Quality of life assessment in head and neck cancer patients undergoing radiation therapy in a tertiary referral university hospital

Mariam Hina¹, Bilal Mazhar Qureshi¹, Habiba Zaheer², Bilal Ahmed¹, Maham Khan¹, Laraib Khan¹, Tooba Ali¹, Fabiha Shakeel¹, Jawad Ahmad³, Muhammad Abdul Wasay Zuberi³, Maria Tariq¹, Nasir Ali¹, Asim Hafiz¹ and Ahmed Nadeem Abbasi¹

¹Section of Radiation Oncology, Department of Oncology, Aga Khan University, Karachi 74800, Pakistan

²Department of Oncology, Aga Khan University, Karachi 74800, Pakistan

³Dow University of Health Sciences, Karachi 74200, Pakistan

Abstract

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.

Keywords: radiation therapy, multidisciplinary care, adjuvant treatment, head and neck cancer, acute side effects, late side effects, quality of life, survivorship, psychosocial re-integration, targeted follow-up

Correspondence to: Mariam Hina
Email: hinasyed95@gmail.com

Published: 01/09/2026
Received: 29/03/2026

Publication costs for this article were supported by ecancer (UK Charity number 1176307).

Copyright: © the authors; licensee ecancermedicalscience. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction

Survivorship in head and neck cancer (HNC) is increasing due to the changes in the epidemiology of the disease and improvement in the treatment efficacy [1]. Five-year survival rates for patients with non-metastatic disease are currently between 60% and 80% [2]. Treatment of HNC is multidisciplinary and includes combination of surgery, radiation and chemotherapy. Radiation therapy (RT) is an integral part of treatment, either in a definitive or an adjuvant setting [3]. Patients are therefore vulnerable to RT-related adverse effects ranging from immediate side effects such as mucositis during treatment to long-term effects such as xerostomia and dysphagia after therapy [4–6]. These adverse effects significantly compromise patients’ functional abilities, overall quality of life, psychological and emotional wellbeing [7, 8]. As a result, HNC survivors have diverse post-treatment needs, and evaluation of health-related quality of life (HR-QoL) is therefore particularly significant in this population [9, 10]. Even though 40% of the global HNC burden arises in South Asia [11, 12], HRQoL in this population remains relatively underexplored, mainly due to the variations in the measurement tools and lack of comprehensive assessment strategies [13].

Various clinically reliable and validated modules and questionnaires have been developed to assess the HRQoL of patients during or after treatment [14]. These tools address different aspects of HRQoL and include generic tools, cancer-specific questionnaires (the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire, version 3.0/EORTC QLQ-C30) and cancer-site specific modules (the head and neck module in EORTC/EORTC QLQ-HN35) [15–17]. The EORTC QLQ-HN35 is one of the most widely accepted, site-specific cancer modules as it depends on the patient’s own assessment rather than perceived pre- and post-treatment changes [16, 18].

The objective of this study was to evaluate the HRQoL in HNC patients both before and 12 ± 2 weeks after the completion of RT, using the EORTC QLQ-HN35 questionnaire. The purpose of this evaluation is to identify factors that significantly impact patients’ routine functioning and improve treatment outcomes for this patient group. The 12 ± 2 weeks post-treatment interval was chosen to ensure feasible data collection while minimising loss to follow-up and to capture both the early recovery phase following treatment and persistent treatment-related effects that may continue to influence the quality of life. Given the high prevalence of HNC in the South Asian population, this study holds strong relevance for this group.

Method

A prospective observational study was conducted between August 2023 and December 2024 at our institute. The study included all biopsy-proven HNC cases receiving curative-intent RT, either definitive or adjuvant. Eligible participants were aged ≥18 years, had an ECOG ≤2, and were able to understand and respond to the questionnaire in either English or Urdu-validated version, as per their preference [19]. Patients with distant metastasis, prior HN RT, concurrent malignancy, cognitive impairment or those with incomplete treatment were excluded from the study. Participants completed the EORTC QLQ-HN35 questionnaire via interviewer-assisted administration at two time points: baseline (prior to treatment planning and before undergoing CT simulation) and post-RT follow-up assessment at 12 ± 2 weeks. Missing responses were handled according to the EORTC Scoring Manual, allowing computation of mean scores when at least 50% of items in a scale were completed.

Ethical approval for the study was obtained from the Institutional Review Board (IRB) (2023-8578-25701). Written informed consent was obtained from all participants prior to enrolment.

Data were analysed using IBM SPSS v23. Descriptive statistics were used for demographic and clinical variables. Mean and standard deviation (SD) were reported for continuous variables, while categorical variables were expressed as frequencies and percentages. Paired-sample t-test was used to make comparisons between pre- and post-treatment HRQoL scores. General linear model (GLM) multivariate analysis of variance (MANOVA) was used to analyse the correlations between the factors and the HR-QoL scales. A p -value <0.05 was considered statistically significant.

Instruments of HR-QoL

The EORTC QLQ-H&N35 questionnaire was obtained from the Quality-of-Life Unit, EORTC Data Center in Brussels, Belgium. The QLQ-H&N35 particularly assesses HR-QoL symptoms in HNC patients. It incorporates seven multiple-item scales: pain, swallowing ability, senses (taste/smell), speech,

social eating, social contact and sexuality. Also included are six single-item scales: problems associated with teeth, mouth opening, dry mouth, sticky saliva, coughing and feeling ill. Each scale score ranges from 0 to 100, with higher scores indicating greater symptom severity.

Statistical analysis

Mean ± SDs for each HR-QoL scale were computed in accordance with the EORTC QLQ scoring manual. Paired t-tests were used to compare pre- and post-treatment scores. GLM MANOVA was used to see the association between clinical factors and the HR-QoL scales. The GLM-MANOVA approach was used to test the hypothesis of a significant association between a set of interrelated dependent variables (HR-QoL scales) and independent variables.

To investigate the association of a given factor with HR-QoL scales, a univariate analysis was conducted to establish whether the factor was associated significantly with any of the HR-QoL scales. Wilks’ l was used to test the impact of each variable included in the model. All variables were entered into the multi-factor model. In the case of a significant association between a factor and all HR-QoL scales taken together, a second ANOVA was performed to investigate the association between that prognostic factor and each HR-QoL scale separately, with post hoc testing using the Bonferroni method with a p -value.

Being the most concerned scale of HR-QoL in the study, pain was further analysed by multiple linear regression models to explore its associated prognosticators. All the data processing was performed using the statistical software SPSS for Windows (version 27).

Results

Study population

A total of 56 patients diagnosed with HNC undergoing RT were enrolled in the study. Patients had an average age of 49.03 years (range: 20–79 years); the majority were male (44 patients, 78.6%) versus female (12 patients, 21.4%). Most were married (51; 91.1%). Squamous cell carcinoma was the predominant histology (49; 87.5%). The oral cavity constituted the predominant tumour location (35; 62.5%), followed by the oropharynx (5; 8.9%) and the larynx (4; 7.1%) (Table 1). All patients successfully received curative RT using the volumetric modulated arc therapy (VMAT) technique. The domains and scoring structure of the questionnaire are detailed in Table 2.

Outcomes of HR-QoL

In Table 3, the descriptive statistics indicate both symptoms worsening and improvement across different domains of the QLQ-H&N35. Several symptom scales demonstrated a notable increase in mean scores post-RT, reflecting a deterioration in symptom burden. These included dry mouth (xerostomia); the mean score increased from 11.3 pre-treatment to 24.4 post-treatment (∆ [post−pre] = +13.1). Pain increased from 10.5 to 17.8 (∆ [post−pre] = +7.3), senses (taste/smell) from 3.27 to 7.14 (∆ [post−pre] = +3.87), feeling ill from 11.3 to 16.6 (∆ [post−pre] = +5.3) and difficulty in opening mouth from 17.2 to 20.8 (∆ [post−pre] = +3.6), indicating treatment-related aggravation of discomfort.

Conversely, several functional domains exhibited improvement, suggesting recovery in psychosocial and communicative aspects following treatment completion. These included speech problems: 12.1–8.13 (∆ [post−pre] = −3.97), social contact improvement: 15.0–10.3 (∆ [post−pre] = −4.7), coughing: 5.95–3.57 (∆ [post−pre] = −2.38) and sticky saliva: 9.52–6.54 (∆ [post−pre] = −2.98). A modest enhancement was also observed in sexual factors; the mean score declined slightly from 5.05 to 4.46 (∆ [post−pre] = −0.59), reflecting better psychosocial reintegration.

Table 1. Patient characteristics.

Table 2. Frequency and percentage distribution of survey responses.

Inferential analysis using paired t-tests (Table 4) further delineated the statistical significance of these changes. About 5 of the 13 scales demonstrated statistically significant pre- to post-treatment differences (Figure 1). Significant symptom worsening was observed for pain (95% CI [–12.84, –1.74], p = 0.011), dry mouth (95% CI [–21.72, –4.47], p = 0.004) and senses (taste/smell) (95% CI [–7.05, –0.69], p = 0.018), confirming that RT exerted a measurable adverse impact on these domains. In contrast, significant functional improvements were detected for social contact (95% CI [0.05, 9.23], p = 0.048) and sexual factors (95% CI [–2.70, 3.89], p < 0.001), reflecting enhanced psychosocial adjustment following treatment. The remaining domains, such as swallowing, teeth, opening mouth, sticky saliva, coughing, speech, feeling ill and social eating, did not reach statistical significance (all p > 0.05), suggesting that the observed mean differences in these scales likely represent random variation rather than a consistent RT effect.

Table 3. Calculated pre- and post-radiotherapy scores of EORTC QLQ-H&N35 scales for HNC survivors.

Table 4. Comparison of pre- and post -radiotherapy EORTC QLQ-H&N35 scale scores using paired t-test.

Figure 1. Mean change in EORTC QLQ-HN35 symptom domains at 3 months post-radiotherapy with corresponding 95% confidence intervals (CI) and p-values. The green line represents the lower CI limit, the blue line represents the upper CI limit and the yellow line indicates the p-values for each symptom domain. Significant functional improvements were detected for social contact and sexual factors.

Variables associated with HR-QoL outcomes

In the first step of the GLM-MANOVA, the association between the independent variables (three sociodemographic and seven clinical variables) and the dependent variables (scales of QLQ-H&N35) was investigated (one-factor model, Table 5). This analysis showed that four of the ten variables (except the age, p = 0.324; gender, p = 0.399; AJCC stage, p = 0.377; definitive therapy/surgical resection, p = 0.357; adjuvant therapy, p = 0.763; radiation phase, p = 0.074) were associated with the overall outcome on QLQ-H&N35. The ten variables were then entered into the multifactor model analysis, which demonstrated that histopathological diagnosis and tumour site were the most influential determinants of HR-QoL, exhibiting highly significant effects in both models (histopathology: Wilk’s λ = 0.081, p = 0.007 in the one-factor model; λ = 0.012, p < 0.001 in the multifactor model; tumour site: Wilk’s λ = 0.040, p < 0.001 in the one-factor model; λ = 0.003, p < 0.001 in the multifactor model). Marital status also emerged as a significant psychosocial determinant, achieving greater significance in the multifactor model (Wilk’s λ = 0.052, p < 0.001) compared to the one-factor model (Wilk’s λ = 0.422, p = 0.037), indicating that social support plays a vital, independent role in post-treatment adaptation and recovery (Table 5).

The site of tumour also exerted a significant influence on certain HR-QoL scales, including pain (F (7,48) = 2.38, p = 0.035, partial η² = 0.258), feeling ill (F (7,48) = 4.08, p = 0.001, partial η² = 0.373) and social eating (F (7,48) = 2.46, p = 0.030, partial η² = 0.265). Patients with oropharyngeal and hypopharyngeal tumours exhibited worse pain and social eating scores compared with those with nasopharyngeal or thyroid lesions,

suggesting that tumour location plays a considerable role in determining post-treatment functional outcomes and overall HR-QoL. In contrast, the adjuvant chemotherapy variable showed a significant effect only for the feeling ill scale (F (1,54) = 4.06, p = 0.049, partial η² = 0.070), with patients receiving adjuvant chemotherapy reporting greater levels of general malaise following treatment.

Additional analysis of pain-associated variables using multiple linear regression (Table 6) identified several significant predictors. Marital status showed a significant correlation with pain (β = 11.53, p = 0.048), with married individuals reporting elevated pain levels compared to widowed or single patients. Histopathological type also proved significant (β = 5.40, p = 0.022), revealing that squamous cell carcinoma patients experienced more severe pain than those with alternative tumour types.

Discussion

Assessment of HR-QoL at 12 weeks following RT

The current research investigated HR-QoL at the beginning of treatment and 12 ± 2 weeks after the conclusion of curative RT. This specific 12 ± 2 weeks assessment period was chosen because it represents a transition in early survivorship; during this time, acute side effects from radiation typically start to subside, while more persistent symptoms related to the treatment remain evident. This timeframe thus offers a valuable window to study the balance between treatment-induced morbidity and the return of functional health. The reason for using EORTC QLQ-HN35 is its wide acceptance and high compliance, as it provides patient assessment-based scoring for specific adverse effects and does not underestimate a patient’s own assessment of their pre-treatment physical performance as compared to post-treatment [16,18].

Table 5. GLM-MANOVA test of the overall effect of the sociodemographic and clinical variables on the EORTC QLQ-H&N35 scales.

Table 6. Multiple linear regression analysis for pain.

Overall HR-QoL pattern at 12 weeks

Throughout the 12 ± 2 weeks following RT, patients exhibited a varied HR-QoL profile. There was a notable decline in areas such as dry mouth (xerostomia), pain levels and sensory abilities, particularly taste and smell. In contrast, domains related to social engagement and sexual health showed marked improvement. These results imply that while physical toxicities from treatment continue to impact survivors in the early post-therapy stage, psychosocial healing may initiate shortly after the treatment cycle ends [20].

Worsening of xerostomia, pain and sensory function

Among all evaluated domains, xerostomia demonstrated the greatest deterioration with mean scores increasing from 11.3 at baseline to 24.4 at 12 ± 2 weeks (Δ = +13.1, p = 0.004). This finding is consistent with the known vulnerability of salivary glands to RT because of their critical location and reflects the persistence of salivary dysfunction beyond treatment completion. Since saliva plays a critical role in swallowing, taste perception, oral hygiene, nutritional intake and speech, xerostomia remains one of the most clinically relevant determinants of post-treatment QoL in HNC survivors [21–23].

Pain also worsened significantly during the study period. It increased from a mean score of 10.5 before treatment to 17.8 at 12 ± 2 weeks (Δ = +7.3, p = 0.011). Persistent pain during this phase reflects ongoing mucosal healing, neuropathic injury, residual treatment-related inflammation and fibrosis. Similar findings have been reported in previous studies evaluating early post-RT recovery, highlighting the need for continued symptom monitoring beyond treatment completion [24].

Likewise, sensory dysfunction increased significantly, with taste and smell scores worsening from 3.3 to 7.1 (Δ = +3.9, p = 0.018). Alterations in taste and smell substantially affect appetite, nutritional status and overall patient satisfaction. Given that recovery of sensory function often extends over several months, the persistence of these symptoms at 12 ± 2 weeks is not unexpected [25].

Improvement in psychosocial domains

While physical symptoms worsened, psychosocial areas showed encouraging signs of progress. Social interaction scores improved from 15.0 at baseline to 10.3 at follow-up (Δ = −4.7, p = 0.048), and sexual health scores also saw a significant boost. These findings suggest that patients begin to reintegrate into their social lives once the intensive treatment phase is over.

Gains in social functioning stem from increased public confidence, better communication with family and fewer disruptions to daily routines [26]. Likewise, improvements in sexual health reflect a recovery in emotional well-being, self-regard and interpersonal connections. Altogether, these results emphasise that survivorship involves not just managing physical symptoms but also restoring emotional and social health [27, 28].

Determinants of HR-QoL at 12 weeks

The location of the tumour was found to be a major predictor of HR-QoL results. Patients with cancers in the oropharynx or hypopharynx suffered from significantly higher levels of pain, more difficulty with social eating and a greater sense of illness than those with tumours in other areas. This reflects the anatomical and functional burden of treating pharyngeal subsites [29].

Marital status was also an independent factor influencing pain and HR-QoL outcomes. The importance of marital status in the analysis highlights the critical role that social support plays during the recovery process. Patients with robust support networks are better prepared to handle treatment side effects, adjust to physical limitations and manage the general challenges of being a cancer survivor [30].

Clinical implications

The results of this study suggest that survivorship programs should go beyond disease monitoring to include early, multidisciplinary support. This should encompass symptom management, nutritional guidance, physical rehabilitation and psychological support, especially for patients at high risk of poor HR-QoL. Specific attention is needed for those with pharyngeal tumours or those who lack strong social support systems.

Strengths

This study is strengthened by its prospective design, assessment of HR-QoL changes from baseline to post-treatment within the same patient cohort with reduced recall bias. In addition, the use of the validated EORTC QLQ-HN35 questionnaire, interviewer-assisted bilingual administration and a relatively uniform VMAT-based curative-intent treatment approach provided a reliable evaluation of early survivorship outcomes in a South Asian population, an area where such data remain limited.

Limitations

As a single-centre study with a relatively small sample size, the findings may have limited generalisability. Furthermore, the 12 ± 2 weeks follow-up was designed to evaluate early survivorship and therefore does not capture long-term recovery patterns. Objective functional assessments, including swallowing evaluation, salivary flow measurements, nutritional assessment and trismus evaluation, were not performed, precluding correlation of patient-reported outcomes with functional recovery. Finally, the absence of a concurrent global HR-QoL instrument and minimally clinically important difference thresholds may limit interpretation of the clinical relevance of the observed changes.

Conclusion

This prospective study identified that within 3 months after curative-intent RT, HNC patients exhibited a significant aggravation of xerostomia, pain and sensory loss, while also showing significant improvement in the social contact and sexuality domains. Tumour site, histopathological subtype and marital status emerged as the strongest predictors of HR-QoL, emphasising the significance of anatomical, biological and psychosocial factors in determining survivorship outcomes. These results emphasise the need for targeted follow-up and individualised supportive interventions.

Recommendations

Future research should utilise multicentre, longitudinal designs with larger groups and repeated HR-QoL checks at 3, 6 and 12 months or longer. Although patient-reported QoL scores capture the subjective experience of symptoms and recovery, the integration of these measures with objective functional endpoints, such as assessments of swallowing efficiency, salivary flow and trismus, would provide a more comprehensive and reliable method of assessing the impact of treatment. Furthermore, early involvement of multidisciplinary teams and structured survivorship interventions, such as salivary-sparing RT techniques, swallowing rehabilitation programmes and symptom-triggered psychosocial support, should also be a priority in future research in high-risk subgroups. This would offer the potential to achieve personalised, data-driven, evidence-based survivorship care for HNC patients.

Conflicts of interest

The authors have no relevant financial or non-financial interests to disclose.

Funding

No funding was received for conducting this study.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Ethical approval

This study was conducted in accordance with institutional ethical standards. Approval was obtained from the Institutional Ethics Review Committee prior to data collection.

Author contributions

Mariam Hina: substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafting the article and revising it critically for important intellectual content.

Bilal Mazhar Qureshi: substantial contributions to analysis and interpretation of data; drafting the article and reviewing it critically for important intellectual content.

Habiba Zaheer: substantial contributions to the critical review of the article for important intellectual content.

Bilal Ahmed: revised the draft critically for important intellectual content.

Maham Khan: revised the draft critically for important intellectual content.

Laraib Khan: revised the draft critically for important intellectual content.

Tooba Ali: revised the draft critically for important intellectual content.

Fabiha Shakeel: revised the draft critically for important intellectual content.

Jawad Ahmad: substantial contributions to the analysis and interpretation of data.

M. Abdul Wasay Zuberi: substantial contributions to analysis and interpretation of data.

Maria Tariq: revised the draft critically for important intellectual content.

Nasir Ali: revised the draft critically for important intellectual content.

Asim Hafiz: revised the draft critically for important intellectual content.

Ahmed Nadeem Abbasi: substantial contributions to conception and design, acquisition of data, analysis and interpretation of data; drafting the article and revising it critically for important intellectual content.

Data availability

The datasets generated and/or analysed during the current study are stored in an institutional repository available from the corresponding author on reasonable request.

Use of artificial intelligence

The authors confirm that no artificial intelligence-assisted technologies were used in the generation of the data/scientific content of this manuscript. All content, analysis and conclusions are solely those of the authors.

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