Cisplatin-Induced Ototoxicity in Head and Neck Cancer: A Systematic Review of Current Evidence, Clinical Implications, and the Need for Standardized Monitoring
Aurora Mirabile, Alert Vukatana, Mathilda Guizzardi, Giorgia Vaccarello, Leone Giordano, Raffaele AddeoBackground: Cisplatin-based chemoradiotherapy remains a standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC), but cisplatin-induced ototoxicity is common, usually irreversible and inconsistently monitored. Methods: MEDLINE, EMBASE and the Cochrane Library were searched for English-language clinical studies in adults published between January 2016 and January 2026. Primary full-text clinical studies reporting at least one hearing, tinnitus, vestibular or ototoxicity outcome were eligible; conference-only abstracts, duplicate reports, reviews and consensus papers were not. Twenty-four studies were retained from the original database route. A targeted supplementary PubMed verification performed on 16 September 2026 with broader auditory and vestibular terminology identified six additional eligible full-text studies, which were included through the PRISMA 2020 ‘other methods’ pathway, for a total of 30 studies. Risk of bias was appraised for all 30 studies with RoB 2, ROBINS-I and Joanna Briggs Institute (JBI) tools by a single review author; duplicate independent appraisal was not performed and is reported as a limitation. Meta-analysis had been planned but was not undertaken because audiometric frequencies, grading systems, follow-up intervals and effect measures were not comparable; this is reported as a protocol deviation. Results: The 30 studies comprised approximately 10,500 participants, although two reports used overlapping Hungarian patient samples and several studies included non-HNSCC populations. Reported ototoxicity ranged from 13% (severe, irreversible loss after weekly cisplatin with cochlear-sparing radiotherapy) to 72% (screen-detected loss in a survivorship clinic), reflecting different definitions rather than a single underlying rate. Comparative HNSCC cohorts consistently reported more hearing loss with 100 mg/m2 every three weeks than with weekly 40 mg/m2. Ten of the 30 studies were at high, serious or critical risk of bias, with one additional comparative study at moderate-to-serious risk; the long-term randomized comparison reported inferior locoregional control with weekly 30 mg/m2. Baseline hearing, cochlear radiation exposure, monitoring adherence and pharmacogenetic susceptibility were further determinants. Objective vestibular dysfunction was documented in the absence of dizziness. No pharmacological otoprotective strategy is established in adults. Conclusions: Cisplatin ototoxicity is a core survivorship endpoint. Weekly dosing may reduce hearing toxicity in selected settings but must not be read as universal oncological equivalence. Standardized definitions, baseline and longitudinal testing, cochlear-dose reporting and prospective evaluation of vestibular outcomes and otoprotective agents are the priorities.