Targeted Screening Strategies for Head and Neck Cancer: A Global Review of Evidence, Technologies, and Cost-Effectiveness.

Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence particularly in oropharyngeal cancer subsites. Despite well-known risk factors, such as tobacco and alcohol consumption as well as human papillomavirus (HPV) infection, most HNCs are diagnosed at an advanced stage, resulting in poor prognosis. Early detection and screening are critical, especially in high-risk populations. Nevertheless, there is a lack of guidelines for a stratified HNC screening. A systematic literature review was conducted following PRISMA guidelines, using PubMed and ScienceDirect databases up to 30 June 2025. Search terms included "screening", "early diagnosis", and specific HNC subsites. A total of 199 records were screened, and 160 studies were included based on relevance and scientific rigor. The review concentrates on contemporary screening modalities, stratification of high-risk cohorts, emerging technologies, and cost-effectiveness evidence. Visual inspection and panendoscopy remain the standard tools for HNC screening, but have limited effectiveness and cost-efficiency. Opportunistic screening in high-risk individuals, especially in regions with high HNC prevalence, has shown benefits. Liquid biopsy techniques targeting HPV- and Epstein-Barr virus-related HNC demonstrate high sensitivity for early detection and recurrence monitoring. Novel imaging technologies like narrow-band imaging and Raman spectroscopy show promising diagnostic accuracy but require further validation. Most broad-based screening programs lack cost-effectiveness, while targeted strategies in high-risk groups appear more viable. Screening for HNC should be stratified by individual risk profiles and regional disease prevalence. Emerging technologies, particularly liquid and optical biopsy techniques, offer transformative potential. Future screening strategies must integrate technological advances into tailored, evidence-based protocols to improve early detection and patient outcomes in HNC.