1. Introduction
Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 700,000 new cases each year worldwide, making it the eighth most common malignancy [
1]. Most patients are diagnosed with a locally advanced disease requiring complex multi-modal treatments that involve surgery or sometimes multiple surgeries, either with or without reconstruction procedures; radiotherapy (RT); or chemo radiotherapy (CRT) [
1,
2]. Adequate synergy between the needs of patients and the consultations, interventions, and care provided by the medical team is essential for improving the overall management of HNSCC [
3,
4].
Quality of life is defined by the WHO as “individuals’ perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns” [
5]. It is a broad-ranging concept incorporating in a complex way the person’s physical health, psychological state, level of independence, social relationships, personal beliefs, and relationships to salient features of the environment [
5].
In recent years, the measurement of health has expanded beyond traditional health indicators, such as mortality and morbidity, to include measures of the impact of disease and impairment on daily activities and behaviour [
6], perceived health measures [
7], and disability/functional status measures [
8]. These measures, whilst beginning to provide a measure of the impact of disease, do not assess quality of life per se, which has been aptly described as “the missing measurement in health” [
9]. HRQoL (health-related quality of life) is more specific and allows medical professionals to appreciate the impact of disease and treatment on the patient psychologically, physically, and socially [
5,
9].
The EORTC quality-of-life questionnaire (QLQ) is an integrated system for assessing the health-related quality of life (HRQoL) of cancer patients participating in international clinical trials [
9]. The core questionnaire QLQ-C30, which we used in our study (See
Supplementary Materials), is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status/QoL scale, and six single items. Each of the multi-item scales includes a different set of items—no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus, a high score for a functional scale represents a high/healthy level of functioning, a high score for the global health status/QoL represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems. The scaling technique described above is based upon the widely applied Likert method of summated scales, in which the constituent items within each scale are simply summed. This makes several assumptions about the nature of the items, the most important of which are (a) that it is appropriate to give equal weight to each item and (b) that each item is graded on a linear or equal-interval scale. The raw QLQ-C30 scores can be transformed to scores ranging from 0 to 100 [
10].
The rationale for using the EORTC QLQ was based on our experience with general population data based on large random samples from the general population in Norway, Sweden, and Denmark. The questionnaire is also accompanied by a Summary Booklet with examples of the use of statistical packages and the EORTC QLQ-C30 Reference Values Manual [
10].
In summary, QoL scales can become reference tools for a longitudinal follow-up of head and neck cancer patient cohorts and can even inspire physicians to adapt and improve treatments according to patients’ socio-economical features.
Aim
An assessment of QoL–general health and well-being, physical activity, role functioning, emotional functioning, cognitive functioning, social functioning, and symptom scales at a 3-year follow-up after surgical HNSSC treatment—and a comparison between the 3-year results and admission values.
3. Results
Of 251 HNSCC patients diagnosed in an advanced stage (IVa) and treated in one year (2019) at Coltea Clinical Hospital, only 38% (N = 95) survived until the 3-year follow-up. Of those who did survive, 6 patients were lost at the 3-year follow-up. The group distribution was as follows: 41 patients with laryngeal first involvement (46.1%), 20 patients with hypopharyngeal first involvement (22.5%), 15 patients with oropharyngeal first involvement (16.9%), and 13 patients with oral cavity first involvement (14.6%) (
Table 1).
The American Joint Committee on Cancer (AJCC)’s TNM classification system was used, and the results are summarized in
Table 2 and
Table 3.
The patients’ demographic characteristics were as follows: 78 patients were men (87.6%), and 11 were women (12.4%); the median age was 58 years; 72 patients were smokers (80%); 45 patients admitted to heavy alcohol consumption (50%); 29 patients had previous morbidities (32%)—cardiovascular diseases, diabetes mellitus, hepatitis, or pulmonary tuberculosis; 8 patients had previous RT (9%), and the rest of them had RT postoperatively; and 3 patients (3%) had CHT previously (all from the pharyngeal group). The sex distribution, TNM, and morbidities are shown below (
Table 4 and
Table 5).
All cases were discussed by the hospital’s tumour board, which guided the final treatment, and they all gave their informed consent for surgery. We do not have data regarding the HPV status of the entire group.
Good general health was reported by 80% of the patients, and 75% thought that their health was the same as or better than it was prior to the treatment.
At admission, the total laryngectomy group (larynx and hypopharyngeal sites of involvement), N = 61, reported the mean value of the following scales: QoL and general health and well-being, 41.7; physical activity, 60; role functioning, 66.7; emotional functioning, 41.7; cognitive functioning, 50; social functioning, 66.7 (
Figure 1). On the symptom scale, they reported fatigability, pain, insomnia, dyspnoea, and financial difficulties.
A total of 84% (N = 51) of the patients suffered a total laryngectomy with primary vocal prosthesis (VP) placement through a tracheo-oesophageal fistula, and 16% (N = 10) of them were guided to learn to use their oesophageal voice or to use an electrolarynx.
At the 3-year follow-up, the VP group reported a mean value of 75 for the QOL and general health and well-being scale, 86.7 for physical activity, 66.7 for role functioning, and 100 for emotional, cognitive, and social functioning (
Figure 1). They still reported an 11.1 on the scale for fatigability, 16.7 for pain, 33.3 for dyspnoea, 66.7 for insomnia, and 100 for digestive symptoms (constipation and/or diarrhea). As for symptoms, they reported sticky saliva and coughing (75%). In contrast, the patients without VP reported a mean value of 60 on the scale for QOL and general health and well-being, 60 for physical activity, 33.3 for role functioning, 50 for emotional functioning, 66 for cognitive functioning, and 33.3 for social functioning. They reported an 11.1 on the scale for fatigability and 66.7 for digestive symptoms (constipation and/or diarrhea), with a value of 50 for financial difficulties.
The oropharyngeal group, N = 15, reported at admission the following mean scales: QOL and general health and well-being, 25; physical activity, 46.7; role functioning, 33.3; emotional functioning, 25.0; cognitive and social functioning, 33.3. On the symptom scale, pain and insomnia were the most-reported symptoms. At the 3-year follow-up, patients reported the following mean scales: 41.7 for QOL and general health and well-being, 60.0 for physical activity, 33.3 for role functioning, 41.7 for emotional functioning, 50.0 for cognitive functioning, and 66.7 for social functioning (
Figure 2). The symptom scales at the 3-year follow-up reported pain, dry mouth, and difficulties in opening the mouth.
The oral cavity group, N = 13, of which 10 required partial mouth-floor resection and some form of mandibulectomy, reported at admission the following mean scales: QOL and general health and well-being, 33.3; physical activity, 60.0; role functioning, 60; emotional functioning, 60; cognitive functioning, 75; and social functioning, 75. At the 3-year follow-up, they reported 41.0 for QOL and general health and well-being, 53.3 for physical activity, 33.3 for role functioning, 25.0 for emotional functioning, 33.3 for cognitive functioning, and 33.3 for social functioning (
Figure 3). The symptom scales reported at the 3-year follow-up were pain, difficulties in opening the mouth, sticky saliva, and social contact.
4. Discussion
A quantitative QoL assessment can be performed by choosing from a large range of available tools. McHomey estimated in 2003 that almost 75 scales are used in oncology, and the choice of tool is fundamental to the study design and should be made according to the study’s objective, target population characteristics (head and neck cancer patients), and the psychometric properties of the scale [
11,
12]. There are two types of scales, generic and specific, and it is established that specific scales which address a certain disease/symptom/treatment are more sensitive to clinical variations and treatment effects than others are [
11,
12]. In addition, self-administered questionnaires are more sensitive. A validated scale meets the criteria of validity, reliability, and sensitivity. The validated scales specific to head and neck oncology, according to Heutte at al., are the QLQ-H&N35, a supplementary module to QLQ-C30, elaborated by the EORTC Group; Fact-H&N; University of Washington Questionnaire (UW-QOL); M. D. Anderson Symptom Inventory–Head & Neck (MDASI-HN); Head and Neck Performance Status Scale (PSS-HN); University of Michigan Head and Neck Specific Quality of Life Instrument and Head and Neck Cancer Inventory; Auckland Quality of Life Questionnaire (AQLQ). All these scales have either certain dimensions that are addressed or items specific to head and neck cancer treatments. The most frequently utilized and tested were: EORTC QLQ-H&N35, UWQOL, FACT-HN, and the University of Michigan Head and Neck Cancer Inventory [
11]. Certain scales address just a symptom or treatment for a range of symptoms. For example, scales specific to voice and speech include the Vocal Handicap Index (VHIVHI-10), Speech Handicap Index, University of Michigan Voice-related Quality of life, Voice Prosthesis Questionnaire, Self-Evaluation of Communication Experiences after Laryngectomy, Voice Activity Participation Profile, Voice symptom scale, Voice performance, Parole Handicap Index. There are also scales specific to mucositis and xerostomia; swallowing and mastication; shoulder pathology; dental and feeding pathology; fatigue; oral pain; anxiety, depression, and psychological impact; sexuality, sleep, and alcohol consumption; cognitive features; independence; support [
12].
Furthermore, finding the right instrument to assess a concept as large as the HRQoL is rather difficult, and some authors advocate that there cannot be a universal scale due to cultural and geopolitical differences. Even countries from the same continent can address pathologies with different angles, without deviating from the international guidelines, but with particularities due to their health system and socioeconomic development [
13]. In addition, there is no gold standard questionnaire, which is due to the volume and heterogeneity of QoL measures [
13]. Researchers should consider psychometric properties, research objectives, study design and pitfalls, and the benefits of combining different measures [
11,
13].
In our study, we used a validated Romanian EORTC QLQ-C30, version 3.0, developed by the European Organization for Research and Treatment of Cancer, Quality of Life Unit, Brussels, Belgium, in order to assess QoL at admission and at the 3-year follow-up (See
Supplementary Materials). This questionnaire was easy to complete, and patients declared in 89% of the cases that they thought this could be a tool to increase compliance. We found that the QLQ-H&N35 module in correlation with QLQ-C30 was, in most cases (56%), incorrectly completed, and patients declared that they found it tedious to answer so many questions.
The qualitative assessment is a new tool for physicians that allows them to see the disease in the context of the patient’s everyday life, with an open angle on physical data. The participant-observer experimental type is time-consuming, but it is a novel attitude in head and neck oncology, complementary to quantitative research [
10].
In general, after HNSSC treatment, the overall quality-of-life (QoL) scores reported were around 70, and the operating scale scores were around 80; fatigue was the most common general symptom, while problems related to speech, sexuality, and oral function (salivary, teeth, and mouth-opening problems) were the most common symptoms of head and neck damage [
14]. Some studies highlight factors such as tobacco use, psychological distress, and sex as the main determinants of long-term QoL. The correlation between tobacco use, psychological suffering, and QoL is complex and is mentioned by several authors [
15,
16]. As a result, interventions around smoking cessation and addressing psychological disorders could be direct actions for improving the system responsible for QoL. In addition, in the demographic factors of QoL impairment, some studies advocate that women are associated with lower indices [
14]. The demographic characteristics of our group were similar to those found in the literature, with a higher prevalence of HNSSC in men with a history of smoking and alcohol consumption and a median age of 58. Of 251 patients diagnosed in an advanced stage (IVa) and treated in one year (2019), only 38% (N = 95) survived; the group’s heterogeneity was due to the high percentage of patients with total laryngectomy (69%, N = 61). A small percentage of patients had previous oncological treatments—9% RT and 3% CHT—and were all from the hypopharyngeal group, without significant influence among the QOL scores.
The main concern of a patient who survives an HNSCC is the fear of recurrence, followed by dental problems, salivation, fatigue, and speech and eating disorders. In terms of addressability, the patient usually focuses on addressing the coordinating surgeon of the case before addressing the speech therapist and the oral rehabilitation team [
14]. Psychological distress is cited as the main determinant of long-term QoL, and the patient's age and gender significantly affect their needs and concerns [
14].
The study of patients’ quality of life requires the application of standardized questionnaires, which are validated by the medical community, and the most commonly used questionnaires are UW in the United States and EORTC H&N in Europe [
17,
18]. The results of a QoL meta-analysis of survivors at one year after treatment concluded that generally the overall QoL of patients deteriorated from pre-treatment to 1–6 months thereafter but gradually improved thereafter to 12 months [
17]. All studies analyzed reported a similar pattern during the examination period, although the change in the mean score between baseline and 12 months was not statistically significant (
p > 0.05) [
17]. Despite the general improvements in symptoms over time reported by many studies, xerostomia, changes in saliva consistency, and increased severity of fatigue influenced QoL in a statistically significant way at the one-year follow-up [
17]. Other symptoms, such as difficulties in managing physical appearance, speech, taste/smell, sexuality, or swallowing, were also reported by at least one study to be significantly worse at 12 months [
17]. Numerous studies showed that pain improved when compared with the pre-treatment period, and the anxiety score was also better than it was pre-treatment. Some studies showed that age was a determinant of QoL, but the data around the influence of sex on QoL are inconclusive. A multivariate analysis showed that the patient’s sex would have no influence on QoL [
17]. Psychological distress, the ability to eat in society, and concern about physical appearance were significantly associated with impaired QoL at the one-year follow-up. Specifically, depressive symptoms at baseline could also significantly predict overall QoL at 12 months [
17]. In our study, the QLQ scales seemed to provide better outcomes at the 3-year follow-up, but some of the symptoms, especially in the oral cavity and oropharyngeal groups, seemed to be worse at follow-up.
Regarding the QoL of patients with oral cancer, a longitudinal study that looked at 10-year-old survivors reported some improvement in physical appearance, chewing food, general condition, and anxiety but reported deterioration in swallowing. The study used the questionnaire developed by the University of Washington—University of Washington Quality of Life (UW-QOL) [
18]. A 10-year survival of up to 34% was reported, with factors influencing age, tumour stage, reconstructive surgery with free flaps, and the primary form of treatment (
p < 0.05). The affected results included appearance, mood, saliva, and shoulder function [
19]. In our group, the QoL scales after oral cavity cancer treatment had mean values around the average or below, with 41.0 for QoL and general health and well-being. The mean values reported were lower than those from admission: 53.3 for physical activity, 33.3 for role functioning, 25.0 for emotional functioning, 33.3 for cognitive functioning, and 33.3 for social functioning. Conversely, the symptom scale results were higher, meaning the results were worse than the admission ones, with an increase in fatigue, pain, insomnia, digestive symptoms, and financial difficulties.
In 2020, Ranta et al. published an extensive study on the quality of life of oropharyngeal cancer survivors at an average follow-up time of 11.79 years [
19]. Although the study model was a retrospective one, the results provide a topical overview of this type of cohort [
19]. A retrospective analysis of diagrams and patient responses to the questionnaire on quality of life created by the European Organization for Cancer Research and Treatment, the core module (EORTC QLQ-C30), the head and neck module (EORTC QLQ-H&N35) and M.D. Anderson Dysphagia Inventory (MDADI) questionnaires represented the study bases [
19]. Thus, they reported that, of the 263 survivors diagnosed and treated between 2000 and 2009, with a participation of 62.4% in the study (N = 164), most survivors reported a good QOL index [
19]. The median overall health status of EORTC QLQ-C30 was 75.00 (IQR = 31.25). The one-way treatment group had significantly better quality-of-life outcomes than the combined treatment group. Non-smokers and previous smokers had significantly better quality-of-life outcomes than patients who smoked at the time of diagnosis. Additionally, heavy alcohol consumption was associated with worse results [
19]. Patients with p16-positive cancer had significantly better QOL results than patients with p16-negative. Patients dependent on a percutaneous endoscopic gastrostomy tube (PEG) reported a significantly poorer quality of life than patients without a PEG tube [
19]. The conclusion of this national study was that long-term QOL in OPSCC survivors is generally good. According to the previous literature, the one-way treatment was superior to the combined treatment in terms of long-term QOL results and should be followed whenever possible [
19]. Similar data were reported from studies in Denmark, but there are very few studies with relevant results reported in developing countries. In our study, 3-year follow-ups reported mean values with better scores than the admission ones, though values were still around average—lower by 16.7 for QoL and general health and well-being, 13.3 points for physical activity, no change in points for role functioning, lower by 16.7 for emotional functioning, lower by 16.7 for cognitive functioning, and lower by 33.4 for social functioning. In the symptoms area, patients declared a lower fatigability; the same amount of pain; less dyspnoea, appetite loss, and constipation. However, they declared the same amount of financial difficulties. All patient survivors at the 3-year follow-up were patients with a transmandibular approach, without regional flap reconstruction. All reconstruction was made by local advancement flaps or with primary closure. Four patients had local complications: two had osteoradionecrosis, one rejected the titanium plate, and all of them developed fistulas.
The treatment of advanced laryngeal and hypopharyngeal cancer has undergone important changes in the sense that the transition from total laryngectomy (TL) to laryngeal preservation therapies is held due to the general perception that TL has a significant negative impact on a patient’s life. However, it has not yet been determined whether TL-related physical impairments translate into a health-related reduced quality of life (HRQoL). This paradigm shift began around the 1990s when the first of two large randomized clinical trials found that advanced laryngeal cancer could be treated with chemotherapy or radiation concomitant with an overall survival rate equivalent to that of TL with postoperative radiotherapy [
20]. However, laryngeal cancer is the only cancer with a decrease in survival in the United States in recent decades, where the relative 5-year survival rate from 1975 to 1989 was 66%, compared with a 63% survival rate between 2005 and 2011 [
19]. TL is a treatment that profoundly changes a patient’s quality of life, and people who have undergone such surgery are at risk of wound infection and necrosis, fistulas, dysphagia, voice problems, impaired breathing, and loss of smell [
20]. A systematic review of the literature comparing QoL in patients with advanced laryngeal cancer treated with organ preservation versus similar patients treated with surgery indicated that there are not enough studies of sufficient quality to draw any conclusions on this topic.
Despite the overall improvement in voice rehabilitation, the presence of a permanent tracheostomy after total laryngectomy has a negative impact on a patient’s postoperative quality of life [
20,
21]. There has therefore been an increasing emphasis on laryngeal conservation in the development of new treatment strategies for patients with laryngeal cancer. Rather than focusing on the conservation of the larynx as an organ, the preservation of its function is the ultimate challenge in these procedures [
21].
In our study, the VP group related a higher mean value for functional scales and a lower one in comparison with admission—QoL and general health and well-being with 33.3 points, physical activity with 26.7 points, no change in points for role functioning, emotional functioning with 58.3 points, and social functioning with 33.3 points. On the symptom scales, patients declared less fatigue (lower with 44.4 points), no nausea and vomiting, less pain (lower with 50 points), some degree of dyspnoea (33.3), the same degree of insomnia, a higher percentage of constipation, and the same degree of financial difficulties (
Figure 1). Patients without VP declared a lower QoL and general well-being than those in the VP group but higher than their admission scores and further lower scores on functional scales than those in the VP group. The patients without VP declared mean values for the symptom scales lower than those in the VP group, with only 33 points for insomnia, 66 for constipation, and 50 for financial difficulties.
What may significantly change the QoL score is the currently very good quality vocal rehabilitation. A review of the literature which included studies encompassing 1085 laryngectomy patients undergoing voice rehabilitation, of which 869 (80.1%) were treated with voice prosthesis (VTE) while 216 (19.9%) were treated with oesophageal speech (EV), indicated that the cumulative VHI (Voice Handicap Index) results showed a significantly better score for the VTE (tracheoesophageal voice) group than for the EV (oesophageal voice) group (31.93 ± 12, 11 compared with 35.39 ± 20.6;
p = 0.003). Since there was no significant difference recorded in VrQoL, the study claimed that VTE and EV are both effective procedures in voice rehabilitation after laryngectomy [
21]. Although VTE allows for significantly better speech performance, it does not necessarily correlate to high VrQoL [
21]. However, VTE is the current gold standard in postlaryngectomy vocal rehabilitation [
21].
Our study has some limitations: A lack of a statistical correlation, a focus on descriptive analysis, and small groups. Further studies should take into consideration a timeline with a shorter follow-up period, which implies prospective studies. Additionally, multi-centre studies could give an adequate overview of QoL in developing countries.