 350,000 deaths. In Ireland, more than 400 new cases of HNC present annually. HNC was traditionally considered to be a disease of the elderly and of men, with many cases believed to be due to cumulative exposure to tobacco and alcohol. However, in North America and Europe incidence rates have been increasing over the past few decades, especially in younger people and in women- populations less likely to have strong histories of tobacco or alcohol exposure. The rising incidence has tended to be limited to particular sites, most notably squamous cell carcinoma of the oropharynx, tonsil and tongue. These trends have pointed to the emergence of a new risk factor- HPV. HPV DNA has been found to be present in a significant proportion of HNCs. In a major meta-analysis published in 2005, 36% of cancers of the oropharynx (including the tonsil) were HPV positive (Kreimer 2005) and, in a more recent meta-analysis, HPV16 accounted for 96% of HPV-positive squamous cell carcinomas of the oropharynx (Mehanna 2012). In a major meta-analysis published in 2014, 45.8% of cancers of the oropharynx (including the tonsil) were HPV positive (Ndiaye et al). The International Agency for Research on Cancer (IARC) has concluded that there is strong epidemiological evidence for a casual role for HPV16 in the aetiology of cancers in the oropharynx and tonsil. Evidence around cancers of the oral cavity and larynx are more controversial. In the 2005 meta-analysis 24% of these cancers were HPV positive. However results of case-control studies have been inconsistent and the range in prevalence in individual studies is wide. Results of various studies based on inferred HPV status, and some clinical trials of oropharyngeal squamous cell cancers, suggest that patients with HPV-positive cancers have a better prognosis than HPV-negative cancers. If confirmed at the population level, these observations raise the possibility that HPV-related cancers may be treated less aggressively (Arbyn 2011). There are significant uncertainties in the evidence-base around HPV in HNC. Studies have been conducted in a limited number of populations and many have been small and included selected samples. Prevalence of HPV positivity at specific sites and sub-sites is uncertain, especially over time. While HPV16 has been reasonably well investigated, the prevalence of other HPV types is less clearly established. Moreover, the impact of HPV status on survival at various sites in the head and neck requires further exploration. This study will generate the first data on HPV prevalence and genotype distribution, and associations between HPV status and outcome, in head and neck cancers in Ireland. Given the potential impact HPV vaccination may have on these cancers this is an essential piece of research.

Funding Agency

The Coombe Women and Infants University Hospital

Date From

01/04/2016

Date To

31/03/2019

Title

Antibody profiling in ovarian cancer

Summary

Identification of novel auto-antibodies in the serum of ovarian cancer patients using a novel human protein expression array library. Grant 3

Funding Agency

Emer Casey Foundation

Date From

01/04/2009

Date To

31/03/2012

Title

: EU 7th FP grant (FP7-HEALTH-2007-A) Automatic Cancer Screening Based on real-time PCR

Summary

Project Goals: To develop and to validate a point of care (POC) diagnostic system for cancer screening, combining the methods of real time PCR and DNA microarrays. Project Aims: To develop a combined thermal cycler and optical detection system to perform PCR cycling and microarray detection simultaneously To develop a microfluidic cartridge containing light guiding components to enable attenuated total reflection (ATR) and the immobilized microarray within a reaction chamber, which is amenable for PCR cycling and optical readout by TIRF .To develop a novel type of assay protocol (the mediator probe assay) to enable screening of any nucleic acid by a single universal/ generic microarray To test a new combinational approach for cervical cancer screening including both HPV and human gene biomarker testing . To perform a clinical feasibility and validation study to benchmark the performance of the new test to existing diagnostic platforms with respect to HPV diagnostics

Funding Agency

European Union FP7 Programme

Date From

1st August 2008

Date To

31st July, 2011

Title

Hsa-miR-141 and hsa-miR-223 are central to Ovarian Serous Carcinoma Pathogenesis through Regulation of JAG1 and SMARCD1 proteins.

Summary

Project Goals: To assess the the role of two miRNAs in ovarian serous carcinomas and evaluation of the effects of knocking down these targets using anti-mIRs.

Funding Agency

Cancer Research Ireland

Date From

1st April 2009

Date To

31st March, 2012