The substantial changes of human papillomavirus (HPV) type distribution and reductions of cervical precancer and cancer incidence in vaccinated populations, which are entering screening programs now, require reassessment of screening and triage approaches to maintain the balance of benefits and harms of cervical cancer screening. The reduction of precancer and cancer in vaccinated populations affects the risk indicated by most screening and triage tests. Among HPV-positive women, the type distribution changes in vaccinated women to less carcinogenic types that are less likely to progress to precancer, and that cause precancers that are less likely to invade. Conversely, HPV vaccines do not affect the natural history of existing HPV infections. Although infections with vaccine-targeted types are rare in vaccinated populations, their risk of precancer and cancer is not reduced. Host biomarkers that are more closely linked to the carcinogenic process are more likely to perform well in vaccinated individuals compared with biomarkers that mostly reflect HPV infections. We summarize data on HPV screening and triage tests, including cytology, dual stain, and methylation tests, either directly evaluated in vaccinated populations or in HPV genotype strata to estimate their performance in vaccinated populations. Combinations of limited or extended genotyping HPV tests with triage biomarkers can provide meaningful risk stratification for both unvaccinated and vaccinated populations.
As decisions are made worldwide about the best way to adapt cervical screening to cohorts and individuals who have been offered human papillomavirus (HPV) vaccination, we consider the issues this raises for communication. This article reviews the relevant literature on knowledge and awareness of HPV, lessons we can learn from emerging evidence on attitudes to risk-adapted cancer screening, and what the psychological literature tells us about the complex relationships between risk perceptions and behavior. We highlight the need to ensure communication strategies do not create or widen social inequalities. We conclude that there is a strong need for public education about the relationship between HPV, vaccination, screening, and cancer outcomes, an imperative for timely and transparent communication about the rationale for any proposed changes, a need to involve health-care professionals in supporting women to understand the changes, and a strong case for ongoing research and evaluation as changes are implemented.
As vaccination coverage expands, the epidemiology of human papillomavirus (HPV) infection and related disease is shifting. The declining prevalence of infections by the most high-risk HPV types, for example, HPV16 and HPV18, reduces the positive predictive value of screening tests for cervical precancer and cancer and challenges the balance between benefits and harms of current standard-of-care screening intervals. This evolving context raises an important policy question: Can and should cervical cancer screening eventually be reduced or even stopped in fully HPV-vaccinated populations?
Our aspiration is a future with universal administration prior to exposure using simply delivered and affordable vaccines covering all high-risk human papillomavirus (HPV) types and other HPVs associated with significant morbidity. However, this scenario remains unrealized: no vaccine today covers the full range of high-risk HPV types, nor have we reached every population that needs HPV vaccination, so infection remains prevalent. The reasons are multifaceted, involving scientific, economic, sociocultural, and logistical hurdles, yet efforts are ongoing worldwide to overcome these challenges. Broad implementation of primary HPV-based screening, including self-sampling, will improve cervical cancer prevention and inform many more women of their high-risk HPV-positive status. Development of high-risk HPV-targeted therapeutics could further accelerate declines in cervical cancer by clearing prevalent infections. Progress on HPV vaccination and improvements in screening technology continue at a remarkable pace. Reduction in cervical cancer incidence is evident where vaccination and/or screening have been adopted early and widely implemented.
Cervical cancer remains a public health problem, with the highest burden in low- and middle-income countries (LMICs). As vaccinated cohorts reach screening age, most modeling and policy discussions about the relationship between screening and vaccination have focused on high-income countries, early adopters of human papillomavirus (HPV) vaccination with robust, well-established cervical cancer screening programs. Challenges and solutions proposed for these settings are not necessarily applicable to LMICs, which have historically lagged in cancer prevention and operate within more constrained health systems. We analyze HPV vaccination patterns by country-level income and highlight inequities across program rollout and coverage. Using 6 LMICs expected to screen vaccinated cohorts before 2030, we outline financial, health-system, and information-system challenges. We examine how mathematical models may guide screening policies and illustrate, through Costa Rica's experience, how research can support implementation of cervical cancer elimination interventions. LMICs will need cost-effective risk-stratified screening approaches tailored to local resources as cervical cancer risk declines over coming years. However, because many women more than 30 years old have not been vaccinated and remain at risk of developing cervical cancer, global efforts to ensure good-quality screening are crucial.
Screening recommendations in the United States have not been modified for women who have been vaccinated against human papillomavirus (HPV). Using 3 independent Cancer Intervention and Surveillance Modeling Network (CISNET) models (Policy1-Cervix, Harvard and STDSIM-MISCAN), we evaluated the impact of switching from 3-yearly cytology-based screening for ages 21-65 ("cytology alone") to primary-HPV-16/18 screening for ages 25-65 every 5-years ("standardized 5-yearly HPV screening"), or every 8-10 years for younger vaccinated cohorts ("tailored HPV screening"). Compared to cytology alone, switching to standardized 5-yearly HPV screening for all women would reduce total cervical cancer deaths over the period 2020-2099 by 9%-14% and total colposcopies by 15%-49%, and achieve cervical cancer elimination by 2030-2037, 4 years earlier than cytology screening alone. Compared to cytology alone, tailored HPV screening would reduce cervical cancer deaths over the period 2020-2099 by 2%-14%, colposcopies by 30%-59%, and achieve elimination by 2030-2040, 1-4-years earlier. In conclusion, primary HPV screening in all women would be associated with improved health outcomes and would reduce colposcopy referrals in the longer term compared to older, cytology approaches. Tailoring the HPV screening interval to vaccination status has potential to increase efficiencies and maintain effectiveness and elimination timing.
There is substantial evidence examining effectiveness of human papillomavirus vaccines in populations using registry linkages. These studies initially mapped early outcomes, but in recent years have focused on harder endpoints, confirming that the vaccines have the anticipated effect against infection, lesions, and ultimately invasive cervical cancer. It is generally accepted that when vaccinated cohorts enter screening programs, adjustments to screening strategies are needed to maintain the balance of benefits and harms and achieve optimal resource use. The purpose of this chapter is to examine the practical considerations for implementing tailored screening in the context of increasingly vaccinated populations, with particular emphasis on data sources and their application in routine practice. We present real-world examples of linking vaccination and screening registries to enable screening strategies informed by individual human papillomavirus vaccination status. We also outline the common challenges encountered when establishing such linkages and offer practical suggestions for overcoming them.
The success of prophylactic human papillomavirus (HPV) vaccination in reducing disease burden came with an epidemiological concern: HPV type replacement, the potential compensatory increase of nonvaccine targeted HPV types following the elimination of HPV16 and 18. Postvaccination surveillance across several countries suggests some signs of increase in the nonvaccine targeted HPV types, which may be explainable because of type replacement. However, should HPV type replacement be occurring, it is unlikely to generate disease replacement because of the significantly lower oncogenic potential of nonvaccine targeted HPV types. The modernization of screening to align with this new risk profile is necessary. Personalized screening protocols based on individual risk profiles informed by primary HPV testing with extended genotyping and future molecular triage to accurately risk-stratify HPV types are necessary in the postvaccination era.
Screening has been instrumental in reducing the global burden of cervical cancer over the past several decades. However, the landscape of prevention and early detection is rapidly evolving, driven by widespread human papillomavirus (HPV) vaccination, advances in molecular diagnostics, and a growing emphasis on personalized medicine, which collectively call for a reassessment of traditional screening paradigms to align with the new risk landscape. In settings with a high prevalence of cervical precancerous lesions, where cytology and HPV testing yield a substantial proportion of true positives, frequent screening intervals are justified. Conversely, in vaccinated populations where the incidence of precancerous lesions is becoming substantially reduced, screening, irrespective of test modality, produces more false positives, leading to unnecessary diagnostic procedures and their consequent reproductive health risks and psychological distress. In HPV-based screening, reduced positive predictive value (PPV) in vaccinated populations reflects the lower oncogenic potential of nonvaccine HPV types that predominate postvaccination. Although these infections are detectable, they are less likely to progress to high-grade precancer or cancer, thereby lowering PPVs. In cytology-based screening, PPV declines for 2 reasons. First, as vaccine-targeted high-risk infections are eliminated, lower-risk infections account for a greater share of cytologic abnormalities. Second, as true precancerous lesions decline, nonspecific cytologic abnormalities, unrelated to HPV, become more prominent, increasing false positives and further reducing PPV. This commentary, drawing on prior work from our group, examines the complex interplay among disease prevalence, individual risk profiles, test performance, and screening program design and argues for a transition toward risk-based screening strategies that reflect changing epidemiological patterns and align with contemporary public health priorities. It further argues for adaptive, evidence-informed policies that incorporate molecular tools such as HPV genotyping and methylation assays to optimize prevention and early detection in the postvaccination era.
Population-wide human papillomavirus vaccination has transformed the epidemiology of cervical cancer and accelerated the interest in risk-adapted screening approaches that tailor screening intervals, methods, and triage pathways to an individual's vaccination status and underlying risk. Although modeling studies suggest that vaccinated cohorts may require fewer lifetime screenings and later screening initiation, implementation science provides frameworks, methods, and strategies to guide the translation of these approaches into practice. However, real-world implementation is complex and constrained by incomplete linkages with immunization records, evolving evidence on cross-protection, and persistent inequities in screening participation. By focusing on multilevel contextual determinants that span patients, clinicians, organizations, and policy environments, implementation science can guide the design, testing, and optimization of strategies such as clinical decision support tools, tailored communication, and clinical workflow redesign that are required to translate emerging evidence into practice. We highlight examples from pragmatic and hybrid effectiveness-implementation trials demonstrating how approaches such as self-sampling, participatory co-design, peer advocacy models, and multicomponent strategies improve screening reach, acceptability, and fidelity. As risk-adapted screening becomes the next frontier in cervical cancer prevention, embedding implementation science early can prevent future translational bottlenecks, support equity, and ensure that health systems are prepared to adopt and sustain evidence-based recommendations once epidemiological data mature while guiding a research agenda for implementation of risk-adapted screening worldwide.
Exercise is recommended as a part of standard cancer care, based upon its favorable impact on treatment-related side effects and its association with better cancer outcomes. Fully incorporating exercise into oncology practice will require multidisciplinary efforts across oncology and exercise professionals. This article examines current patterns of exercise advice and prescription in oncology settings and highlights the roles of oncology clinicians, physiatrists, physical and occupational therapists, exercise physiologists and fitness trainers, and patient advocates in expanding exercise oncology across the cancer continuum. Future efforts to enhance provider education, expand community-based programs, establish referral pathways, and address policy challenges related to reimbursement will be needed to establish exercise as a universally accessible and effective component of oncology care.
Exercise is increasingly recognized by patients, clinicians, and allied health professionals globally as an important component of cancer care. In this paper, we provide a viewpoint on developments in exercise oncology over the past 4 decades leading up to the creation of the International Society of Exercise Oncology (ISEO). We briefly review research in adult and pediatric cancers from early foundation studies to larger randomized controlled trials published in mainstream oncology journals alongside critical work undertaken in exercise and cancer biological mechanisms. We also discuss potential strengths, weaknesses, opportunities, and threats facing ISEO in becoming a global forum for exercise oncology. Building on the foundational work undertaken over the past 4 decades by researchers, clinicians, and practitioners, ISEO provides an opportunity to support research, leverage collaborations and partnerships, facilitate education and training, increase awareness of exercise oncology, and support translation of research to clinical practice, ultimately improving the quality and quantity of life for people with cancer.
Exercise oncology is a multidisciplinary field that encompasses research across the translational continuum. Some of the major disciplines contributing to the field include biology, immunology, physiology, psychology, behavioral science, epidemiology, and clinical oncology. Here, we provide a brief overview of the field under the headings of preclinical studies, observational studies, interventional outcome studies, interventional behavioral studies, dissemination and implementation studies, and childhood cancer studies. Preclinical studies have generally demonstrated that exercise can reduce tumor growth, primarily by modulating the tumor microenvironment. Observational studies have generally demonstrated that higher postdiagnosis exercise is associated with lower rates of mortality, however, most studies have not considered the combination and sequencing of exercise with other cancer treatments. Interventional outcome studies have consistently demonstrated strong evidence that aerobic and/or resistance exercise have beneficial effects on fatigue, anxiety, depression, physical functioning, and quality of life in adult patients treated with curative intent. Childhood cancer studies have demonstrated beneficial effects on cardiorespiratory fitness and muscular strength; however, the quality of evidence is often low. Interventional behavioral studies have identified multiple effective exercise behavior change strategies, yet the evidence is limited by a lack of diversity, minimal attention to social determinants, and insufficient knowledge to tailor interventions. Dissemination and implementation studies are occurring globally, yet an evidence base identifying the most cost-effective, equitable, and sustainable strategies is limited. Notwithstanding substantial limitations and remaining research gaps, multidisciplinary exercise oncology research across the translational continuum has provided cancer patients with evidence-based recommendations for improving quality of life and possibly survival.
Exercise oncology has emerged as a distinctive area of research and clinical practice. To obtain a global overview of this field, we summarize viewpoints from experts across 6 continents on (1) the scope of exercise oncology research and programs, (2) the availability of reimbursement for cancer exercise services, and (3) pathways and initiatives for developing the exercise oncology workforce. From an international perspective, the field of exercise oncology has progressed substantially; however, gains made to date are uneven, with general underdevelopment in Africa, Asia, and South and Central America. In addition, the availability of cancer exercise services continues to fall short of the increasing demand worldwide. With the upcoming formation of the International Society of Exercise Oncology, we suggest leveraging coordinated efforts from the global exercise oncology community to optimize research capacity, enhance workforce development, and expand the delivery of exercise services to advance the field across the world.
This commentary demonstrates the value of exercise for individuals living with breast cancer from the patient perspective. Exercise helps patients feel better while they undergo cancer treatment and beyond. Clinicians are urged to consider inclusion of exercise as standard of care during and after cancer treatment.
Exercise oncology is coming of age, with more than 30 000 peer-reviewed citations in the scientific literature and multiple guidelines published by major medical institutions based on strong evidence from randomized controlled trials. There is enthusiasm around the formation of a new international organization that will form a nexus for exercise oncology researchers, clinicians, and practitioners. The contents of this monograph document the progression of exercise oncology research and practice, laying the groundwork for the formation of the International Society of Exercise Oncology. The society will aim to be an organizing body to shepherd the field toward the goal of using exercise as standard of care in the setting of oncology in collaboration with existing medical organizations so that every patient can benefit.
Exercise is safe and beneficial for people diagnosed with cancer. The use of live-remote exercise approaches, where exercise trainers deliver exercise programs via a videoconferencing platform, has increased rapidly, greatly expanding the reach of exercise programs. This method retains key elements of supervised exercise, which provide greater benefits than unsupervised programs. However, challenges in adapting in-person supervised exercise programs to remote delivery exist. This article discusses the key considerations for the effective and safe delivery of live-remote exercise, such as technological requirements, exercise professional skills, safety aspects, exercise programming features, social interactions, costs, and legal and ethical considerations. Considerations relevant for the design and execution of exercise oncology clinical trials and for community practice are described. Remaining knowledge gaps are outlined and point to opportunities to further inform evidence-based practice and practice-based evidence.
The complex requirements of people with cancer can impact the provision of safe, effective, evidence-based exercise prescription. Consequently, a range of essential competencies are required from the exercise oncology workforce. There is a global need for a standardized approach to the development of this workforce. By defining, standardizing, and training the workforce in essential competencies, this will enable various professionals to safely and effectively screen, access, design, and deliver appropriate exercise programs. Therefore, this is also a call for a global collaboration on the development of the exercise oncology workforce with special attention to assisting low- or middle-income countries with their increasing cancer burden and unique challenges, which may require unique context-specific strategies. The building of an appropriate internationally standardized workforce is essential in the provision of physical activity and exercise options as part of standard cancer care.
