The effect of photodynamic therapy in head and neck cancer: A comprehensive review of in vivo models

Abstract

Photodynamic therapy (PDT) is a minimally invasive treatment that combines a photosensitizer, light, and oxygen to induce localized oxidative stress, resulting in tumor cell death, vascular damage, and immune modulation. This review aimed to summarize the effects of PDT on tumor progression in in vivo models of head and neck cancer. A systematic search was performed across PubMed/MEDLINE, Embase, Scopus, SciELO, and LILACS for studies published between 2015 and 2026, following PRISMA‐ScR guidelines and the PICO framework. Eligible studies included animal models with head and neck tumors treated with PDT using non‐conjugated photosensitizers. Extracted outcomes included tumor growth, survival rates, histological and molecular changes, immune activation, and adverse effects. Quality assessment was achieved by SYRCLE tools. Preliminary analysis indicates that PDT with different photosensitizers can reduce tumor growth, prolong survival, increase tumor cell death, decrease proliferation and angiogenesis, induce reactive oxygen species production, and modulate immune responses in preclinical models, without apparent toxicity. Despite these promising results, methodological heterogeneity and insufficient dosimetric reporting limit reproducibility. Overall, these findings highlight the therapeutic potential of PDT with different photosensitizers in head and neck preclinical studies and underscore the need for standardized protocols to improve reproducibility and support clinical translation.