BACKGROUND: Infections are one of the most frequent complications seen in adults with cancer, often arising from the underlying condition or as a result of immunosuppressive treatments. Certain infections (e.g. influenza, pneumococcal disease, and meningococcal disease) may be prevented through vaccination. However, adults with solid tumours may elicit varying immune responses compared to healthy individuals.
OBJECTIVES: To assess the benefits and risks of vaccines for the prevention of infectious diseases in adults with solid tumours.
SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, two further databases, and two study registries from inception to 2 December 2024 for randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs).
SELECTION CRITERIA: We included RCTs evaluating vaccines against the following infectious diseases in adults (≥ 18 years of age) with any diagnosis of solid tumour cancer compared to placebo or no vaccine: pneumococcal disease, Haemophilus influenzae type b disease, meningococcal disease, pertussis, hepatitis B, tetanus, polio, diphtheria, influenza, herpes zoster, and COVID-19. In cases where RCTs were unavailable, we included prospective controlled NRSIs. We excluded live-attenuated vaccines.
DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. Two review authors independently screened search results, extracted data, and assessed the risk of bias (RoB) in the included studies using the Cochrane RoB 2 tool for RCTs and ROBINS-I for NRSIs. We rated the certainty in the evidence using the GRADE approach for the following prioritised outcomes: incidence of infection concerned, all-cause mortality, quality of life, adverse events (AEs) of any grade, serious adverse events (SAEs), localised events at the injection site, and systemic events.
MAIN RESULTS: We included 10 studies (five RCTs and five NRSIs) involving 81,823 adults with solid tumours receiving vaccines to prevent infections with herpes zoster, influenza, or COVID-19. Six studies included participants with varied solid tumours, while two focused on neck and oesophageal cancer or lung cancer. We assessed the RCTs to be at low or moderate risk of bias, whereas most NRSIs were at critical risk of bias due to concerns about confounding. We identified two ongoing studies: one RCT evaluating an influenza vaccine, and one NRSI evaluating COVID-19 vaccines. Twelve studies are awaiting assessment. We did not identify RCTs or NRSIs of vaccines for preventing pneumococcal disease, Haemophilus influenzae type b disease, meningococcal disease, pertussis, hepatitis B, tetanus, polio, or diphtheria compared to placebo or no vaccine. The results from the RCTs are presented below. The results from the NRSIs are detailed in the main text of the review. No study reported quality of life. Vaccines for preventing herpes zoster compared to placebo or no vaccine Three RCTs (3054 participants) evaluated vaccines to prevent herpes zoster. Herpes zoster vaccines decrease the incidence of herpes zoster up to 29.4 months after the final dose (RR 0.37, 95% CI 0.23 to 0.59; 1 RCT, 2678 participants; high-certainty evidence). Herpes zoster vaccines probably make little or no difference to all-cause mortality up to 28 days after the final dose (RR 1.17, 95% CI 0.91 to 1.50; 2 RCTs, 2744 participants; moderate-certainty evidence); make little or no difference to any-grade AEs up to 30 days after final dose (RR 1.02, 95% CI 0.98 to 1.05; 3 RCTs, 2976 participants; high-certainty evidence), and probably make little or no difference in SAEs up to 30 days (RR 1.08, 95% CI 0.93 to 1.24; I² = 0%; 3 RCTs, 2976 participants; moderate-certainty evidence). Vaccines to prevent herpes zoster increase the number of participants with localised events at the injection site compared to placebo or no vaccine (RR 6.81, 95% CI 2.52 to 18.40; 3 RCTs, 2966 participants; high-certainty evidence) and may make little or no difference to the number of participants with systemic events up to 30 days after final dose (RR 1.08, 95% CI 0.77 to 1.50; 3 RCTs, 2966 participants; low-certainty evidence). Vaccines for preventing influenza compared to placebo or no vaccine One RCT (75 participants) evaluated vaccines to prevent influenza. We are uncertain about the effects of influenza vaccines administered prior to surgery on all-cause mortality (RR 1.00, 95% CI 0.07 to 15.33; 1 RCT, 66 participants; very low-certainty evidence), any-grade AEs (RR 1.17, 95% CI 0.89 to 1.54; 1 RCT, 75 participants; very low-certainty evidence), and SAEs (RR 1.46, 95% CI 0.76 to 2.83; 1 RCT, 75 participants; very low-certainty evidence) up to 15 days post-surgery. The RCT did not report the incidence of influenza, localised events at the injection site, or systemic events. Vaccines for preventing COVID-19 compared to placebo or no vaccine One RCT (2256 participants) evaluated vaccines to prevent COVID-19. Participants may have been exposed to the SARS-CoV-2 variants alpha, beta, and gamma. Vaccines to prevent COVID-19 probably decrease the incidence of COVID-19 in participants without previous COVID-19 infection up to six months after the second dose (RR 0.08, 95% CI 0.02 to 0.25; 1 RCT, 2100 participants; moderate-certainty evidence). The COVID-19 vaccines probably increase any-grade AEs (RR 1.99, 95% CI 1.71 to 2.30; 1 RCT, 2328 participants; moderate-certainty evidence). They may have little or no effect on SAEs up to 6 months after the second dose (RR 1.43, 95% CI 0.80 to 2.54; 1 RCT, 2328 participants; low-certainty evidence). The RCT did not report localised events at the injection site or systemic events.
AUTHORS' CONCLUSIONS: In adults with solid tumours, herpes zoster vaccines reduced the incidence of herpes zoster (high-certainty evidence), although localised events at the injection site were more likely to occur (high-certainty evidence). The evidence is very uncertain about the effects of influenza vaccines on all-cause mortality, any-grade AEs, and SAEs (very low-certainty evidence); the incidence of influenza was not measured in the studies. COVID-19 vaccines probably decrease the incidence of COVID-19 in those without prior infection (moderate-certainty evidence) but probably increase any-grade AEs (moderate-certainty evidence). We found no RCTs or NRSIs investigating vaccines for preventing pneumococcal disease, Haemophilus influenzae type b disease, meningococcal disease, pertussis, hepatitis B, tetanus, polio, diphtheria compared to placebo or no vaccine, in adults with solid tumours. Additional research, preferably of RCT design, is necessary to resolve uncertainties.
