Adherence to vaccination schedules in patients under active oncological treatment and follow-up: protocol for a systematic review and meta-analysis

Abstract

Introduction

Vaccination is a key public health strategy for preventing infectious diseases and is particularly relevant for patients with cancer because of disease-related and treatment-related immunosuppression. Optimising vaccination status should be considered a fundamental component of care for this population; however, in clinical practice, vaccination may be neglected during active treatment and survivorship follow-up.

Methods and analysis

This systematic review and meta-analysis protocol will include observational studies (cross-sectional, case-control and cohort studies) evaluating adherence to age-based and seasonality-based vaccination schedules among adults with cancer who are undergoing active oncological treatment or post-treatment follow-up. Eligible vaccines include COVID-19, influenza, invasive pneumococcal disease, tetanus/diphtheria/pertussis, herpes zoster, human papillomavirus and hepatitis B vaccines. Searches will be conducted in PubMed/MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, ScienceDirect, CINAHL and LILACS without restrictions on language or publication date. Study selection and data extraction will be performed independently by two reviewers, with disagreements resolved by discussion or by a third reviewer. Risk of bias will be assessed using the Joanna Briggs Institute tool for cross-sectional studies and the Newcastle-Ottawa Scale for cohort and case-control studies. The certainty of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. When appropriate, random-effects meta-analysis will be performed using RevMan V.5.2.3; otherwise, findings will be synthesised narratively. The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) reporting guidance. Article selection and data collection will be carried out from October 2026 to January 2027.

Ethics and dissemination

Ethical review is not required because this study will use only publicly available published literature. The findings will be disseminated through publication in a peer-reviewed journal and scientific presentations.

Prospero registration number

CRD420261295899.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This protocol addresses vaccination adherence across both active oncological treatment and post-treatment follow-up, allowing comparison between phases of cancer care.

• The review will consider multiple vaccines, including age-based and seasonal vaccines, to provide a broad overview of adherence and coverage in adult oncology populations.

• A comprehensive search strategy will be applied across major international and regional databases without language or date restrictions.

• Independent study selection, data extraction, and risk-of-bias assessment will reduce selection and extraction errors.

• Potential heterogeneity in cancer types, treatment regimens, vaccine schedules and definitions of adherence may limit quantitative pooling and may require narrative synthesis.

Introduction

Vaccines remain among the most important public health strategies for the prevention of infectious diseases and are particularly relevant for patients with cancer. Population-based studies have demonstrated low adherence to recommended vaccination schedules among individuals with cancer.^1–3

Studies evaluating the administration of vaccines among patients diagnosed with cancer, including those against COVID-19, influenza, invasive pneumococcal disease, tetanus/diphtheria/pertussis, herpes zoster, human papillomavirus and hepatitis B, have shown substantial gaps in adherence. Complete adherence to all recommended vaccinations has been reported in only a small proportion of patients.² In addition, cancer patients remain under-vaccinated against influenza and pneumococcal disease, two vaccine-preventable infections associated with important morbidity in this population.⁴

Adherence to vaccination schedules is widely recognised as a challenge among cancer survivors, often because healthcare professionals and patients prioritise cancer treatment while preventive care, including vaccination, is marginalised or forgotten.^{3 4}

Vaccine hesitancy may also contribute to low adherence. Chan et al reported that many patients with cancer expressed concerns that vaccination might adversely affect their cancer treatment, reflecting anxiety about interactions between vaccination and oncological care. Some patients also reported being advised to postpone vaccination after systemic therapy during early phases of the COVID-19 vaccine rollout, when safety data for cancer populations were limited.⁴

In this context, this review aims to evaluate adherence to recommended vaccination schedules according to age and seasonality among adult patients with cancer, including those undergoing active oncological treatment and those in post-treatment follow-up, and to identify factors influencing vaccination decision-making.

Objectives

Primary objective

To evaluate adherence to recommended vaccination schedules among adult patients with cancer undergoing active oncological treatment and those in post-treatment follow-up, including age-based vaccines and seasonal vaccines such as influenza and COVID-19 vaccines.

Secondary objectives

• To determine vaccination coverage rates by vaccine type and treatment status.

• To identify barriers and facilitators to vaccination adherence.

• To analyse factors associated with vaccine acceptance or refusal in both treatment phases.

Methods and analysis

This systematic review and meta-analysis protocol was prepared in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement.⁵ Observational studies will be identified through systematic searches conducted from database inception to February 2026. No restrictions regarding language or publication date will be applied. The population of interest will be adult patients diagnosed with cancer who are undergoing active oncological treatment, including chemotherapy, immunotherapy, targeted therapy, radiotherapy or hormonal therapy, or who are in post-treatment follow-up.

Study selection and data extraction will be carried out independently by two reviewers using predefined criteria and standardised forms. Risk of bias will be evaluated using the Joanna Briggs Institute standardised critical appraisal tool for cross-sectional studies⁶ and the Newcastle-Ottawa Scale for cohort and case-control studies.⁷ The certainty of evidence will be assessed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.⁸

Data synthesis will be performed using Review Manager (RevMan) V.5.2.3. Statistical heterogeneity across studies will be examined using the I² statistic. When the included studies demonstrate sufficient methodological and clinical homogeneity, quantitative synthesis will be undertaken using a random-effects model. When meta-analysis is not feasible, results will be synthesised narratively.

Inclusion criteria

Observational studies (cross-sectional, case-control and cohort studies) evaluating adherence to age-based and seasonality-based vaccination schedules among adult patients with cancer will be included. Eligible patients may be undergoing active oncological treatment or post-treatment follow-up. Eligible vaccines include COVID-19, influenza, invasive pneumococcal disease, tetanus/diphtheria/pertussis, herpes zoster, human papillomavirus and hepatitis B vaccines.

Exclusion criteria

Clinical trials, review articles, reports, case series, conference abstracts without peer review and non-peer-reviewed publications will be excluded. Studies involving paediatric populations will also be excluded.

Population, outcome and study type

• Population: adult patients diagnosed with cancer who are either undergoing active oncological treatment or are in post-treatment follow-up.

• Outcome: adherence to vaccination schedules for COVID-19, influenza, invasive pneumococcal disease, tetanus/diphtheria/pertussis, herpes zoster, human papillomavirus and hepatitis B vaccines.

• Types of study: observational studies, including cross-sectional, case-control and cohort studies.

Patient and public involvement

Patients and members of the public were not involved in the design, conduct, reporting or dissemination plans of this systematic review protocol.

Search strategies

The following databases will be searched: PubMed/MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, ScienceDirect, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). There will be no language or date restrictions.

The search strategy will be structured around key conceptual blocks. Terms related to cancer diagnosis and treatment phase will be combined with terms related to vaccination and immunisation, vaccination adherence or coverage, and observational study designs. These concepts will be combined using Boolean operators. The complete MEDLINE strategy is presented in table 1. Full search strategies adapted for all remaining databases are provided in online supplemental table S1 (Search_Strategy).

Table 1. MEDLINE (via PubMed) search strategy.

Step	Concept	Search terms
1	Cancer	neoplasms[MeSH Terms] OR cancer*[tiab] OR neoplasm*[tiab] OR oncology[tiab] OR oncologic*[tiab] OR tumor*[tiab] OR tumour*[tiab] OR malignan*[tiab]
2	Treatment phase and survivorship	chemotherapy[tiab] OR immunotherapy[tiab] OR radiotherapy[tiab] OR radiation therapy[tiab] OR targeted therapy[tiab] OR hormonal therapy[tiab] OR active treatment[tiab] OR cancer survivor*[tiab] OR survivorship[tiab] OR follow-up care[tiab]
3	Vaccination	vaccination[MeSH Terms] OR immunization[MeSH Terms] OR vaccine*[tiab] OR vaccination[tiab] OR immunisation[tiab] OR immunization[tiab] OR influenza vaccine[tiab] OR COVID-19 vaccine[tiab] OR pneumococcal vaccine[tiab] OR herpes zoster vaccine[tiab] OR HPV vaccine[tiab] OR hepatitis B vaccine[tiab]
4	Adherence and coverage	adherence[tiab] OR uptake[tiab] OR coverage[tiab] OR acceptance[tiab] OR refusal[tiab] OR hesitancy[tiab] OR compliance[tiab] OR completion[tiab]
5	Observational design	observational stud*[tiab] OR cross-sectional[tiab] OR cohort[tiab] OR case-control[tiab] OR longitudinal[tiab] OR follow-up stud*[tiab]
6	Final combination	#1 AND #2 AND #3 AND #4 AND #5

Study selection

Following the database search, all retrieved articles will be imported into a reference management system (Rayyan.ai) and duplicates will be removed. Study selection will be performed independently by two researchers (GOM and AGXN) based on titles and abstracts. Discrepancies between reviewers will be resolved through discussion and, if necessary, by consulting a third researcher (MLA). Full-text articles of potentially eligible studies will then be assessed for inclusion according to predefined eligibility criteria. The study selection process, including reasons for exclusion at each stage, will be documented and presented using a PRISMA flow diagram (figure 1).

Figure 1. Preferred Reporting Items for Systematic Review and Meta-Analysis flow diagram.

Data extraction

Data extraction will be performed independently by two researchers using a standardised electronic form. Extracted data will include authors, year of publication, country and study site, study design, study objectives, mean or median age of participants, cancer type, oncological treatment status (active treatment vs surveillance/follow-up), vaccination schedules, follow-up period, adherence rates according to age group and seasonality, vaccination coverage rates by vaccine type, barriers and facilitators to adherence, and factors associated with vaccine acceptance or refusal. Article selection and data collection will be carried out from October 2026 to January 2027.

Data synthesis

Data analysis will be conducted using Review Manager (RevMan) V.5.2.3. Given the anticipated variability among included studies, a random-effects model will be used for meta-analysis when appropriate. Effect sizes for dichotomous outcomes will be expressed as risk ratios, ORs or prevalence ratios, while continuous outcomes will be summarised using weighted or standardised mean differences, with corresponding 95% CIs. For cohort studies, results will be reported as risk ratios or prevalence ratios with 95% CIs, whereas case-control studies will present ORs with 95% CIs.

Statistical heterogeneity will be evaluated using the I² statistic. If meta-analysis is not feasible or if substantial heterogeneity is observed, findings will be synthesised narratively. Sensitivity analyses will be performed to assess the influence of study quality on the results. Publication bias will be evaluated for outcomes including more than 10 studies using funnel plots, with Egger’s test applied to continuous outcomes to assess potential asymmetry.

Quality assessment

The methodological quality of the studies included in this review will be independently evaluated by two reviewers. For cross-sectional studies, critical appraisal will be performed using the Joanna Briggs Institute standardised assessment tool appropriate for this study design.⁶ For cohort and case-control studies, risk of bias will be independently assessed using the Newcastle-Ottawa Scale.⁷ Disagreements between reviewers will be resolved through discussion and, when necessary, by consultation with a third reviewer. Study authors will be contacted when additional clarification is required to ensure an accurate assessment of risk of bias.

Assessing certainty in the findings

The certainty of the evidence will be assessed using the GRADE approach.⁸ Two authors will independently perform this assessment, and disagreements will be resolved through discussion with a third author. The GRADE framework categorises evidence according to risk of bias, indirectness, inconsistency, imprecision and publication bias.

Ethics and dissemination

Ethical review is not required because this systematic review will use only publicly available published literature and will not involve individual participant data. For research integrity or ethics-related queries, the Research Support Center of Hospital Sírio-Libanês can be contacted at apoioaopesquisador@hsl.org.br addressed to DAS. The findings of this systematic review will be disseminated through publication in a peer-reviewed journal and scientific presentations.

Discussion

Although vaccination is a priority for patients with cancer, achieving high coverage remains challenging. Sabatino et al reported low adherence to recommended adult vaccination schedules among individuals with cancer.¹ Other observational data have shown incomplete adherence to routine vaccination schedules among oncology patients and gaps across multiple vaccines.^2–4

Among vaccine-preventable infections that pose a risk to patients with cancer, influenza and pneumococcal disease are especially important. Current guidance emphasises the need to optimise vaccination in adults with cancer and other immunocompromised populations.^9–11 Inactivated vaccines are generally considered safe in immunocompromised patients, although the immune response may be attenuated depending on the malignancy, treatment type and degree of immunosuppression. Live attenuated vaccines are generally contraindicated during periods of significant immunosuppression.^{9 10}

Revaccination or additional doses after periods of medication-induced immunosuppression may need to be considered on an individualised basis.⁹ Vaccine uptake may also be affected by socioeconomic factors, racial disparities, health-system access and care fragmentation, all of which can influence preventive care among cancer survivors.¹²

Several quantitative studies have described hesitancy and underuse of vaccination among patients with cancer, particularly among those undergoing chemotherapy. Qualitative evidence also suggests that barriers and facilitators to vaccination include perceived safety, clinician recommendation, access to vaccination services, knowledge gaps and competing priorities during cancer care.¹³

A recent systematic review by Lo Moro et al focused on interventions and strategies aimed at increasing vaccination uptake among adult cancer patients.¹⁴ In contrast, the present review is designed to quantify adherence to recommended vaccination schedules among adults with cancer undergoing active treatment or follow-up care, estimate vaccination coverage across different vaccine types, and identify barriers, facilitators and factors associated with vaccine acceptance or refusal. This review therefore addresses a broader epidemiological question and may provide quantitative estimates of vaccination adherence across different oncological settings.

This protocol was designed to systematically identify and synthesise evidence regarding vaccination adherence among adult patients with cancer, including those undergoing active treatment and those in follow-up care, and to explore barriers and facilitators influencing adherence across different phases of oncological care.

Systematic reviews of observational studies are mainly limited by substantial heterogeneity, which often cannot be fully explored due to incomplete subgroup reporting in primary studies. Furthermore, potential biases within the primary studies themselves present an additional limitation.