Head & neck cancers (HNC) can significantly impact health-related quality of life (HRQL), particularly functions such as speech, swallowing, & mouth opening. Clinical factors including tumour site, radiation treatment volume, & treatment modality may further influence outcomes. This study examined differences in symptom burden across tumour groups & evaluated the impact of these clinical factors on HRQL among individuals treated curatively for mucosal HNC. Patients aged ≥18, completed curative treatment with definitive or adjuvant radiation therapy (RT included. HRQL data were collected using EORTC QLQ-C30 & QLQ-HN35 between December 2020 & December 2025 during routine follow-up at Westmead & Blacktown Hospitals. Outcomes were grouped into 11 timepoints from first follow-up to over six years post-treatment. Multivariate general linear modelling assessed the effects of tumour site, RT treatment volume (primary only, primary with ipsilateral nodes, primary with bilateral nodes), & treatment modality (RT alone, chemoradiotherapy, surgery + RT ± chemotherapy). The study included 252 patients (mean age 64; 73% male). Significant differences in symptom burden across tumour groups were observed for swallowing, speech, social eating, social contact, cough, dyspnoea, sleep disturbance, financial difficulties (all p≤0.001), mouth opening (p=0.004), & dry mouth (p=0.031). Advanced larynx & oral cavity tumours showed greater speech difficulties, while oral cavity tumours had more social contact & mouth-opening issues. Chemoradiotherapy was associated with increased dyspnoea, & larger radiation volumes with greater social eating difficulties. Tumour–treatment interactions were observed for dry mouth, sticky saliva, & dyspnoea. Tumour site, treatment modality, & radiation volume are key predictors of HRQL in HNC. Larger irradiation volumes increase symptom burden, highlighting the need to integrate these factors into survivorship care & early interventions.