Background: There is considerable post-treatment morbidity in survivors of head and neck cancer (HNC) despite improved survival following multimodality therapy. Assessment of health-related quality of life (HR-QoL) gives valuable information about functional and psychosocial sequelae of radiation therapy (RT), especially in less-studied populations such as South Asians.

Method: A prospective observational study was conducted between August 2023 and December 2024, including biopsy-proven HNC patients receiving curative-intent RT (definitive or adjuvant). The EORTC QLQ-HN35 questionnaire (Urdu/English, interviewer-assisted) was administered at baseline and 12 ± 2 weeks post-RT. Mean ± standard deviations were calculated for each domain. Pre- and post-treatment differences were analysed using paired t-tests, while multivariate analysis (general linear model-multivariate analysis of variance) identified factors associated with HR-QoL outcomes.

Results: Fifty-six patients (mean age, 49 ± 13 years; male sex, 78.6%) were included in the analysis. There was a marked deterioration of xerostomia (p = 0.004), pain (p = 0.011) and taste/smell (p = 0.018), whereas social contacts (p = 0.048) and sexuality (p < 0.001) improved after therapy. Tumour site (p < 0.001), histological subtype (p < 0.001) and marital status (p < 0.001) were the main HR-QoL predictors detected. Both oropharyngeal/hypopharyngeal locations were related to more post-treatment pain and social-eating problems.

Conclusion: Within 3 months after curative-intent RT, HNC patients showed worsening of xerostomia, pain and sensory loss, with the improvement in social contact and sexuality. Tumour site, histopathology and marital status were the key predictors of HR-QoL, demonstrating anatomical, biological and psychosocial influences. Targeted follow-up and supportive care are important for future studies integrating patient-reported and objective outcomes to personalise survivorship care.