ImportanceHead and neck cancers (HNCs) are often diagnosed at advanced clinical stages during their symptomatic phase, leading to a reduced treatment window and poor survival. Screening programs have been suggested as a mitigation strategy.ObjectiveTo examine the effectiveness of current HNC screening programs in improving diagnosis and survival in adults.Evidence ReviewThis Preferred Reporting Items for Systematic Reviews and Meta-analyses–guided systematic review involved use of peer-reviewed, English-language journal articles identified from MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials between January 1, 2001, and July 15, 2022. Snowballing was applied to retrieve more studies. Eligible articles were original clinical trials and observational studies presenting a universal or risk-targeted screening program of primary HNC in the adult population. Reporting quality was assessed using the JBI’s critical appraisal tools.FindingsDatabase searches yielded 3646 unique citations with an additional 8 studies found via snowballing. Five reviewers assessed the full text of 106 studies. Sixteen articles were ultimately included in the review, involving 4.7 million adults (34.1%-100% male; median age, 30-59 years). Fifteen studies were based in Asia and 1 in Europe (Portugal). Five reported data from randomized clinical trials. An oral inspection conducted once or once every 2 to 3 years was described in 11 studies for screening oral cancer, while multistep screening involving Epstein-Barr virus serologic testing for nasopharyngeal carcinoma delivered every 1 to 4 years was presented in 5. In 4 trials and 6 observational studies, screening significantly increased the detection of localized (stage I/II) tumor or was associated with an increased proportion of diagnoses, respectively, regardless of the population and cancer subsites. Universal screening of asymptomatic adults improved 3- to 5-year overall survival but did not increase cancer-specific survival in 4 trials. Targeted screening improved overall and cancer-specific survival or was associated with improved survival outcomes in 2 trials and 2 observational studies, respectively. Studies had low to medium risks of bias.Conclusions and RelevanceEvidence from the existing literature suggests that a risk-targeted screening program for oral and nasopharyngeal cancers could improve diagnosis and patient survival. Screening adherence, societal cost-effectiveness, and optimal risk stratification of such a program warrant future research, especially in low-incidence settings outside Asia.