From 07/01/2019 to 12/31/2019, 503 patients attended their routine follow-up appointments at the Department of Otolaryngology, Head & Neck Surgery of the University Hospital Erlangen. Out of these, 340 patients were included in the final analysis. A total of 163 patients (32.4%) were excluded due to various reasons: 57 did not return the questionnaire, 15 did not meet the inclusion criteria, 35 had missing UICC staging information, and 56 had other cancer types (i.e., skin cancer, lymphoma) not relevant to this study (see Fig. 1).

Out of the 340 patients examined, 52.9% (n = 180) were diagnosed at early stages (UICC I and II), while 47.1% (n = 160) were diagnosed at advanced stages (UICC III and IV) of HNC. The early-stage group had 21.7% females (n = 39) compared to 28.1% females (n = 45) in the advanced-stage group, though this difference was not statistically significant (p = 0.168). The average age at the time of the interview was 61.9 ± 12.3 years for the early-stage group and 63.7 ± 11.7 years for the advanced-stage group, with no significant difference between the two (p = 0.141). The mean time from initial diagnosis to the interview was 42.7 ± 37.3 months (range: 0–168) for early-stage patients and 46.2 ± 46.2 months (range: 0–248) for advanced-stage patients, also showing no significant difference (p = 0.240).

There were no significant differences between the groups regarding comorbidities: cardiovascular (p = 0.930), pulmonary (p = 0.437), oncological (p = 0.199), and neurological conditions (p = 0.204). The distribution of ECOG functional status was similar between the groups (p = 0.105), with the majority of patients in both groups having an ECOG score of 0 (80.3% in the early-stage group and 71.8% in the advanced-stage group).

Regarding cancer localization, the most common sites were the oropharynx (35.6%) and the larynx (31.1%) in the early-stage group, and the oropharynx (24.4%) and larynx (20.0%) in the advanced-stage group. However, hypopharyngeal carcinomas were significantly more prevalent in the advanced-stage group (15.0%) compared to the early-stage group (1.1%) (p < 0.001).

Treatment modalities varied significantly by cancer stage (p < 0.001). Early-stage patients were more likely to undergo surgery only (51.1%) compared to advanced-stage patients (15.0%). Conversely, advanced-stage patients more frequently received definitive radiochemotherapy (early-stage: 7.8% vs. advanced-stage: 30.0%) or multimodal therapy (surgery plus adjuvant radio(chemo)therapy) (early-stage: 40.0% vs. advanced-stage: 54.4%). Salvage surgery was rare and similar between groups (early-stage: 1.1% vs. advanced-stage: 0.6%).

The treatment intention was curative in 100% of the early-stage patients and 97.5% of the advanced-stage patients, with a statistically significant difference (p = 0.033). The rates of loco-regional recurrence were 9.0% in the early-stage group and 11.4% in the advanced-stage group (p = 0.322), while distant recurrence occurred in 1.1% of early-stage patients and none in advanced-stage patients.

In early-stage HNC patients, most reported minimal impairments in QoL domains, with the highest scores (indicating no issues) seen in chewing (80.7%), shoulder function (77.8%), and swallowing (64.9%). However, greater impairments were noted in taste (3.0% reporting complete loss, 7.2% moderate impairment) and saliva production (1.9% reporting no saliva, 10.7% significant reductions). Psychological issues, such as mood disturbances (11.2%) and anxiety (8.1%), were less frequent but present. Tables S1 & S2

In contrast, advanced-stage patients reported significantly greater impairments across domains. While chewing (70.7%), shoulder function (68.9%), and speech (52.7%) remained relatively preserved, taste and saliva were notably affected. Complete taste loss was reported by 5.6%, and severe reductions in saliva were reported by 28.7%, with 5.6% experiencing a total lack of saliva.

Psychological issues were also more prominent in advanced-stage patients, with anxiety reported by 48.7% and mood disturbances by 17.9%, reflecting a heightened burden in both physical and psychological domains.

Symptom severity comparisons between early-stage (UICC I + II, n = 180) and advanced-stage (UICC III + IV, n = 160) HNC patients revealed several statistically significant differences across key domains. Notably, pain, speech, mood, and anxiety showed no significant differences between the groups (p > 0.05). Table 2

Among the significant findings, the saliva domain demonstrated the most pronounced and clinically relevant difference (p < 0.001, η2 = 0.104), with early-stage patients reporting significantly less severe issues (Md = 100, IQR 70–100, M ± SD = 82.7 ± 25.5) compared to advanced-stage patients (Md = 70, IQR 30–100, M ± SD = 64.4 ± 31.7). The clinically meaningful difference of more than 18 points underscores the significant impact of advanced-stage disease on saliva production and QoL.

The appearance domain also showed a substantial difference (p = 0.003, η2 = 0.038), with early-stage patients reporting better scores (Md = 100, IQR 75–100, M ± SD = 86.2 ± 19.1) than advanced-stage patients (Md = 75, IQR 75–100, M ± SD = 78.5 ± 20.4). This difference is clinically meaningful, reflecting the higher physical and emotional burden experienced by advanced-stage patients related to appearance.

Further significant differences were noted in swallowing (p = 0.003, η2 = 0.038), with early-stage patients again reporting fewer issues (Md = 100, IQR 75–100, M ± SD = 88.7 ± 17.7) than advanced-stage patients (Md = 75, IQR 75–100, M ± SD = 80.8 ± 18.9). This difference also reached a clinically meaningful threshold, highlighting the increased swallowing difficulties in advanced-stage patients, likely due to more intensive treatments.

Other domains with significant differences included activity (p = 0.005, η2 = 0.034), recreation (p = 0.004, η2 = 0.037), chewing (p = 0.043, η2 = 0.018), shoulder function (p = 0.011, η2 = 0.029), and taste (p = 0.009, η2 = 0.030), where early-stage patients generally reported less severe symptoms. These differences, although statistically significant, had smaller effect sizes compared to saliva, swallowing, and appearance, yet still reflect the greater impairments in QoL domains faced by advanced-stage patients..

In contrast, for symptoms such as pain, speech, mood, and anxiety, despite differences observed, these did not reach statistical significance, and the clinical relevance of these differences remains uncertain.

Patients with early-stage disease reported significantly better physical scores (Md = 90.8, IQR 76.6–100, M ± SD = 86.6 ± 14.1) than those with advanced-stage disease (Md = 79.1, IQR 68.3–90.8, M ± SD = 78.6 ± 14.6), with a statistically significant difference (p < 0.001, η2 = 0.076). Similarly, early-stage patients fared better in terms of socioemotional well-being (Md = 84.1, IQR 74.1–95.8, M ± SD = 81.9 ± 16.1) compared to advanced-stage patients (Md = 79.1, IQR 61.6–90.8, M ± SD = 75.7 ± 17.6). The difference was statistically significant (p = 0.003, η2 = 0.042), though the effect size was smaller than in the physical domain.

When comparing health-related QoL to pre-cancer status, no statistically significant difference was observed between early- and advanced-stage patients (p = 0.162, η2 = 0.009), with both groups showing similar medians (early-stage: Md = 50, IQR 25–100, M ± SD = 53.9 ± 33.8; advanced-stage: Md = 50, IQR 25–75, M ± SD = 47.2 ± 35.7).

Both groups reported similar health-related quality of life (HRQoL) over the past 7 days, with no significant difference between early-stage and advanced-stage patients (p = 0.168, η2 = 0.009). Early-stage patients had a median HRQoL score of 60 (IQR 40–80, M ± SD = 56.9 ± 22.9), while advanced-stage patients reported a lower median score of 40 (IQR 40–60, M ± SD = 52.1 ± 20.3), though this difference was not statistically significant.

Both groups reported similar overall QoL scores in the past 7 days, with no significant difference (p = 0.089, η2 = 0.014). Early-stage patients had a median score of 60 (IQR 40–80, M ± SD = 61.4 ± 22.2), while advanced-stage patients reported a median of 60 as well (IQR 40–80, M ± SD = 56.9 ± 21.8). Table 3