Outcomes and Toxicities of Radiation Therapy in HIV-Positive Patients With Head and Neck Cancer: A Systematic Review.

People living with HIV (PLWH) have an increased incidence of head and neck cancer (HNC), yet the impact of HIV on radiation therapy (RT) outcomes remains poorly defined. To our knowledge, no prior systematic review has synthesized this evidence. A systematic review was conducted following PRISMA 2020 guidelines and prospectively registered on PROSPERO (CRD420251075908). PubMed was searched from inception to July 2025, with an updated search in May 2026 yielding no additional studies. Eight retrospective studies comprising 185 patients were included, all from the United States. Tumor subsites included the oral cavity, oropharynx, larynx, paranasal sinus, and facial skin, with squamous cell carcinoma and Kaposi sarcoma as the predominant histologies. Treatment techniques ranged from conventional radiotherapy in earlier series to intensity-modulated radiotherapy in more contemporary cohorts. In curative-intent cohorts, 3-year overall survival ranged from 55% to 78% and local control from 69% to 92%. Grade ≥3 acute toxicity, including mucositis, dermatitis, and dysphagia, was common but not clearly disproportionate to HIV-negative populations. Treatment interruption rates appeared elevated, with up to 42% of patients experiencing breaks exceeding 10 cumulative days in one series. Reporting of CD4 count, viral load, and HPV/p16 status was inconsistent. Methodological quality was low to moderate, and clinical heterogeneity precluded meta-analysis. These findings suggest that curative-intent RT for HNC in PLWH is feasible with meaningful disease control. Antiretroviral therapy optimization and multidisciplinary co-management are essential. Prospective, multicenter studies with standardized reporting, matched controls, and inclusion of high HIV-prevalence settings are needed to define optimal treatment strategies.