Building capacity for integrated knowledge translation: a description of what we can learn from trainees' experiences during the COVID-19 pandemic.

The use of collaborative health research approaches, such as integrated knowledge translation (IKT), was challenged during the COVID-19 pandemic due to physical distancing measures and transition to virtual platforms. As IKT trainees (i.e. graduate students, postdoctoral scholars) within the Integrated Knowledge Translation Research Network (IKTRN), we experienced several changes and adaptations to our daily routine, work and research environments due to the rapid transition to virtual platforms. While there was an increased capacity to communicate at local, national and international levels, gaps in equitable access to training and partnership opportunities at universities and organizations have emerged. This essay explores the experiences and reflections of 16 IKTRN trainees during the first 2 years of the COVID-19 pandemic at the micro (individual), meso (organizational) and macro (system) levels. The micro level, or individual experiences, focuses on topics of self-care (taking care of oneself for physical and mental well-being), maintaining research activities and productivity, and leisure (social engagement and taking time for oneself), while conducting IKT research during the pandemic. At the meso level, the role of programmes and organizations explores whether and how institutions were able to adapt and continue research and/or partnerships during the pandemic. At the macro level, we discuss implications for policies to support IKT trainees and research, during and beyond emergency situations. Themes were identified that intersected across all levels, which included (i) equitable access to training and partnerships; (ii) capacity for reflexivity; (iii) embracing changing opportunities; and (iv) strengthening collaborative relationships. These intersecting themes represent ways of encouraging sustainable and equitable improvements towards establishing and maintaining collaborative health research approaches. This essay is a summary of our collective experiences and aims to provide suggestions on how organizations and universities can support future trainees conducting collaborative research. Thus, we hope to inform more equitable and sustainable collaborative health research approaches and training in the post-pandemic era.

A conceptual framework to describe and evaluate a socially accountable learning health system: Development and application in a northern, rural, and remote setting.

Health care and academic institutions are increasingly committing to social accountability, a strategic shift that requires priorities, activities, and evaluations to be co-determined with all relevant partners. Consequently, governments, accreditors, funders, and communities are calling for these institutions to communicate their progress towards social accountability. The purpose of this study was to develop a conceptual framework around a socially accountable learning health system. This article presents an integrated analysis of two studies: (i) a narrative review of 11 prominent social accountability and health services conceptual frameworks and (ii) a reflexive thematic analysis of 18 key informant interviews. Using a systematic conceptual framework development and integrated theory of change/realist evaluation methodologies, we describe a synthesis of these findings to develop a conceptual framework for describing and evaluating socially accountable health professional education. The resulting framework describes assessment phases of social accountability, transitions between phases, learning cycles, and the actors and systems that collectively mobilise social accountability at multiple levels in health and education systems. The framework can be used to evaluate interventions or characterise progress towards social accountability in different settings, as illustrated in the example at the end of the paper. The framework emphasises the significance of designing, mobilising, and evaluating social accountability as part of a contextualised learning health system.

Strategies for Increasing Cervical Cancer Screening Amongst First Nations Communities in Northwest Ontario, Canada.

The high burden of cervical cancer in Indigenous populations worldwide is due to underscreening and inadequate follow-up. Using qualitative, participatory action research, we interviewed health care staff to identify ways to increase screening recruitment in First Nations communities in Northwest Ontario, Canada. Our findings suggest the value of a multilevel social-ecological model to promote behavioral changes at the community, health care service and stakeholder, and decision-maker level. Participants emphasized the central role of First Nations women as nurturers of life and for the well-being of their family members. They stressed the importance of building awareness and motivation for cervical cancer screening through various activities including continuous education, hosting screening events specifically for women, improving the attitude and service of health care providers, and promoting screening tools and policies that complement and are respectful of First Nations women.

Teaching tools to engage Anishinaabek First Nations women in cervical cancer screening: Report of an educational workshop.

OBJECTIVE: To explore educational strategies for engaging First Nations women in Canada to attend cervical cancer screening. DESIGN: Within a participatory action research framework, semi-structured interviews with health-care providers in First Nations communities revealed that education about the value of screening is perceived as being a key factor to promote cervical cancer screening. SETTING: To obtain feedback from workshop informants, a 1-day educational workshop was held to identify appropriate educational intervention strategies, which would be applied in a forthcoming randomised controlled cervical screening trial. METHODS: Common discussion and discussion groups, which were facilitated by a First Nations workshop moderator and a note taker. RESULTS: This workshop helped to strengthen the ethical space dialogue with the First Nations communities with whom the study team had established research partnerships. The workshop atmosphere was relaxed and the invited informants decided that an educational health promotion event for community women needed to be held prior to inviting them to the cervical screening trial. Such an event would provide an opportunity to communicate the importance of attending regular cervical screening allowing women to make informed decisions about screening participation. Complementary promotional items, including an eye-catching pamphlet and storytelling, were also suggested. CONCLUSION: The key messages from the events and promotional items can help to destigmatise women who develop a type of cancer that is caused by a sexually transmitted virus that affects both men and women. Developing and implementing positive health education that respectfully depicts female bodies, sexuality and health behaviours through a First Nations lens is strongly warranted.

Engaging Canadian First Nations Women in Cervical Screening through Education.

Recognition of the need to decrease cervical cancer rates in Indigenous populations has been ongoing-yet few successful interventions have been reported. In addition, literature addressing the challenges and barriers associated with designing screening programs aimed to specifically reach Indigenous women is limited. Here, we report findings from a mixed methods cervical cancer research project conducted in partnership with 10 First Nations communities in northwest Ontario, Canada. Individual interviews with community health professionals (the majority of whom identified as First Nations) stressed that awareness of cervical screening benefits is lacking. In contrast, focus group participants (women with no formal health education) emphasized the desire to learn more about the science of human papillomavirus (HPV), and that a positive HPV or abnormal Papanicolaou test need not mean a woman will undoubtedly develop cervical cancer. Both the health professionals and the focus group participants highlighted that sexual health education must start early, in schools, preferably before girls are sexually active and that it has to continue throughout life to create a screening culture with a focus on women's wellbeing. Both interview and focus group participants highlighted that sexual health education must start early, in schools, preferably before girls are sexually active and that it has to continue throughout life to create a screening culture with a focus on women's wellbeing. Health professionals elaborated mainly on special events for community women whereas focus group participants also recognized the need to include community men in health education particularly for de-stigmatizing the sexually-transmitted HPV infection.

Changes in Children and Youth's Mental Health Presentations during COVID-19: A Study of Primary Care Practices in Northern Ontario, Canada.

Recent research suggests that children and youth are at increased risk of anxiety and depression due to the indirect effects of the COVID-19 pandemic. In Canada, children and youths may face additional hurdles in accessing mental health services in rural areas due to socioeconomic disadvantages and healthcare provider shortages worsened by the pandemic. Our study aimed to assess changes in primary healthcare utilization related to depression and anxiety among children and youth aged 10-25 years in Northern Ontario, Canada. We analyzed de-identified electronic medical record data to assess primary healthcare visits and prescriptions for depression and anxiety among children and youth aged 10-25 years. We used provider billing data and reasons for visits and antidepressant/antianxiety prescriptions compared with 21 months pre-pandemic (1 June 2018 to 28 February 2020) and 21 months during the pandemic (1 April 2020 to 31 December 2021). Our interrupted time series analysis showed an average increase in visits by 2.52 per 10,000 person-months and in prescriptions by 6.69 per 10,000 person-months across all ages and sexes. Females aged 10 to 14 years were found to have the greatest relative change in visits across all age-sex groups. The greatest relative increases in antianxiety and antidepression prescriptions occurred among females and males aged 10 to 14 years, respectively. These findings indicate that there were increased anxiety and depression presentations in primary healthcare among children and youths living in northern and rural settings during the COVID-19 pandemic. The increased primary healthcare presentations of anxiety and depression by children and youths suggest that additional mental health resources should be allocated to northern rural primary healthcare to support the increased demand. Adequate mental health professionals, accessible services, and clinical recommendations tailored to northern rural populations and care settings are crucial.

Comparing and using prominent social accountability frameworks in medical education: moving from theory to implementation in Northern Ontario, Canada.

Background: Social accountability in medical education is conceptualized as a responsibility to respond to the needs of local populations and demonstrate impact of these activities. The objective of this study was to rigorously examine and compare social accountability theories, models, and frameworks to identify a theory-informed structure to understand and evaluate the impacts of medical education in Northern Ontario. Methods: Using a narrative review methodology, prominent social accountability theories, models, and frameworks were identified. The research team extracted important constructs and relationships from the selected frameworks. The Theory Comparison and Selection Tool was used to compare the frameworks for fit and relevance. Results: Eleven theories, models, and frameworks were identified for in-depth analysis and comparison. Two realist frameworks that considered community relationships in medical education and social accountability in health services received the highest scores. Frameworks focused on learning health systems, evaluating institutional social accountability, and implementing evidence-based practices also scored highly. Conclusion: We used a systematic theory selection process to describe and compare social accountability constructs and frameworks to inform the development of a social accountability impact framework for the Northern Ontario School of Medicine. The research team examined important constructs, relationships, and outcomes, to select a framework that fits the aims of a specific project. Additional engagement will help determine how to combine, adapt, and implement framework components to use in a Northern Ontario framework.

Contexte: La responsabilité sociale dans l'éducation médicale est conceptualisée comme étant la responsabilité de répondre aux besoins des populations locales et de démontrer l'impact de ces activités. L'objectif de cette étude était d'examiner rigoureusement et de comparer les théories, les modèles et les cadres de la responsabilité sociale afin d'élaborer un dispositif ayant des fondements théoriques qui servirait à cerner et à évaluer les retombées de l'éducation médicale dans le Nord de l'Ontario. Méthodes: Suivant une méthodologie de revue narrative, les théories, modèles et cadres principaux de la responsabilité sociale ont été recensés. L'équipe de recherche a extrait les concepts et les relations importants des cadres sélectionnés. Les cadres ont ensuite été comparés sur le plan de l'adéquation et de la pertinence à l'aide d'un outil de comparaison et de sélection des théories (le Theory Comparison and Selection Tool). Résultats: Onze théories, modèles et cadres ont été retenus pour une analyse et une comparaison approfondies. Deux cadres réalistes prenant en considération les relations communautaires dans l'éducation médicale et la responsabilité sociale dans les services de soins de santé ont reçu les scores les plus élevés. Les cadres axés sur l'apprentissage des systèmes de santé e, sur l'évaluation de la responsabilité sociale des institutions et sur la mise en œuvre de pratiques fondées sur les données probantes ont également obtenu des scores élevés. Conclusion: Nous avons utilisé un processus systématique de sélection des théories pour décrire et comparer les construits et les cadres de responsabilité sociale afin d'éclairer le développement d'un cadre de référence sur les retombées de la responsabilité sociale pour l'École de médecine du Nord de l'Ontario. L'équipe de recherche a examiné les construits importants, les liens entre ces derniers et les retombées afin de choisir un cadre pouvant répondre aux objectifs d'un projet spécifique. Des travaux ultérieurs permettront de déterminer de quelle manière il sera possible de combiner, d'adapter et de mettre en œuvre les composantes de ce cadre qui sera utilisé dans le Nord de l'Ontario.

Integrating socially accountable health professional education and learning health systems to transform community health and health systems.

A learning health system aims to create value in health systems using data-driven innovations, quality improvement techniques, and collaborations between health system partners. Although the concept is mobilized through cycles of learning, most instantiations of the learning health system overlook the importance of formalized learning in educational settings. Social accountability in health professional education focuses on measurably improving people's health and health care, specifically through education and training activities. In this commentary, we argue that the idea of social accountability clearly articulates a rationale and a broad range of aspirations, whereas the learning health system offers an approach to achieve these goals. With a similar aim to a learning health system, social accountability promotes partnerships between health professional education, the health system, and communities in a way that allows for co-designed and contextualized interventions. On the other hand, learning health systems prioritize data, research, and analytic capacities to facilitate quality improvement. An integrative framework could enhance learning cycles by collectively designing interventions and innovations with people and communities from health, research, and education systems. As well as aspiring to improve population health and health equity, such a framework will consider broader impacts, including the degree of participation amongst a range of partners and the level of responsiveness to partners' priorities.

Development and field testing of a tool to elicit women's preferences among cervical cancer screening modalities.

OBJECTIVE: The objective of the present study is to describe the development and field testing of a preference-elicitation tool for cervical cancer screening, meeting International Patient Decision Aids Standards (IPDAS) quality criteria. METHODS: We developed a tool designed to elicit women's preferences among cervical cancer screening modalities. The Ottawa Decision Support Framework and IPDAS systematic development process guided the design, and we followed IPDAS criteria for conducting a field test in a real-world setting. Using social media recruitment strategies, we identified a convenience sample of Ontario women who were currently eligible for cervical screening to test the tool. We evaluated the feasibility, acceptability, balance of information, and ability to elicit women's informed, values-based preferences using an online survey embedded in the tool. RESULTS: Twenty-five women participated in the field test. Participants were aged 20 to 63 years , and identified as predominantly white (88%), living in Northern Ontario (68%), and most had university education (75%). Most participants (72%) considered the length of the website as "just right," and 100% indicated that they would find the tool useful for decision-making. Over two-thirds (68%) of participants perceived the information in the tool as "balanced." Almost all (92%) participants scored at least 4 out of 7 on the knowledge quiz, and most participants (84%) selected their preference in an informed, values-based way. CONCLUSION: The results from our field test of this tool provide preliminary evidence of the tool's feasibility, acceptability, balance, and ability to elicit women's informed, values-based preferences among available cervical screening modalities. Further research should elicit the distribution of preferences of cervical screening modalities in other regions, using a sample who represents the screening population and a rigorous study design. It will be important for researchers and screening programmes to evaluate the tool's ability to elicit women's informed, values-based preferences compared with educational materials.

"They Should Be Asking Us": A Qualitative Decisional Needs Assessment for Women Considering Cervical Cancer Screening.

In this study, we examine from multiple perspectives, women's shared decision-making needs when considering cervical screening options: Pap testing, in-clinic human papillomavirus (HPV) testing, self-collected HPV testing, or no screening. The Ottawa Decision Support Framework guided the development of the interview schedule. We conducted semi-structured interviews with seven screen-eligible women and five health care professionals (three health care providers and two health system managers). Women did not perceive that cervical screening involves a "decision," which limited their knowledge of options, risks, and benefits. Women and health professionals emphasized how a trusted primary care provider can support women making a choice among cervical screening modalities. Having all cervical screening options recommended and funded was perceived as an important step to facilitate shared decision making. Supporting women in making preference-based decisions in cervical cancer screening may increase screening among those who do not undergo screening regularly and decrease uptake in women who are over-screened.

Quality of reporting of patient decision aids in recent randomized controlled trials: A descriptive synthesis and comparative analysis.

OBJECTIVE: Variable reporting of patient decision aids (PDAs) in published articles raises uncertainty about whether the intervention meets the definition of a PDA. We appraised the quality of reporting of PDA characteristics in randomized controlled trials (RCTs). METHODS: RCTs eligible for the Cochrane review of PDAs and published June 2012 to April 2015 were included. Quality of PDA reporting was appraised using the International Patient Decision Aid Standards Instrument (v4.0). We descriptively synthesized and comparatively analysed qualifying and certification criteria reported in each publication against their presence in actual PDAs. RESULTS: Seventeen RCTs evaluating sixteen PDAs were included. Ten PDAs (58.8%) were reported using all qualifying criteria. Two (11.8%) were reported using all certification criteria. The median score for reporting qualifying criteria was 6 of 6 (range 4-6). The median score for reporting certification criteria was 2 of 10 (range 2-3) for screening and 1 of 6 (range 0-6) for treatment decisions. CONCLUSION: Reporting of PDAs in RCTs is suboptimal. Incomplete reporting poses challenges for clinicians and researchers needing to identify PDA content for clinical practice and/or future research. PRACTICE IMPLICATIONS: Authors should report IPDASi (v4.0) criteria in published articles. Reporting guidelines for PDA evaluation studies are in development to improve reporting within the scientific literature.

Colonial legacy and the experience of First Nations women in cervical cancer screening: a Canadian multi-community study.

Regular Papanicolaou (Pap) screening has dramatically reduced cervical cancer incidence in Canada since the 1950s. However, Indigenous women's rates of cervical cancer remain disproportionately high, a factor which is not acknowledged in national media or in educational materials reporting Canada's new cervical cancer screening guidelines. Here, we present findings from a cervical cancer screening initiative in Northwestern Ontario. Based on participatory action research, we worked with 10 First Nations communities in the Robinson Superior Treaty area to increase awareness of cervical cancer risk, develop culturally sensitive tools for screening and education and test the efficacy of human papillomavirus (HPV) self-sampling as an alternative to Pap cytology. We conducted 16 interviews with health care professionals and 9 focus groups with 69 women from the communities. A central theme for both health care providers (HCPs) and community members was the colonial legacy and its influence on women's experiences of cervical cancer screening. This was evidenced by a strong sense of body shyness, including shame related to sexuality and sexually transmitted infections, concerns about confidentiality in clinical encounters and distrust or caution around HCPs. Reaffirming women's traditional caregiving and educational roles, enhancing mother and daughter communication, improving cultural sensitivity in health care and education and adoption of HPV self-sampling to increase women's privacy and control of the cervical cancer screening experience were endorsed. We argue that education and screening initiatives must reflect the cultural preferences of Indigenous women, empowering them to take control of their experiences of health and body in cervical cancer screening.

Community-randomised controlled trial embedded in the Anishinaabek Cervical Cancer Screening Study: human papillomavirus self-sampling versus Papanicolaou cytology.

OBJECTIVES: The incidence of cervical cancer is up to 20-fold higher among First Nations women in Canada than the general population, probably due to lower participation in screening. Offering human papillomavirus (HPV) self-sampling in place of Papanicolaou (Pap) testing may eventually increase screening participation and reduce cervical cancer rates in this population. DESIGN: A community-randomised controlled screening trial. SETTING: First Nations communities in Northwest Ontario, Canada. PARTICIPANTS: Women aged between 25 and 69, living in Robinson Superior Treaty First Nations. The community was the unit of randomisation. INTERVENTIONS: Women were asked to complete a questionnaire and have screening by HPV self-sampling (arm A) or Pap testing (arm B). PRIMARY OUTCOME MEASURES: The number of women who participated in cervical screening. RANDOMISATION: Community clusters were randomised to include approximately equivalent numbers of women in each arm. RESULTS: 6 communities were randomised to arm A and 5 to arm B. One community withdrew, leaving 5 communities in each group (834 eligible women). Participation was <25%. Using clustered intention-to-treat (ITT) analysis, initial and cumulative averaged uptakes in arm A were 1.4-fold (20% vs 14.3%, p=0.628) and 1.3-fold (20.6% vs 16%, p=0.694) higher compared to arm B, respectively. Corresponding per protocol (PP) analysis indicates 2.2-fold (22.9% vs 10.6%, p=0.305) and 1.6-fold (22.9% vs 14.1%, p=0.448) higher uptakes in arm A compared to arm B. Screening uptake varied between communities (range 0-62.1%). Among women who completed a questionnaire (18.3% in arm A, 21.7% in arm B), the screening uptake was 1.8-fold (ITT; p=0.1132) or 3-fold (PP; p<0.01) higher in arm A versus arm B. CONCLUSIONS: Pap and HPV self-sampling were compared in a marginalised, Canadian population. Results indicated a preference for self-sampling. More research on how to reach underscreened Indigenous women is necessary. TRIAL REGISTRATION NUMBER: ISRCTN84617261.

Eliciting women's cervical screening preferences: a mixed methods systematic review protocol.

BACKGROUND: With the accumulation of evidence regarding potential harms of cancer screening in recent years, researchers, policy-makers, and the public are becoming more critical of population-based cancer screening. Consequently, a high-quality cancer screening program should consider individuals' values and preferences when determining recommendations. In cervical cancer screening, offering women autonomy is considered a "person-centered" approach to health care services; however, it may impact the effectiveness of the program should women choose to not participate. As part of a larger project to investigate women's cervical screening preferences and correlates of these preferences, this systematic review will capture quantitative and qualitative investigations of women's cervical screening preferences and the methods used to elicit them. DESIGN AND METHODS: This mixed methods synthesis will use a thematic analysis approach to synthesize qualitative, quantitative, and mixed methods evidence. This protocol describes the methods that will be used in this investigation. A search strategy has been developed with a health librarian and peer reviewed using PRESS. Based on this strategy, five databases and the gray literature will be searched for studies that meet the inclusion criteria. The quality of the included individual studies will be examined using the Mixed Methods Appraisal Tool. Three reviewers will extract data from the primary studies on the tools or instruments used to elicit women's preferences regarding cervical cancer screening, theoretical frameworks used, outcomes measured, the outstanding themes from quantitative and qualitative evidence, and the identified preferences for cervical cancer screening. We will describe the relationships between study results and the study population, "intervention" (e.g., tool or instrument), and context. We will follow the PRISMA reporting guideline. We will compare findings across studies and between study methods (e.g., qualitative versus quantitative study designs). The strength of the synthesized findings will be assessed using the validated GRADE and CERQual tool. DISCUSSION: This review will inform the development of a tool to elicit women's cervical screening preferences. Understanding the methods used to elicit women's preferences and what is known about women's cervical screening preferences will be useful for guideline developers who wish to incorporate a woman-centered approach specifically for cervical screening guidelines. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035737.

Using community engagement to inform and implement a community-randomized controlled trial in the anishinaabek cervical cancer screening study.

Social, political, and economic factors are directly and indirectly associated with the quality and distribution of health resources across Canada. First Nations (FN) women in particular, endure a disproportionate burden of ill health in contrast to the mainstream population. The complex relationship of health, social, and historical determinants are inherent to increased cervical cancer in FN women. This can be traced back to the colonial oppression suffered by Canadian FN and the social inequalities they have since faced. Screening - the Papinacolaou (Pap) test - and early immunization have rendered cervical cancer almost entirely preventable but despite these options, FN women endure notably higher rates of diagnosis and mortality due to cervical cancer. The Anishinaabek Cervical Cancer Screening Study (ACCSS) is a participatory action research project investigating the factors underlying the cervical cancer burden in FN women. ACCSS is a collaboration with 11 FN communities in Northwest Ontario, Canada, and a multidisciplinary research team from across Canada with expertise in cancer biology, epidemiology, medical anthropology, public health, virology, women's health, and pathology. Interviews with healthcare providers and community members revealed that prior to any formal data collection education must be offered. Consequently, an educational component was integrated into the existing quantitative design of the study: a two-armed, community-randomized trial that compares the uptake of two different cervical screening modalities. In ACCSS, the Research Team integrates community engagement and the flexible nature of participatory research with the scientific rigor of a randomized controlled trial. ACCSS findings will inform culturally appropriate screening strategies, aiming to reduce the disproportionate burden of cervical disease in concert with priorities of the partner FN communities.

Abundant expression of interleukin-21 receptor in follicular lymphoma cells is associated with more aggressive disease.

Recombinant interleukin-21 (IL-21) has potential utility in cancer therapy. Stimulation with IL-21 can induce apoptosis in follicular lymphoma (FL) cells, and existing studies have suggested that IL-21 signaling may function in tumor suppression. In order to elucidate the relationship between IL-21 receptor (IL-21R) expression and clinical and pathological features in FL, IL-21R was quantified in 114 pretreatment biopsy samples using either conventional immunohistochemistry or immunofluorescence microscopy and automated quantitative analysis (AQUA). Reduced expression of IL-21R was associated with favorable overall survival (p = 0.048). AQUA analysis showed an association with the presence of diffuse large B-cell lymphoma (DLBCL) in the biopsy sample (p = 0.03), and expression of IL-21R was up-regulated upon transformation of FL to DLBCL in two cases. Our results based on the largest survey to date raise the possibility that IL-21 signaling in FL cells, rather than being tumor suppressive, supports tumor progression and that therapeutic benefit could be realized by blocking IL-21R instead of stimulating it.

Differential expression of cell-cycle regulatory proteins defines distinct classes of follicular lymphoma.

Follicular lymphoma, a relatively common neoplasm of mature B lymphocytes, generally pursues an indolent clinical course. The disease is biologically heterogeneous, however, and aggressive instances associated with short survival are relatively common. Because defects in the regulation of apoptotic cell death are fundamental in follicular lymphoma pathogenesis, we hypothesized that deregulated expression of components of the Rb signaling pathway may promote cell proliferation, thereby complementing antecedent antiapoptotic mutations and producing more aggressive disease. We determined the differential expression of key cell-cycle regulatory proteins in lymphoma cells by incorporating formalin-fixed, paraffin-embedded samples from the initial, diagnostic biopsies from 127 cases of follicular lymphoma into tissue microarrays, histologic sections of which were stained by immunohistochemistry for p53, pRb, p16(INK4a), and cyclin D3. The results were ascertained by visual inspection and then correlated with histopathological and clinical parameters, including overall survival. Our findings show that increased abundance of p53 or p16(INK4a) is associated with reduced overall survival and conventional pathological markers of tumor aggressiveness including high histologic grade. Therefore, subjective quantification of cell-cycle regulatory proteins by immunohistochemistry can identify biologically and clinically distinct subsets of follicular lymphoma cases.