research proposal cancer

Cancer research writing: how to plan and write a research proposal

Do’s and Don’ts in writing a scientific literature review for health care research

What are the reporting guidelines to be followed while writing a biomedical literature review for a manuscript?

• There are several approaches to treat cancer cells like immune therapy, gene therapy which resists the patients from cancer cells.
• Writing a cancer research paper is not a simple task; it’s more difficult while collecting research paper.Pubrica gives full support in writing research article in various disciplines like cancer, drug resistance, cancer cells, etc., Pubrica can also support in experimental researches too.

Introduction:

Cancer is a universal leading cause of death world wide; there are several types of cancers; mainly, they are brain cancer, breast cancer, lungs cancer, kidney cancer etc. If research thesis should be published in a specific journal , then the documents should contain specific elements like abstracts, the body of the text, methods, results, discussion and conclusion. The steps which include in the hypothesis are

• The main target should be researches, and the searching content should highly related to the topic.
• The quality and integrity of the research paper should be high.
• The reference list should befrom books, chapters, articles which are related to the topics.

Challenges in cancer research writing:

Essential investigation in cancer research is frequently seen as high-risk potential since the clinical applications give a unique detail about the scientific journal . From many cases, information is gathered for examining cancer cells, not as it made stride our understanding of the infection but it is necessary for the improvement of clinical progress which is more useful to the patients, as well as to theimmunotherapy and cancer immunizations outlines.

In many cases,the abilityof almost all the results of fundamental analysis about the cancer researchers are about the moderately small subsequence from so many sources, so that government financing for cancer research analysis about is critical. Collaborating over disciplines is progressively essential to get better vital instrument in cancer. In this manner, a few examiners may get to create apparatus and procedures for sharing and communicating their investigation through a scientific paper .

There are five steps to write an active cancer research proposal

• Preparation
• Development
• Specific points
• Background and importance
• Research plan and strategies
• Preparation:

This is the first step in writing a research paper. Identification of research journals . How long it would take to complete the process, what level of financing it would require, and finding of potential for particular compounds. 

• Development:

Given application undergo through these sequences 1. Unique 2. Presentation 3. Particular aims, 4. Significant 5. Investigation or research plans 6. Budget 7. Biographical sketch

• Specific point:

The particular point/ specific point is the question, speculations, or generally speculations that the research is looking to address or test. The author undergoes to represent the long-term objective or short-term objective, reasonable or extremely reasonable as well as particular point should aim the scientific research paper .

            Cancer research may address extensive and complex questions that are not continuously fully expressed. The author can take critical bits of knowledge that may rise amid the course of the study that will direct theproject in future headings.

This area briefly explains about the publication, critically evaluates existing information, and particularly distinguishes the reports which the project intends to fill. Briefly states the significance and healthy importance of the research paper described within the application by relating the particular points to the overall long-term objective. Here the author has the opportunity to show information of the field, the capacity to analyse the existing research about critically, and to appear how the proposed work will expand a investigate zone.

Sketch the research about plan and method to be utilized to achieve the specific aims of the development. Incorporate how the information will be collected, analysed and interpreted. Sketch any unused strategy and its advantages over existing methodology . Talk about the potential trouble and barrier of the proposed procedures and elective approaches to attain the points. As a part of this research area which gives a conditional arrangement or timetable for the extension point out.

Conclusion:

In cancer research and therapies, there are so many advancements which help to fasten the technology and record-breaking. There are so many limitations like drug properties, industrial scale-up and stability of drugs to a clinical trial. We are going with you through the whole circulating stages we help restorative specialists, backup, healing centres, pharma and apparatus producers in their journey for a solid collaboration. We have specialists over subjects such as life science, therapeutic and innovation

References:

• International Committee of Medical Journal Editors. Recommendations for the conduct, reporting, editing, and publication of scholarly work in medical journals. 2014. (accessed November 2016).
• Gopen G & Swan J. The science of scientific writing.  Am Sci . 1990; 78:550–558. (accessed November 2016)
•  Fisher JP, Jansen JA, Johnson PC  et al . Guidelines for writing a research article for publication. Mary Ann Liebert Inc. (accessed November 2016)
• World Association of Medical Editors. Professionalism Code of Conduct. 2016
• Bossuyt PM, Reitsma JB, Bruns DE  et al . Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative.  Ann Int Med  2003; 138:40–44.

pubrica-academy

Related posts.

Statistical analyses of case-control studies

PUB - Selecting material (e.g. excipient, active pharmaceutical ingredient) for drug development

Selecting material (e.g. excipient, active pharmaceutical ingredient, packaging material) for drug development

PUB - Health Economics of Data Modeling

Health economics in clinical trials

Comments are closed.

• Policy Guidance
• Submitting Data
• Accessing Data
• About the Genomic Data Sharing (GDS) Policy
• Key Documents
• Preparing Genomic Data
• Extramural Grantees
• Non-NCI Funded Investigators
• Intramural Investigators
• Accessing Genomic Data
• Genomic Data Sharing Policy Contact Information
• Data Standards Services
• Cloud Resources
• Data Commons Framework
• Repositories
• ARPA-H BDF Toolbox
• Accelerating Therapeutics for Opportunities in Medicine (ATOM)
• NCI-DOE Collaboration AI/ML Resources
• NCI-DOE Publications
• U.S.-EU Artificial Intelligence Administrative Arrangement
• NCI Data Catalog
• CDISC Terminology
• FDA Terminology
• NCPDP Terminology
• Pediatric Terminology
• Metadata for Cancer Research
• Informatics Technology for Cancer Research (ITCR) Tools
• Generating and Collecting Data
• Cleaning Data
• Exploring and Analyzing Data
• Predictive Modeling
• Visualizing Data
• Sharing Data
• Cancer Data Science Course
• Training Guide Library
• Cancer Data Science Pulse Blog
• Data Science Seminar Series
• Jobs and Fellowships
• Contact CBIIT
• Organization
• CBIIT Director
• Staff Directory
• Application Support
• Genomic Data Sharing
• NCI-Department of Energy Collaborations
• Cancer Vocabulary
• Learn About Cancer Data Science
• Improve My Data Science Skills

Submit Your Cancer Research Proposal to NIH’s New Multimodal AI Funding Opportunity

Do you have an idea for advancing health research (including cancer research) through multimodal artificial intelligence (AI)? Would you like to collaborate with researchers who are experts in biomedical research, ethics, and quantitative research (such as computer sciences, applied mathematics, and AI)? If so, apply for this Research Opportunity Announcement (ROA)! Tackle biomedical challenges by using collaborative and participatory approaches that involve multiple modes of AI.

Through the Advancing Health Research through Ethical, Multimodal AI Initiative , NIH hopes to create better AI approaches to model, interpret, and predict complex, multiscale biological, behavioral, and health systems. This will not only improve our understanding of health but also our ability to identify and treat human illnesses, such as cancer.

You have a chance to work with a diverse group of research experts and end users alike to develop and test new models using ethical, multimodal AI technologies. You can help NIH build a portfolio of projects that use ethics-driven AI to address systems-level biomedical challenges with a combination of data types. To ensure effective collaboration, make sure your project employs a co-design approach that involves continual and iterative feedback among different aspects of the project (including model development, data preparation, and data collection ).

If you have any questions about this ROA, you can send an email to program officials .

Enter the characters shown in the image.

SUBSCRIBE TO UPDATES

Help us help you: take this 5-minute survey.

We want to know what you want from this website and our weekly email. Your feedback will help us ensure we’re getting you the information you want, how you want it.

Together we are beating cancer

About cancer

Cancer types

• Breast cancer
• Bowel cancer
• Lung cancer
• Prostate cancer

Cancers in general

• Clinical trials

Causes of cancer

Coping with cancer

• Managing symptoms and side effects
• Mental health and cancer
• Money and travel
• Death and dying
• Cancer Chat forum

Health Professionals

• Cancer Statistics
• Cancer Screening
• Learning and Support
• NICE suspected cancer referral guidelines

Get involved

• Make a donation

By cancer type

• Leave a legacy gift
• Donate in Memory

Find an event

• Race for Life
• Charity runs
• Charity walks
• Search events
• Relay For Life
• Volunteer in our shops
• Help at an event
• Help us raise money
• Campaign for us

Do your own fundraising

• Fundraising ideas
• Get a fundraising pack
• Return fundraising money
• Fundraise by cancer type
• Set up a Cancer Research UK Giving Page
• Find a shop or superstore
• Become a partner
• Cancer Research UK for Children & Young People
• Our We Are campaign

Our research

• Brain tumours
• Skin cancer
• All cancer types

By cancer topic

• New treatments
• Cancer biology
• Cancer drugs
• All cancer subjects
• All locations

By Researcher

• Professor Duncan Baird
• Professor Fran Balkwill
• Professor Andrew Biankin
• See all researchers
• Our achievements timeline
• Our research strategy
• Involving animals in research

Funding for researchers

Research opportunities

• For discovery researchers
• For clinical researchers
• For population researchers
• In drug discovery & development
• In early detection & diagnosis
• For students & postdocs

Our funding schemes

• Career Development Fellowship
• Discovery Programme Awards
• Clinical Trial Award
• Biology to Prevention Award
• View all schemes and deadlines

Applying for funding

• Start your application online

How to make a successful application

• Funding committees

Successful applicant case studies

How we deliver research

• Our research infrastructure
• Events and conferences
• Our research partnerships
• Facts & figures about our funding
• Develop your research career

Recently funded awards

• Manage your research grant
• Notify us of new publications

Find a shop

• Volunteer in a shop
• Donate goods to a shop
• Our superstores

Shop online

• Wedding favours
• Cancer Care
• Flower Shop

Our eBay store

• Shoes and boots
• Bags and purses
• We beat cancer
• We fundraise
• We develop policy
• Our global role

Our organisation

• Our strategy
• Our Trustees
• CEO and Executive Board
• How we spend your money
• Early careers

Cancer news

• Cancer News
• For Researchers
• For Supporters
• Press office
• Publications
• Update your contact preferences

ABOUT CANCER

GET INVOLVED

NEWS & RESOURCES

FUNDING & RESEARCH

You are here

We fund research that makes a clear link with our research priorities and look for the best researchers in their field.

Below is some simple advice from our research funding team that will help you make a great application. Each funding scheme has its own application guidelines so it's vital that you read these too before submitting an application. If you have any questions about these specific guidelines then you should get in touch with the person who manages that scheme. If you'd like to know more, you can also  read advice from our current grantees .

What you will be judged on

• Relevance to our research priorities - read our Research Strategy and clearly state how your research relates to cancer research. Make sure you read the eligibility information for your chosen scheme.
• The originality of your ideas and proposal - make sure your research is answering an important and valid research question.
• Your knowledge of relevant literature and developments in your area.
• The quality of your experimental design – think about feasibility and identify what could go wrong. Show preliminary data if relevant.
• Value for money – your funding panel will want to know that the money we invest will be spent well. Make sure you leave enough time to budget accurately and that your costs are realistic. You should also justify all your costs.
• Your research team – make sure the people you choose have the right expertise. Check if there are other areas they can help with outside of the obvious scientific requirements of the project. For example, do they have a background in public policy that will help you share your findings?
• You – it’s important the funding panel trust their investment in you. Identify your unique strengths and draw on your previous successes.

Remember, it helps to know your audience. Find out who sits on the funding committee relevant to your scheme and what they’re interested in. They may even be a member of your current institution and you’ll be able to speak to them directly. Take a look at our funding committee pages.

Advice from our decision makers (funding committees)

1. show clearly how the application builds on existing knowledge.

Your research must be based on solid principles.

2. Spend time on the abstract

• Include all aspects of the study so the reviewers can immediately see everything you plan to do.
• Make sure it’s clear, concise, and thorough.

3. Make every step of the methods 100% clear

• Including the procedure, sample size, why you have chosen that sample and how you will collect and analyse the data.
• Make sure you clearly show how your objectives or research questions will be addressed.

4. Tell a coherent, easily understood story

• Why you are doing the study.
• What you plan to do.
• How you will go about this.
• When you plan to do it and timings.
• What the impact will be.
• Who your team are.
• How you will resource the work.

5. Remember that simple ideas appeal

If your plan includes too many studies with too many components the research questions can become lost.

6. Take time on the analysis section

Some grant applications fail through imprecise descriptions of analysis of the data. Make sure you demonstrate your understanding of data, whether it’s statistical or qualitative.

Filling in the online form

• Work with the grants/research office at your host institution – they can offer support and advice, particularly around costing your research proposal.
• Gather relevant additional information, such as ethical/regulatory approval, equipment quotes, letters of support, commercial interactions and other awards. 
• Contact the grants helpline if you have questions about our online grants management system: [email protected] .

Contact the grants team

[email protected]

Find funding

Find a funding opportunity that suits your career and research area.

Search all funding

Find out how our current grantees successfully applied for funding.

Recently funded awards by Cancer Research UK

Find out more

Help elsewhere

NIHR Research Design Service

Health and Care Research Wales: Research Design and Conduct Service

MRC Guidance for complex interventions

• Sample Grant Applications
• Implementation Science
• Funding Opportunities

Several investigators and their organizations agreed to post part of their dissemination and implementation grant applications online. We are grateful to them for letting us provide this resource to the community.

Note: These sample grants predate some recent grants policy changes, including  NIH’s Data Management and Sharing (DMS) Policy  (effective January 25, 2023). Please refer to the  NIH Grants Policy  and  NCI Grants Policy  to ensure your application is in full compliance.

R37: Sustainability Determinants of an Intervention to Identify Clinical Deterioration and Improve Childhood Cancer Survival in Low-Resource Hospitals

Principal investigator.

Asya Agulnik, MD, MPH ST. JUDE CHILDREN'S RESEARCH HOSPITAL*

Virginia McKay, MA, PhD RESEARCH ASSISTANT PROFESSOR*

Award Number

1R37CA276215-01

R21: Policy Implementation Research on Health Benefit Mandates for Fertility Preservation Services to Improve Access to Care in Young Cancer Survivors

Hui-Chun Irene Su, MD, MSCE UNIVERSITY OF CALIFORNIA SAN DIEGO HEALTH*

R21#CA271184-01A1

R01: Establishing Smoke-Free Homes with Families Involved in Child Protective Services: An Effectiveness-Implementation Trial of an Integrated Program

Shannon R. Self-Brown, PhD Georgia State University School of Public Health*

R01#CA248551-01A1

R37: Testing an Adaptive Implementation Strategy to Optimize Delivery of Obesity Prevention Practices in Early Care and Education Settings

Taren Swindle, PhD University of Arkansas for Medical Sciences*

R37#CA252113-01A1

R37: De-implementation of low value castration for men with prostate cancer

Ted Skolarus, MD, MPH, FACS University of Michigan at Ann Arbor*

R37#CA222885-01

R21: Improving HPV Vaccination Using Implementation Strategies in Community Pharmacies

Benjamin Teeter, PhD, MS University of Arkansas for Medical Sciences*

R21#CA231180-01A1

R01: Using Technology to Scale-Up an Occupational Sun Protection Policy Program

David B. Buller, PhD Klein Buendel Inc.*

R01#CA210259-01A1

R01: Implementing Universal Lynch Syndrome Screening across Multiple Healthcare Systems: Identifying Strategies to Facilitate and Maintain Programs in Different Organizational Contexts

Alanna Rahm, PhD Geisinger Clinic*

R01#CA211723-01A1

R01: Implementing Cancer Prevention Using Patient - Provider Clinical Decision Support

Thomas E. Elliott, MD HealthPartners Institute*

R01#CA193396-01A1

R21: Effective Training Models for Implementing Health-Promoting Practices Afterschool

Rebekka Mairghread Lee, ScD Harvard School of Public Health*

R21#CA201567-01A1

R01: Increasing Implementation of Evidence-Based Interventions at Low-Wage Worksites

Margaret Hannon, PhD University of Washington*

R01#CA160217-01A1

Additional Information

We redact some information from these documents, such as budgets, social security numbers, home addresses, and introductions to revised applications. We also only include a copy of the SF 424 R&R Face Page, Project Summary/Abstract (Description), Project Narrative, Specific Aims, and Research Strategy. We do not include other SF 424 (R&R) forms or basic information found in full grant applications, such as performance sites, key personnel, or biographical sketches.

*Institution at time of grant award. **Notice(s) of Funding Opportunities (NOFOs) at the time of grant award that have since expired.

The text of the grant applications is copyrighted. Investigators and others may use the text from these applications only for nonprofit educational purposes provided that the content remains unchanged and that the Principal Investigator(s), their organization(s), and NCI are credited.

Individuals using assistive technology (e.g., screen reader, Braille reader, etc.) who experience difficulty accessing any information should send an email to the IS team ( [email protected] ).

Other Sample Grants

See examples of successfully funded grant applications.

Current Implementation Science Funding Opportunities

Find resources and learn about implementation science funding opportunities such as Dissemination and Implementation Research in Health.

• Public Goods
• Eligibility Requirements
• Application Procedure
• Frequently Asked Questions
• Outcomes of the 2023 CCIS Meeting
• Outcomes of the 2022 CCIS Meeting
• Outcomes of the 2021 CCIS Meeting
• Outcomes of the 2020 ISCC Meeting
• Outcomes of the 2019 ISCC Meeting
• CCIS Action Groups
• Health Equity Toolkit
• ISC3 Centers
• Research Tools
• Practice Tools
• Research-Practice Partnerships
• Ali Abazeed, MPH, MPP
• Annabelle Uy, MS
• Antoinette Percy-Laurry, DrPH, MSPH
• Cynthia A. Vinson, PhD, MPA
• David Chambers, DPhil
• Gila Neta, PhD, MPP
• Laurie Hursting, MA
• Mindy Clyne, MHS, CGC
• Pete DelNero, PhD, MPH
• Sarah Bruce Bernal, MA
• Wynne E. Norton, PhD

Sample Healthcare Delivery Research Grant Applications

The National Cancer Institute (NCI) frequently receives requests for examples of funded grant applications. Several investigators and their organizations agreed to let the Healthcare Delivery Research Program (HDRP) post excerpts of their healthcare delivery research grant applications online.

We are grateful to the investigators and their institutions for allowing us to provide this important resource to the community. We include a copy of the SF 424 R&R Face Page, Project Summary/Abstract (Description), Project Narrative, Specific Aims, and Research Strategy; we do not include other SF 424 (R&R) forms or requisite information found in the full grant application (e.g., performance sites, key personnel, biographical sketches). To maintain confidentiality, we have redacted some information from these documents (e.g., budgets, social security numbers, home addresses, introduction to revised application).

Sample Applications

R01: personalized screening for lung cancer: the importance of co-existing chronic conditions to clinical practice and policy, principal investigator.

Grant Mechanism & Award Number

R01CA249506-01

R01: Predicting and Addressing Colonoscopy Non-adherence in Community Settings

R01CA218923-01A1

R01: Using MOST to EMPOWER: Optimizing an Emotional Regulation Intervention to Enhance Well-being Among Young Adult Cancer Survivors

Principal investigators.

R01CA242849-01

R01: Improving Informal Caregivers' and Cancer Survivors' Psychological Distress, Symptom Management and Health Care Use

R01CA224282-01A1

R03: Statewide Assessment of HPV Vaccination Among Childhood Cancer Survivors

1R03CA216174-01A1

R03: Multi-center Evaluation of Digital Breast Tomosynthesis with Synthesized Two-dimensional Mammography for Breast Cancer Screening

R03CA223725-01

R21: Improving Transition Readiness in Adolescent and Young Adult (AYA) Survivors of Childhood Cancer

R21CA222936-01A1

R50: Natural History of Lung Cancer Diagnosed Within and Across Diverse Health Systems Implementing Lung Cancer Screening

R50CA251966-01

Additional Details

Copyright information.

The text of the grant applications is copyrighted. Investigators and others may use the text from these applications only for nonprofit educational purposes provided that the content remains unchanged and that the Principal Investigator(s), their organization(s), and NCI are credited.

Accessibility

Individuals using assistive technology (e.g., screen reader, Braille reader, etc.) who experience difficulty accessing any information should send an email to the HDRP team ( [email protected] ).

Other Sample Grants

See examples of successfully funded grant applications.

Currently Open Notice of Funding Opportunities Relevant to HDRP

See the currently open notice of funding opportunities (NOFOs) sponsored or co-sponsored by HDRP; other NOFOs relevant to HDRP; and NIH and NCI Parent and Omnibus NOFOs for investigator-initiated research.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Obstet Gynecol Sci
• v.61(3); 2018 May

Proposal for cervical cancer screening in the era of HPV vaccination

Yung-taek ouh.

Department of Obstetrics and Gynecology, Guro Hospital, Korea University College of Medicine, Seoul, Korea.

Jae Kwan Lee

Eradication of cervical cancer involves the expansion of human papillomavirus (HPV) vaccine coverage and the development of efficient screening guidelines that take vaccination into account. In Korea, the HPV National Immunization Program was launched in 2016 and is expected to shift the prevalence of HPV genotypes in the country, among other effects. The experiences of another countries that implement national immunization programs should be applied to Korea. If HPV vaccines spread nationwide with broader coverage, after a few decades, cervical intraepithelial lesions or invasive cancer should become a rare disease, leading to a predictable decrease in the positive predictive value of cervical screening cytology. HPV testing is the primary screening tool for cervical cancer and has replaced traditional cytology-based guidelines. The current screening strategy in Korea does not differentiate women who have received complete vaccination from those who are unvaccinated. However, in the post-vaccination era, newly revised policies will be needed. We also discuss on how to increase the vaccination rate in adolescence.

Introduction

Cervical cancer is the fourth most common female cancer worldwide, with an estimated 265,700 deaths per year, and remains the most common female cancer in 42 countries (primarily developing countries) [ 1 ]. In addition, cervical cancer has relatively early onset, occurring primarily during reproductive ages, and is one of the 3 most common cancers among women under age 45 in most countries [ 2 ]. There has been a lot of effort to prevent cervical cancer through primary screening and human papillomavirus (HPV) vaccination; as a result, the disease has been gradually reduced in several developed countries [ 3 , 4 ]. In Korea, for example, the incidence rate of cervical cancer has gradually decreased to a rate of 9.0 per 10 5 in 2014, compared to 16.3 per 10 5 in 1999 [ 5 ].

HPV has been clearly demonstrated as a cause of invasive cervical cancer [ 6 ]. It is the most common sexually transmitted virus, and the progression of it is unusual in that the greatest prevalence is within 5 years from the initiation of first coitus, then decreases with age [ 7 ]. Most women infected with high-risk HPV self-clear and acquire immunity against certain types. However, in about 15% of HPV infections, the virus persists and induces precancerous lesions or invasive cervical cancer [ 8 ]. HPV 16 and 18 have been the most causative types among high-risk HPV viruses, and up to now those 2 genotypes have accounted for 70% of all cervical cancer [ 9 ]. HPV 6 and 11, which are also covered by the quadrivalent vaccine, are responsible for most anogenital warts [ 10 ].

In a randomized controlled trial, HPV testing in combination with liquid-based cytology or alone was more effective than cytology for cervical cancer screening, although HPV screening might result in over-diagnosis in patients with regressive moderate dysplasia [ 11 ]. The primary HPV DNA test has a higher sensitivity and reproducibility than cervical cytology for detecting cervical intraepithelial lesions [ 12 ]. In the HPV vaccination era, the prevalence of cervical lesions as precancerous lesions or invasive cancer should decrease, and as a result, the HPV test will largely replace cytology for screening [ 13 ].

The introduction of a national HPV immunization program in Korea is expected to make various changes in Korea, including the eradication of specific HPV types and a shift in the distribution of HPV genotypes. As the vaccination rate increases, the prevalence of precancerous cervical lesions and cervical cancer will decrease, which will require revision of screening strategies in the post-vaccination era. Two major strategies for cancer prevention and eradication should be considered in future guidelines. First, the efficiency of screening should be improved through HPV DNA tests or new screening tools. Second, efforts should be made to improve the vaccination rate and coverage ( Fig. 1 ).

Two different strategies against human papillomavirus (HPV) in the era of HPV vaccination.

Effects of HPV vaccination

1. mechanism: antibodies against major l1 capsid proteins.

The HPV vaccine plays both preventive and treatment roles for precancerous lesions or cervical cancer. HPV 16/18 E7 antigen-pulsed dendritic cell vaccination can be used as a treatment option for invasive cervical cancer [ 14 ]. In addition, recurrent laryngeal papillomatosis is treated successfully by HPV vaccination [ 15 , 16 ]. Previous studies have shown that the HPV vaccine produces HPV-specific antibodies against L1 capsid proteins into the cervical epithelium [ 17 ]. Furthermore, HPV vaccination induces T-cell responses and antigen-presenting cells for local cell-mediated immunity, enhancing adaptive immunity [ 18 ]. The major capsid antigen L1 synthesizes virus-like particles, which lead to the production of neutralizing antibodies and a humoral response [ 19 ].

In the United States, the National Center for Health Statistics reported the impact of vaccination on the prevalence of HPV in the population by comparing HPV DNA prevalence in the pre-vaccination era (2003–2006) and vaccination era (2009–2012). They showed a 64% decrease in the prevalence of quadrivalent HPV vaccine types [ 6 , 11 , 16 , 18 ] in women aged 14 to 19 years, and a 34% decrease in women aged 20 to 24 years [ 20 ].

2. HPV vaccine against high-grade cervical intraepithelial neoplasia

Clinical trials to evaluate the HPV vaccine against high-grade cervical intraepithelial lesions, including HPV-023, Patricia, Costa Rica, Future I, II, and {"type":"clinical-trial","attrs":{"text":"NCT00543543","term_id":"NCT00543543"}} NCT00543543 , reached a consensus result of nearly 100% efficacy ( Table 1 ) [ 21 , 22 , 23 , 24 , 25 , 26 ].

RCT, randomized controlled trial; CIN, cervical intraepithelial neoplasia.

a) Efficacy against CIN 2 or more severe lesions.

The HPV vaccine impact monitoring project (HPV-IMPACT) in the United States was a sentinel system for monitoring the impact of HPV vaccination targeting cervical intraepithelial neoplasia (CIN) 2/3 in 18 to 39-year-old women from 2008 to 2012. The authors reported a decrease in screening rates, with the largest decreases among 18 and 20-year-olds, as well as a significant decrease in the incidence of CIN 2+. Nevertheless, an impact of vaccination on declining CIN 2+ was still demonstrated because the decrease in CIN 2+ was larger than the decrease in screening [ 27 ].

A phase 3 double-blind trial, Females United to Unilaterally Reduce Endo/Ectocervical Disease, was conducted to estimate the efficacy of the quadrivalent vaccine against high-grade cervical lesions. Vaccine efficacy for the prevention of CIN 2/3, adenocarcinoma in situ, or cervical cancer was 98.2% (95.89% confidence interval [CI], 86–100) [ 24 ].

3. Seroconversion rate after vaccination

HPV vaccination induces seroconversion in nearly all women who were vaccinated, and titer levels are higher than in women with seroconversion as a consequence of natural infection [ 28 , 29 ]. Although natural infection also induces cell-mediated immunity and protects against the identical HPV type, the seroconversion rate is much lower than HPV vaccination; 60% for HPV 16, 54% for HPV 18, and 69% for HPV 6. Natural infection results in lower titer levels and a delay of about 1 year for seroconversion compared to HPV vaccination [ 30 ]. Although HPV antibodies are sustained for at least 4.5 to 5 years, the sustainability of seropositivity after HPV vaccination has yet to be established since no long-term follow-up data are available [ 31 , 32 ].

4. Impact on HPV distribution

In the era of HPV vaccination, a shift in the prevalence of HPV genotypes is expected. In a German population-based cohort study, a significant decrease in HPV 16, 18, and 31 was found among women aged ≤22 years, compared with women aged 23 to 29 years [ 33 ]. Notably, HPV 31 was reduced via cross-protection. On the other hand, other types not included in the vaccine such as HPV 51, 53, and 56 occurred at a higher percentage in vaccinated women.

In Scotland, a national HPV immunization program was implemented for girls aged 12 and 13 years in 2008, with 90% of all subjects receiving the 3-dose uptake of the bivalent vaccine annually. They demonstrated a significant reduction in the prevalence of HPV 16 and 18, as well as HPV 31, 33, and 45 from a cross-protective effect. HPV 51 and 56 rose as most prevalent HPV genotypes among the HPV types not covered by the vaccine [ 34 ]. The Scottish HPV prevalence in Vaccinated women (SHEVa) study was designed to analyze the impact of vaccination on the performance of HPV testing [ 35 ]. Using clinically validated HPV assays which target both DNA and RNA, there was a 23% to 32% reduction of HPV prevalence in vaccinated women compared to unvaccinated women following the coverage rate was over 90% in the target population. The prevalence of high-risk types other than HPV 16 and 18 was not different between the vaccinated and unvaccinated groups. However, the prevalence of HPV 16 and 18 significantly decreased by 75%.

1. HPV prevalence and type distribution in Korea

In a meta-analysis of HPV type distribution between 1995 and 2007 in Korea, the overall HPV prevalence was 23.9% (95% CI, 23.8–24.1%) in women with normal cytology compared to 95.8% (95% CI, 95.4–96.2%) in women with cervical cancer. HPV 16 was the most common type regardless of cervical disease status. In cervical cancer, HPV 16 accounted for 65.1% of cases, followed by HPV 18 (11.9%), HPV 58 (8.6%), HPV 33 (3.7%), and HPV 52 (3.4%). In high-grade precancerous lesions (CIN 2, 3, and CIS), HPV 58 was the second most common type (14.1%), while HPV 16 accounted for 40.6% [ 36 ]. Likewise, Lee et al. [ 37 ] investigated liquid-based cytology, HPV DNA analysis, and cervical biopsies of 2,358 women, finding that HPV 16 was the most common in any cervical lesions, normal, CIN and squamous cell carcinoma (SCC) lesions. HPV 16 and 58 were the most common in CIN 2/3 patients and HPV 16, 18, 58, and 33 were common in patients with SCC.

Recent studies demonstrated that HPV type distribution has been changing and is different from previous studies, in that HPV 16 is no longer the most common genotype in Korea. A retrospective study in 7,014 women who received a health check-up indicated that the overall positivity for high-risk HPV was 8.4%; HPV 58 (23.8%) was most common, followed by HPV 16 (21.8%) and HPV 52 (16.6%). The type most strongly related to increasing severity of cervical cytology was HPV 56 [ 38 ]. In a single-center study of healthy women who received a health check-up in 2013, HPV 53 (6.5%) was the most common HPV genotype, followed by HPV 52 (6.1%) [ 39 ]. As expected, HPV 16 was the most common type in high-grade CIN lesions. In an analysis of 874 invasive cervical cancer cases over 47 years (1958–2004), HPV 16 accounted for 63.1% of cases, followed by HPV 18 (8.5%), HPV 33 (4.5%), HPV 58 (3.9%), and HPV 31 (3.0%) [ 40 ]. Continued monitoring of the shift in prevalence and distribution of HPV genotypes should continue as vaccination increases.

2. Korean guidelines for cervical cancer screening

The well-established national cancer screening program in Korea has led to 71% and 66% reduced risk of invasive cancer and carcinoma in situ compared to unscreened patients, respectively [ 41 ]. The distribution of age at cervical cancer diagnosis has been shifting, and revised guidelines regarding the timing for cervical cancer screening have been newly implemented in various organizations [ 42 , 43 , 44 ]. Moreover, cervical cancer is definitively influenced by HPV infection, and HPV tests have emerged as important screening tools for precancerous lesions and cervical cancer. Therefore, the practice guidelines for the early detection of cervical cancer by Korean Society of Gynecologic Oncology recommended the HPV DNA test in combination with a cervical cytology test is recommended for women aged ≥30 years old. The screening interval can be extended to 2 years if both tests are negative [ 45 ]. Because the mortality of cervical cancer in Korea and other countries increases with age, the recommendation was made to end cervical cancer screening after the age of 74 [ 46 ]. Within the guidelines, no special considerations were specified for HPV-vaccinated women.

3. HPV vaccination rate in Korea in the present and future

The Korean National Immunization Program (NIP) for HPV was first implemented in June 2016 for girls 11–12 years of age with a 2-dose schedule. Of the 464,932 total subjects aged 11–12 years, 232,303 (50.0%) girls initiated vaccination in the first year of the NIP, especially during the vacation period of July (8.3%), August (9.1%), and December (16.6%) ( Fig. 2 ). Initiation of vaccination rates of girls born in 2004 were 86.3% in Gokseong, a county in South Jeolla, with a highly cooperative public health center and school-based vaccination program [ 47 ]. Regional disparities in HPV vaccination rate were reported as a maximum of 11% points up to June 2017 [ 48 ]. The greatest success was found when public health centers contacted the parents of girls, and they subsequently encouraged children to participate in the vaccination program. Educational newsletters handed out at school also helped enhance the vaccination rate in certain counties. In spite of these efforts, according to the latest analysis in June 2017, nationwide initiation rates were only 35.7% among girls born in 2004 and 2005 [ 49 ].

The monthly number of human papillomavirus vaccination rates in 2016. The data contained only from June to December because the Korean National Immunization Program for HPV was first implemented in June 2016 for girls 11–12 years of age with a 2-dose schedule. The vaccination rates were relatively higher during vacation period (July, August, and December).

4. Future strategies

Although various randomized controlled trials around the world have described the efficacy and impacts of HPV vaccination, the complete effect on future strategies for the prevention of cervical cancer remains undefined. Because the oncogenesis of HPV infection is slow progression from CIN to cervical cancer, it will take decades to thoroughly analyze the effects of vaccination on the prevalence of HPV and incidence of cervical cancer. In terms of immunology, the long-term effects of seropositivity and clinical protection following HPV vaccination should be studied with more vaccinated women, although antibody responses to HPV vaccination have been observed in previous studies [ 26 ].

1) The need for cervical cancer screening

As shown in a German population-based study, there has been a shift in the distribution of HPV types that are not included in the vaccine in the post-HPV vaccination era [ 33 ]. Vaccination for HPV 16/18 had a cross-protective effect against 4 non-vaccine HPV types (HPV 31, 33, 45, and 51) in the randomized, double-blind trial [ 50 ]. Induced cross-reactive T-cells and specific antibodies to other HPV genotypes not included in the quadrivalent HPV vaccine, such as HPV 31, 33, and 45, have been demonstrated in previous studies, and the prevalence of HPV 31, 33, and 45 is also declining [ 51 ]. Debates continue on whether the bivalent HPV vaccine is cross-protective against HPV 6 and HPV 11 [ 52 , 53 , 54 ]. For these reasons, screening for HPV DNA is still important for the time being, because none of the currently available vaccines has been proven to provide complete protection against all high-risk HPV genotypes.

As described above, there was a 75% reduction of HPV 16 and 18 in Scotland following a national vaccination program with a coverage rate of over 90% [ 35 ]. Nevertheless, other high-risk HPV types were prevalent in vaccinated women with low grade cervical lesions. The phenomenon of increasing non-HPV 16/18 genotypes highlights the importance of utilizing different HPV detection strategies in women who have been vaccinated and those who are unvaccinated. However, in a recent randomized trial evaluating type replacement after HPV vaccination, HPV type replacement did not occur in vaccinated population within 4 years, and the authors predicted that it was unlikely to occur in vaccinated populations [ 55 ].

2) Reassessment of HPV screening initiation age and intervals (distinguishing between vaccinated and unvaccinated women)

Since HPV 16 and 18 positivity is expected to decline rapidly over the decades following implementation of a national immunization program, specific screening protocols and intervals should be implemented for vaccinated groups. There have been some studies about the correlation between HPV vaccination and changes in cervical cancer screening rates, although none have focused on Korea. In spite of concerns that women who have been vaccinated would be less likely to seek out cervical cancer screening, women who received the HPV vaccine more often received cervical cancer screening than those who had not been vaccinated [ 56 , 57 ]. Research on awareness of cervical cancer screening for women who have been vaccinated is needed in Korea, as well as a serious discussion about strategies to induce unvaccinated women to seek screening.

In the era of vaccination, we should provide different strategies for cervical cancer screening. HPV 16 and 18 are expected to nearly disappear; as a consequence, the positivity of screening tests would be lower than 30% [ 58 ]. Furthermore, the prevalence of lesions more advanced than severe dysplasia would also be reduced more than half, making screening less predictive and decreasing the benefit-harm ratio [ 59 ]. Cervical cancer caused by HPV types other than HPV 16 and 18 appears at a median of 5 years later than that caused by HPV 16 and 18. In particular, short term persistence of HPV 16 infection more strongly predicts a subsequent moderate dysplasia or more advanced pathology compared to other HPV genotypes [ 60 ]. Although there are not enough data to suggest revised recommendations other than older initial screening age and extended screening intervals, one option would be routine screening with HPV testing at 30, 45, and 60 years of age for women who were fully vaccinated before first sexual contact [ 61 ]. It would be more efficient to provide separate screening guidelines for vaccinated and unvaccinated women. In Italy, primary HPV screening is recommended starting at 30 years and at 5-year intervals for vaccinated women who were vaccinated in 2007/2008 and became 25 years old in 2017 [ 62 ]. An optimal cervical cancer screening model for women who have been vaccinated with all 3 doses was proposed in 2017 from a US model based-analysis of benefits and costs. They suggested that screening could be modified to start later with decreased frequency, with either cervical cytology or HPV testing alone every 5 years starting at age 25 or 30, and only primary HPV testing recommended every 10 years starting at age 30 or 35 for women vaccinated with the nonavalent vaccine [ 63 ].

3) Shift in screening from cytology or cytology/HPV to HPV alone

In April 2014, an HPV DNA test was approved as a primary screening tool by the Food and Drug Administration. Nevertheless, further investigation is needed to evaluate the efficacy of using only an HPV DNA test and the adverse effects of increased false-positivity. The issues of the primary HPV screening test are to distinguish high-risk HPV positive with ≥CIN 2 from patients with transient positivity. There will be an increase in false positivity due to high-risk HPV infection without ≥CIN 2. As the number of patient with transient high-risk HPV infection increases, unnecessary follow-up and cost burdens will be a problem to be solved [ 64 ]. The positive predictive value of cervical cytology for cervical cancer screening is expected to decrease along with the incidence of precancerous or cancerous lesions in the cervix after implementation of the NIP of HPV. Normal cervical cytology will correspondingly increase, leading to an increase in false negative results and a decrease in the sensitivity of cytology, further reducing the value of cytology as screening tool [ 65 , 66 ]. However, endocervical adenocarcinoma with gastric type in which the HPV was rarely detected could be a potential pitfall of HPV vaccination and HPV DNA testing although the incidence was low [ 67 ].

A retrospective population-based cohort study documented the effect of HPV vaccination on abnormal cervical cytology in women born between 1988 and 1993, using data from the Scottish Cervical Screening Program [ 68 ]. The authors observed a significant reduction in positive predictive value and abnormal predictive values for detecting CIN 2+ in vaccinated women, as well as a significant reduction in abnormal cytology.

4) New screening tools

New screening tools are an alternative in the context of a lower prevalence of HPV-positive tests and related abnormal cytology of the cervix. Although various new tools have been proposed with more specific markers, additional verification and certification are needed before commercialization. First, HPV E6 protein detection is more specific than the HPV DNA test for high-grade cervical lesions, and so far at a lower cost. This test targets HPV 16, 18, and 45 and has the greatest positive values for detecting severe dysplasia or more severe lesions compared to high-risk HPV DNA testing [ 69 , 70 ]. Second, p16 INK4a immunohistochemistry is useful for identifying moderate dysplasia or more severe lesions in high-risk HPV-positive women [ 71 ]. In a study of the endpoint of moderate dysplasia or more severe lesions in HPV-positive women, the sensitivity of p16 INK4a immunohistochemistry was 88% (81 of 92; 95% CI, 80–94) and specificity was 61% (633 of 1,045; 95% CI, 57–64) without an increase in the implementation of colposcopy [ 72 ]. Finally, p16/Ki-67 dual-stained cytology is more sensitive than Pap cytology for detecting high-grade CIN. Even with normal cytology, p16/Ki-67 dual-stained cytology detected more than two-thirds of severe dysplasia lesions in women with high-risk HPV and helped select colposcopy referral patients [ 73 , 74 , 75 ].

5) How to increase vaccination coverage levels (i.e., school-based vaccination)

Because 2 doses of the HPV vaccine provided more compliance than 3 doses, 2 doses tended to increase the rate of vaccination completion. In a combined analysis of data from the Costa Rica Vaccine and PATRICIA trials, the efficacy of 2 dose-vaccination was evaluated. Both 3 doses and fewer than 3 doses of bivalent vaccine showed comparable efficacy 4 years following vaccination of women between 15 and 25 years old. Cross-protective activity against HPV 31, 33, and 45 was obtained only for cases in which the interval of the 2 doses was 6 months [ 76 ]. In a cluster-randomized trial, the vaccination coverage rate was increased by education delivered to mothers of adolescent daughters [ 77 ]. In addition, the vaccination and completion rate was improved by consistent recommendations from health care providers [ 78 ]. Social efforts such as educating providers and clinic-specific feedback to encourage patients will increase vaccination rates.

To eradicate cervical cancer in an era when HPV infection and related diseases rarely occur, screening methods must account for vaccine programs. Primary HPV DNA tests will be substituted for conventional Pap smears in screening tests, allowing Pap smears to be applied only to HPV-positive women. Education of patients and providers, an effective vaccination program to increase vaccine coverage rate, and school-based encouragement can help eliminate HPV-related disease and invasive cervical cancer.

In Korea, a national immunization program has been implemented since 2016, and strategies to further increase the vaccination rate should involve the government, schools, and parents. Because HPV vaccines do not cover all types of high-risk HPV, screening for precancerous lesions and cervical cancer will not be eliminated. In the decades following a national HPV vaccine program with a high coverage rate, existing screening strategies based on primary cytology such as Pap smear should be reviewed, because the low prevalence of abnormal cytology of the cervix will make screening less cost-effective and inefficient. Primary HPV testing will play an important role as a screening test and cytology should be reserved for women with an HPV positive test. In addition, reassessment of HPV screening initiation age and intervals that distinguish vaccinated women from unvaccinated women should be discussed in the near future.

Conflict of interest: No potential conflict of interest relevant to this article was reported.

Stanford Cancer Institute

Search stanford cancer institute, upstream research center pilot proposals.

Deadline: November 15, 2024

The Upstream Research Center, co-led by Stanford, UC Davis, and UCSF, is pleased to release the third round of requests for pilot proposals. Upstream is awarding up to $75,000 each for three impact-focused research projects to reduce cancer inequities due to structural and social determinants, including, but not limited to, structural racism, poverty, income inequality, climate change, food insecurity, social isolation, and/or housing insecurity. Projects must focus on research relevant to exposures experienced in persistent poverty areas in Northern California.

Eligibility:

• Community organizations
• Stanford, UC Davis, UCSF PI-eligible faculty and postdoctoral scholars

Amount of Funding:

• Awards will be granted for one year and up to $75,000 in direct costs..
• We anticipate making three awards. At least one award will support preparation for an intervention study.
• June 18 from 4:00 - 5:00 PM Pacific Time: Informational session
• November 15, 2024: Proposals due
• May 1, 2025 - April 30, 2026: Funding period

Visit https://med.stanford.edu/UPSTREAM/pilot-grants.html for more information and to register for the info session.

• Patient Care
• Clinical Trials
• Health Equity
• Shared Resources

Stanford Medicine

Health care.

©2024 Stanford Medicine

Leading Change in Cancer Clinical Research, Because Our Patients Can’t Wait

May 31, 2024 , by W. Kimryn Rathmell, M.D., Ph.D., and Shaalan Beg, M.D.

Greater use of technologies that can increase participation in cancer clinical trials is just one of the innovations that can help overcome some of the bottlenecks holding up progress in clinical research. 

Thanks to advances in technology, data science, and infrastructure, the pace of discovery and innovation in cancer research has accelerated, producing an impressive range of potential new treatments and other interventions that are being tested in clinical studies . The extent of the innovative ideas that might help people live longer, improve our ability to detect cancer early, or otherwise transform care is staggering. 

Our understanding of tumor biology is also evolving, and those gains in knowledge are being translated into the continued discovery of targets for potential interventions  and the development of novel types of treatments. Some of these therapies are producing unprecedented clinical responses  in studies, including in traditionally difficult-to-treat cancers. 

These advances have contributed to a record number of Food and Drug Administration (FDA) approvals in recent years with, arguably, the most notable approvals being those for drugs that can be used for any cancer, regardless of where it is in the body . 

In some instances, the activity of new agents has been so profound that clinical investigators are having to rethink their criteria for implementation in patient care and their definitions of treatment response. 

For example, although HER2 has been a known therapeutic target in breast cancer for many decades, the new antibody-drug conjugates  (ADCs) that target HER2 have proven to be vastly more effective than the original HER2-targeted therapies. This has forced researchers to rethink fundamental questions about how these ADCs are used in patient care: Can they be effective in people whose tumors have lower expression of HER2 than we previously thought was needed ? And, if so, do we need to redefine how we classify HER2-positive cancer? 

As more innovative therapies like ADCs hit the clinic at a far more rapid cadence than ever before, the research community is being inundated with such fundamentally important questions.

However, the remarkable progress we're experiencing with novel new therapies is tempered by a critical bottleneck: the clinical research infrastructure can’t be expected to keep pace in this new landscape. 

Currently, many studies struggle to enroll enough participants. At the same time, there are patients who don’t have ready access to studies from which they might benefit. Furthermore, ideas researchers have today for studies of innovative new interventions might not come to fruition for 2 or 3 years, or even longer—years that people with cancer don’t have. 

The key to overcoming this bottleneck is to invite innovation to help reshape our clinical trials infrastructure. And here’s how we plan to accomplish that.

Testing Innovation in Cancer Clinical Trials

A transformation in cancer clinical research is already underway. That transformation has been led in part by the success of novel precision oncology approaches, such as those tested in the NCI-MATCH trial .

This innovative study ushered in novel ways of recruiting participants and involving oncologists at centers big and small. And NCI-MATCH has spawned several successor studies that are incorporating and building on its innovations and achievements.

An innovation that emerged from the COVID pandemic was the increase of remote work, even in the clinical trials domain. Indeed, staffing shortages have caused participation in NCI-funded trials to decline. In response, NCI is piloting a Virtual Clinical Trials Office to offer remote support staff to participating study sites. This support staff includes research nurses, clinical research associates, and data specialists, all of whom will help NCI-Designated Cancer Centers and community practices engaged in clinical research activities.

Such technology-enabled services can allow us to reimagine how clinical trials are designed and run. This includes developing technologies and processes for remotely identifying clinical trial participants, shipping medications to participants at home, having imaging performed in the health care settings where our patients live, and empowering local physicians to participate in clinical trials.

We also need mechanisms to test and implement innovations in designing and conducting clinical studies. 

The Pragmatica-Lung Cancer Treatment Trial , an innovative phase 3 study launched by  NCI’s National Clinical Trials Network (NCTN) , was designed to be easy to launch, enroll participants, and interpret its results. 

NCI recently established Clinical Trials Innovation Unit (CTIU) to pressure test a variety of innovations. The CTIU, which includes leadership from FDA and NCTN, is already working on future innovations, including those that will streamline data collection and apply novel approaches to clinical studies, all with the goal of making them less burdensome to run and easier for patients to participate.

Data-Driven Solutions

The era of data-driven health care is here, providing still more opportunities to transform cancer clinical research. 

The emergence of artificial intelligence (AI) solutions, large language models, and informatics brings real potential for wholesale changes in how we match patients to clinical studies, assess side effects, and monitor events like disease progression. 

Recognizing this potential, NCI is offering funding opportunities and other resources that will fuel the development of AI tools for clinical research, allow us to carefully test their usefulness, and ultimately deploy them across the oncology community. 

Creating Partnerships and Expanding Health Equity

To be sure, none of this will be, or can be, done by NCI alone. All these innovations require partnerships. We will increase our engagement with partners in the public- and private-sectors, including other government agencies and nonprofits. 

That includes high-level engagement with the Office of the National Coordinator for Health Information Technology (ONC), with input from FDA, Centers for Medicare & Medicaid Services, and Centers for Disease Control and Prevention.

Dr. W. Kimryn Rathmell, M.D., Ph.D.

NCI Director

One example of such a partnership is the USCDI+ Cancer program . Conducted under the auspices of the ONC, this program will further the aims of the White House's reignited Cancer Moonshot SM by encouraging the adoption and utilization of interoperable cancer health IT standards, providing resources to support cancer-specific use cases, and promoting alignment between federal partners. 

And just as importantly, the new partnerships we create must include those with patients, advocates, and communities in ways we have never considered before.

A central feature of this community engagement must involve intentional efforts to expand health equity, to create study designs that are inclusive and culturally appropriate. Far too many marginalized communities and populations today are further harmed by studies that fail to provide findings that apply to their unique situations and needs.

Very importantly, the future will require educating our next generation of clinical investigators and empowering them with the tools that enable new ways of managing clinical studies. By supporting initiatives spearheaded by FDA and professional groups like the American Society of Clinical Oncology, NCI is making it easier for community oncologists to participate in clinical trials and helping clarify previously misunderstood regulatory requirements. 

These efforts must also ensure that we have a clinical research workforce that is representative of the people it is intended to serve. Far too many structural barriers have prevented this from taking place in the past, and it’s time for that to change. 

Expanding our capacity doesn’t mean doing more of the same, it means challenging ourselves to work differently. This will let us move forward to a new state, one in which clinical research is integrated in everyday practice. It is only with more strategic partnerships and increased inclusivity that we can open the doors to seeing clinical investigation in new ways, with new standards for success.

A Collaborative Effort

Shaalan Beg, M.D.

Senior Advisor for Clinical Research

To make the kind of progress we all desire, we have to recognize that our clinical studies system needs to evolve.

There was a time when taking years to design, launch, and complete a clinical trial was acceptable. It isn’t acceptable anymore. We are in an era where we have the tools and the research talent to make far more rapid progress than we have in the past. 

And we can do that by engaging with many different communities and stakeholders in unique and dynamic ways—making them partners in our effort to end cancer as we know it.

Together, our task is to capitalize on this work so we can move faster and enable cutting-edge research that benefits as many people as possible. 

We also know that there are more good ideas in this space, and part of this transformation includes grass roots efforts to drive systemic change. So, we encourage you to share your ideas on how we can transform clinical research. Because achieving this goal can’t be done by any one group alone. We are all in this together. 

Featured Posts

March 27, 2024, by Edward Winstead

March 21, 2024, by Elia Ben-Ari

March 5, 2024, by Carmen Phillips

• Biology of Cancer
• Cancer Risk
• Childhood Cancer
• Clinical Trial Results
• Disparities
• FDA Approvals
• Global Health
• Leadership & Expert Views
• Screening & Early Detection
• Survivorship & Supportive Care
• February (6)
• January (6)
• December (7)
• November (6)
• October (7)
• September (7)
• February (7)
• November (7)
• October (5)
• September (6)
• November (4)
• September (9)
• February (5)
• October (8)
• January (7)
• December (6)
• September (8)
• February (9)
• December (9)
• November (9)
• October (9)
• September (11)
• February (11)
• January (10)

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• FROM THE ANALYST'S COUCH
• 31 May 2024

The changing landscape of cancer cell therapies: clinical trials and real-world data

• Ana Rosa Saez-Ibañez 0 ,
• Samik Upadhaya 1 ,
• Tanya Partridge 2 ,
• Daniel Winkelman 3 ,
• Diego Correa 4 &
• Jay Campbell 5

Anna-Maria Kellen Clinical Accelerator, Cancer Research Institute, New York, NY, USA.

You can also search for this author in PubMed   Google Scholar

IQVIA, Durham, NC, USA.

Since the first CAR-T cell product was approved by the FDA in 2017, five additional CAR-T cell products have reached the market, all of which target CD19 or BCMA. These products have gathered 14 approvals in different haematological malignancies and some of them have moved to earlier lines of therapy, expanding their target population. Moreover, earlier this year, lifileucel, a non-genetically modified tumour-infiltrating lymphocyte (TIL) therapy, became the first FDA-approved cell therapy product for a solid tumour (metastatic melanoma). Furthermore, an engineered cell therapy product, the T-cell-receptor (TCR)-based therapy afamitresgene autoleucel, may receive approval later this year for the treatment of advanced synovial sarcoma.

However, despite this growth, the cancer cell therapy space faces challenges related to cell persistence, effective targeting of solid tumours and product manufacturing, among others, and intense research is needed to overcome these. Here, we provide an updated analysis of the cell therapy landscape in oncology, including clinical research and real-world data on the use and implementation of this modality.

Cell therapy clinical trial landscape

As of March 2024 and since records began in 1986, there are 5,639 interventional cancer cell therapy clinical trials registered in the CRI’s Immuno-oncology (IO) Intelligence database (Supplementary Fig. 1). Of these, 1,791 trials have already been completed and 2,306 are ongoing (Fig. 1a). Almost 2,700 unique cell therapy products are included in these trials. The number of unique assets tested per year increased to 433 in 2021 and decreased to 409 in 2023 (Supplementary Fig. 2). Of the 2,306 ongoing trials, 96 are testing already approved CAR-T or TIL products (Supplementary Fig. 3).

Fig. 1 | Global landscape of oncology cell therapy trials. a , Full database of oncology cell therapy trials, by status, as of March 2024. b , Number of trials by phase and trial start date. c , Number of trials by cell therapy modality and trial start date. d , Breakdown of the “Other T cells” category from panel c to show contained subcategories of T cell products. The total number of trials per year in panels c and d does not correspond to the number of unique trials on a given year (trials testing more than one cell therapy modality are counted once for each modality used). In all panels, % indicates year-over-year growth.

The number of new cell therapy trials has decreased in the past two years . Our analysis of changes in the cell therapy landscape over the past five years shows that the number of new trials peaked in 2021 and has since decreased by 3.9% in 2022 (led by a 10.5% reduction in phase II trials) and by 4.3% in 2023 (led by a 24.3% decrease in phase I studies). Despite this overall reduction, phase III trials have grown by 33.3% and 43.8% in both years, respectively, and the total number of new trials in 2022–2023 still exceeds the number in 2019–2020 (Fig. 1b). Notably, the reduction in overall trials is tied to trials sponsored by institution or government rather than company-sponsored trials (Supplementary Fig. 4).

To better understand the observed changes, we broke down trial data by indications, cell therapy modalities and targets. These analyses show that cell therapy clinical research has decreased the most in haematological malignancies and gastrointestinal cancers (–9.1% and –4.1% in 2023 compared to 2022, respectively), whereas their use has gone up in central nervous system (CNS) tumours (25.0%), respiratory cancer (90.0%) and mixed solid tumours (3.5%) trials (Supplementary Fig. 5). A broader classification of indications into solid and haematological malignancies shows that cell therapies for solid tumours have continuously grown since 2020, and in 2023 they comprised 53.4% of all new cell therapy trials (Supplementary Fig. 5).

Trends in cell therapy modalities and targeted proteins. Further analysis of this data reveals that in 2023, cell-based cancer vaccines, CAR-NK cells and bacteria-based therapeutics grew relative to 2022 (50.0%, 17.4% and 4.9%, respectively), whereas CAR-T cells and other T-cell products reduced their share in the space (–15.1% and –19.3%, respectively) (Fig. 1c). This is the first time we observe a decrease in new CAR-T cell therapy trials, across both solid and haematological malignancies (Supplementary Fig. 6), even though this is still the dominant cell therapy modality in the IO space. Despite this general reduction, the number of CAR-T cell and other T cell trials has gone up in CNS tumours (27.3% and 50%, respectively) (Supplementary Fig. 7). A closer look at the other subtypes of T cell-based therapeutics shows a sharp growth of gamma-delta TCR-T cells (100% over the prior year), although the fraction of studies using this cell type is still relatively small (Fig. 1d).

When classifying cell therapies by source, our analysis shows that allogeneic products lost ground in 2023, with a 14.7% overall reduction relative to 2022, versus a 1.5% growth in autologous therapies over the same timeframe. Reduction in allogeneic CAR-T cell therapies is more dramatic, with a 42.1% drop in trials in the past year. Notably, 2023 saw the first in vivo CAR-T cell therapy entering the clinic (Supplementary Fig. 8).

Regarding targets, the most common proteins are still CD19, BCMA and CD22, but their use has decreased in the past year (–15.4%, –3.7% and –60.0%, respectively). By contrast, other targets have increased their presence, such as CD7 (33.3%), HER2 (14.3%) and NKG2D (233.3%) (Supplementary Fig. 9). The diversity of targets in the space has also changed over time, growing from 87 to 94 unique targets from 2022 to 2023 (Supplementary Fig. 10). Supplementary Fig. 11 shows a breakdown of targets by cell therapy modality.

Real-world use of CAR-T cell therapies

CAR-T cell therapies have the potential to revolutionize cancer treatment, but our last landscape update reported in 2022 identified several barriers that dampen the real-world use of this modality, such as cost, slot availability and manufacturing complications. To evaluate the evolution of CAR-T cell therapy implementation in the clinic over the past years, we leveraged IQVIA’s CAR-T Cell Center Insights survey data, exploring current barriers that prevent patients referred to CAR-T cell therapy centres receiving treatment. We also compared the new results with those presented in our 2022 publication ( Nat. Rev. Drug Disc. 21 , 631–632; 2022).

According to IQVIA, on average, 38% of referred patients do not receive CAR-T cell therapy. Oncologists at CAR-T cell therapy centres in the USA ( N = 51, one responder per centre) were surveyed between 1 October and 31 December 2023, and asked for the reasons behind this. The results of this survey indicate that the primary reasons why referred patients did not receive CAR-T cell therapies were disease progression (45%), patient choice (43%) and patient eligibility (41%), although less oncologists identified these as decisive factors than in the Q4 2021 survey (54%, 54% and 63%, respectively). Also, product cost has gone from being an important factor for 65% of surveyed oncologists in 2021 to only 37% of them in 2023. Notably 39% of surveyed oncologists highlighted the current availability of bispecific antibodies against the same targets and indications as a reason to not proceed with a CAR-T cell treatment (Supplementary Fig. 12).

Importantly, slot availability (25%) and manufacturing issues (16%) have become less of a barrier for patient treatment in comparison to the 2021 survey (31% and 27%, respectively) indicating an improvement on logistics constraints over the past two years. Only 12% of surveyed oncologists identified availability of treatment beds at CAR-T cell treatment centres as a barrier to treatment (Supplementary Fig. 12). Indeed, we observed that the number of CAR-T cell treatment centres in the USA has continuously increased over the past five years, from 88 in 2018 to 198 in 2023. Of all referrals in IQVIA’s dataset from Q4 2023, most oncologists sent patients to a CAR-T cell therapy centre located as far as 31 miles away from their clinical practice. This means that, on average, patients travel around 2.5 hours to receive treatment (Supplementary Fig. 13).

Conclusions and future directions

Our analysis of cell therapy trials in oncology shows that clinical research in this field has decelerated in 2022 and 2023, with fewer new trials than in 2021 but still above pre-2021 numbers. Although CAR-T cells and other T-cell products are still the largest categories in the space, they have experienced the sharpest decline, whereas NK cells and bacteria-based therapies have grown both in 2022 and 2023. This may indicate a diversification of the field in terms of treatment modalities. We observe a similar effect on targets, where the total pool keeps growing whereas the research on CD19, BCMA and CD22 decreases. These may be healthy signs of continued discovery linked to a reduction of duplicative efforts in the space.

New cell therapy trials have decreased in the past two years, but this may not be due to field-specific factors but rather to the general downturn in the biopharma industry in recent years. In fact, a January 2024 IQVIA Pharma Deals analysis shows that despite the observed shrinkage, cell therapy oncology deals represent a larger share of all life sciences deals in 2023 than in any other year in the past decade (Supplementary Fig. 14).

Another factor that may be contributing is the growing interest in cell therapies in non-oncology indications such as autoimmune, cardiac and infectious diseases, with gene-modified cell therapy trials in autoimmune disorders increasing by almost fourfold between 2021 and 2023 (Supplementary Fig. 15). Although the number of trials in non-oncology indications is still relatively low, this data may suggest a potential interplay, with trials across different indications competing for shared manufacturing and treatment site resources. Even so, the barriers to receive CAR-T cell therapies have experienced a considerable reduction since 2021. It will be interesting to see how the CAR-T cell therapy space adapts to a growing landscape of addressable indications and to a rising number of approvals in earlier lines of haematological indications. Continued monitoring of the cell therapy landscape, from clinical research to real-world usage, will be vital to understand the evolving trends in the space and optimize efforts to make these therapies easily available to all patients in need.

doi: https://doi.org/10.1038/d41573-024-00094-4

Supplementary Information

• Supplementary figures

Competing Interests

The authors declare no competing interests.

Professor/Associate Professor/Assistant Professor/Senior Lecturer/Lecturer

The School of Science and Engineering (SSE) at The Chinese University of Hong Kong, Shenzhen (CUHK-Shenzhen) sincerely invites applications for mul...

Shenzhen, China

The Chinese University of Hong Kong, Shenzhen (CUHK Shenzhen)

Faculty Positions& Postdoctoral Research Fellow, School of Optical and Electronic Information, HUST

Job Opportunities: Leading talents, young talents, overseas outstanding young scholars, postdoctoral researchers.

Wuhan, Hubei, China

School of Optical and Electronic Information, Huazhong University of Science and Technology

Postdoctoral Fellowships at West China Hospital/West China School of Medicine of Sichuan University

Open to PhD students, PhD, Post-Doc and residents.

Chengdu, Sichuan, China

West China School of Medicine/West China Hospital

Welcome Global Talents to West China Hospital/West China School of Medicine of Sichuan University

Top Talents; Leading Talents; Excellent Overseas Young Talents on National level; Overseas Young Talents

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

UCI Anti-Cancer Challenge awards $1 million for promising cancer research

Media contacts.

Matt Miller Director, Communications and Public Relations [email protected]

Michelle Strombeck Manager, Communications and Public Relations 312-498-8208 [email protected]

• River City Live
• Newsletters

WEATHER ALERT

A river flood warning in effect for Columbia County

Cancer patients often do better with less intensive treatment, new research finds.

Carla K. Johnson

Associated Press

Scaling back treatment for three kinds of cancer can make life easier for patients without compromising outcomes, doctors reported at the world’s largest cancer conference.

It’s part of a long-term trend toward studying whether doing less — less surgery , less chemotherapy or less radiation — can help patients live longer and feel better. The latest studies involved ovarian and esophageal cancer and Hodgkin lymphoma.

Recommended Videos

Thirty years ago, cancer research was about doing more, not less. In one sobering example, women with advanced breast cancer were pushed to the brink of death with massive doses of chemotherapy and bone marrow transplants. The approach didn’t work any better than chemotherapy and patients suffered.

Now, in a quest to optimize cancer care, researchers are asking: “Do we need all that treatment that we have used in the past?”

It’s a question, “that should be asked over and over again,” said Dr. Tatjana Kolevska, medical director for the Kaiser Permanente National Cancer Excellence Program, who was not involved in the new research.

Often, doing less works because of improved drugs.

“The good news is that cancer treatment is not only becoming more effective, it’s becoming easier to tolerate and associated with less short-term and long-term complications,” said Dr. William G. Nelson of Johns Hopkins School of Medicine, who was also not involved in the new research.

Studies demonstrating the trend were discussed over the weekend at an American Society of Clinical Oncology conference in Chicago. Here are the highlights:

OVARIAN CANCER

French researchers found that it’s safe to avoid removing lymph nodes that appear healthy during surgery for advanced ovarian cancer. The study compared the results for 379 patients — half had their lymph nodes removed and half did not. After nine years, there was no difference in how long the patients lived and those with less-extreme surgery had fewer complications, such as the need for blood transfusions. The research was funded by the National Institute of Cancer in France.

ESOPHAGEAL CANCER

This German study looked at 438 people with a type of cancer of the esophagus that can be treated with surgery. Half received a common treatment plan that included chemotherapy and surgery on the esophagus, the tube that carries food from the throat to the stomach. Half got another approach that includes radiation too. Both techniques are considered standard. Which one patients get can depend on where they get treatment.

After three years, 57% of those who got chemo and surgery were alive, compared to 51% of those who got chemo, surgery and radiation. The German Research Foundation funded the study.

HODGKIN LYMPHOMA

A comparison of two chemotherapy regimens for advanced Hodgkin lymphoma found the less intensive treatment was more effective for the blood cancer and caused fewer side effects.

After four years, the less harsh chemo kept the disease in check in 94% of people, compared to 91% of those who had the more intense treatment. The trial included 1,482 people in nine countries — Germany, Austria, Switzerland, the Netherlands, Denmark, Sweden, Norway, Australia and New Zealand — and was funded by Takeda Oncology, the maker of one of the drugs used in the gentler chemo that was studied.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

Copyright 2024 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed without permission.

Click here to take a moment and familiarize yourself with our Community Guidelines.

Cookies on the NHS England website

We’ve put some small files called cookies on your device to make our site work.

We’d also like to use analytics cookies. These send information about how our site is used to a service called Google Analytics. We use this information to improve our site.

Let us know if this is OK. We’ll use a cookie to save your choice. You can  read more about our cookies before you choose.

Change my preferences I'm OK with analytics cookies

Thousands of NHS patients to access trials of personalised cancer ‘vaccines’

Thousands of cancer patients in England are set to gain fast-tracked access to trials of personalised cancer vaccines following the launch of a world-leading NHS trial “matchmaking” service to help find new life-saving treatments.

The NHS today announced it has treated its first patient in England with a personalised vaccine against their bowel cancer, in a clinical trial part of NHS England’s new Cancer Vaccine Launch Pad .

In a national first, father-of-four Elliot Phebve received the developmental jab at University Hospitals Birmingham NHS Foundation Trust, one of several sites taking part in the colorectal cancer vaccine trial sponsored by BioNTech SE.

The German biotechnology company will tomorrow (1 June) present new preliminary data at the American Society of Clinical Oncology’s annual conference in Chicago on how measuring circulating tumour DNA could potentially help early detection of colorectal cancer.

The vaccine trial involving Elliot is one of several that will be taking place in NHS trusts across the country to treat different types of cancer. Thousands more patients are expected to benefit from NHS England’s new Cancer Vaccine Launch Pad, which will enable those wanting to participate in clinical trials to be fast-tracked to one of the nearest participating hospitals.

Patients who agree to take part have a sample of their cancer tissue and a blood test taken. If they meet a clinical trial’s eligibility criteria, they can be referred to their nearest participating NHS site, meaning patients from hospitals across the country will find it easier than ever to take part in groundbreaking research.

The investigational cancer vaccines evaluated in the colorectal cancer trial are based on mRNA – the same technology used for the Pfizer-BioNTech COVID-19 vaccine – and are created by analysing a patient’s tumour to identify mutations specific to their own cancer. Using this information, medics then create an experimental individualised cancer vaccine.

The developmental vaccines are designed to induce an immune response that may prevent cancer from returning after surgery on the primary tumour, by stimulating the patient’s immune system to specifically recognise and potentially destroy any remaining cancer cells.

The investigational cancer vaccines being jointly developed by biopharmaceutical companies BioNTech and Genentech, a member of the Roche Group, are still undergoing trials and have not yet been approved by regulators.

Higher-education lecturer Elliot, 55, had no cancer symptoms and was diagnosed through a routine health check with his GP.

Following blood tests, he was immediately invited to Manor Hospital in Walsall and triaged to a hospital ward to receive blood transfusions.

A computed tomography (CT) scan and a colonoscopy confirmed he had colon cancer and Eliott had surgery to remove the tumour and 30 cm of his large intestine. He was then referred to the Queen Elizabeth Hospital Birmingham for initial rounds of chemotherapy and to take part in a clinical trial.

Eliott said : “Taking part in this trial tallies with my profession as a lecturer, and as a community-centred person. I want to impact other people’s lives positively and help them realise their potential.

“Through the potential of this trial, if it is successful, it may help thousands, if not millions of people, so they can have hope, and may not experience all I have gone through. I hope this will help other people.”

Thirty hospitals in England are already signed up to the pioneering Cancer Vaccine Launch Pad – one of the biggest projects of its kind in the world – with more sites joining the platform over the coming months.

The scheme aims to expand and work with a range of partners in the pharmaceutical industry to include patients across many cancer types who could potentially join a vaccine trial, such as those with pancreatic and lung cancer.

Amanda Pritchard, NHS chief executive, said : “Seeing Elliot receive his first treatment as part of the Cancer Vaccine Launch Pad is a landmark moment for patients and the health service as we seek to develop better and more effective ways to stop this disease.

“Thanks to advances in care and treatment, cancer survival is at an all-time high in this country, but these vaccine trials could one day offer us a way of vaccinating people against their own cancer to help save more lives.

“The NHS is in a unique position to deliver this kind of world-leading research at size and scale, and as more of these trials get up and running at hospitals across the country, our national match-making service will ensure as many eligible patients as possible get the opportunity to access them.”

Trials have already enlisted dozens of patients, although the majority of participants are expected to be enrolled from 2026 onwards.

Professor Peter Johnson, NHS national clinical director for cancer at the NHS said : “We know that even after a successful operation, cancers can sometimes return because a few cancer cells are left in the body, but using a vaccine to target those remaining cells may be a way to stop this happening.

“Access to clinical trials could provide another option for patients and their families, and I’m delighted that through our national launch pad we will be widening the opportunities to be part of these trials for many more people, with thousands of patients expected to be recruited in the next year.”

Principal Investigator for the trial at Queen Elizabeth Hospital Birmingham, Consultant Clinical Oncologist, Dr Victoria Kunene, said:  “The investigational cancer vaccines are based on mRNA and are created by analysing a patient’s tumour to identify mutations specific to their own cancer. Using this information, we can create an individualised investigational cancer vaccine, but it is too early yet to say if these will be successful, though we are extremely hopeful. Based on the limited data we currently have of the in-body response to the vaccine, this could prove to be a significant and positive development for patients, but more data is yet needed and we continue to recruit suitable patients to the trial to establish this further.”

Executive Director of Research and Innovation at Cancer Research UK, Iain Foulkes, said: “It’s incredibly exciting that patients in England are beginning to access personalised cancer vaccines for bowel cancer.

“This technology pioneers the use of mRNA-based vaccines to sensitise people’s immune system and in turn detect and target cancer at its earliest stages. Clinical trials like this are vital in helping more people live longer, better lives, free from the fear of cancer. If successful, the vaccine will be a game changer in preventing the onset or return of bowel cancer.”

Last year, the Government signed an agreement with BioNTech to provide up to 10,000 patients with precision cancer immunotherapies by 2030.

BioNTech has already begun conducting clinical trials in the UK, and the NHS launch pad is helping to accelerate the identification of eligible patients for those trials in England.

The vaccines being tested as part of the trials aim to help patients with different types of cancer and, if successfully developed, researched and approved, cancer vaccines could become part of standard care.

The NHS is working in partnership with Genomics England on the launch pad, with work already helping patients access the latest testing technologies and ensures they are given more targeted precision treatments for their cancer.