Accepted 24 October 2005 Published online 23 May 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: /hed.20389

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ORIGINAL ARTICLE COMPARISON OF THE DOMAINS OF ANXIETY AND MOOD OF THE UNIVERSITY OF WASHINGTON HEAD AND NECK CANCER QUESTIONNAIRE (UW-QOL V4) WITH THE CES-D AND HADS Simon N. Rogers, FDS, RCS, FRCS, MD, 1 Bijaya Rajlawat, 2 Janaki Goru, 2 Derek Lowe, MSc, CStat, 1 Gerry M. Humphris, PhD, MClin Psychol, C Psychol 3 1 Regional Maxillofacial Unit, University Hospital Aintree, Liverpool, Regional Maxillofacial Unit, University Hospital Aintree, Fazakerley, Liverpool L9 1AL UK. E-mail: snrogers@doctors.org.uk 2 Liverpool University, United Kingdom 3 Bute Medical School, University of St Andrews, Fife, Scotland, United Kingdom Accepted 24 October 2005 Published online 23 May 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20389 Abstract: Background. Version 4 of the University of Washington Head and Neck Cancer Questionnaire (UW-QOLv4) includes items on mood and anxiety. The aim of this study was to compare the responses to these single items with the Centre for Epidemiology Studies Depression Scale (CES-D) and the Hospital Anxiety Depression Scale (HADS). Methods. A cross-sectional postal survey was undertaken in April 2003. The survey was composed of all patients treated for oral and oropharyngeal squamous cell carcinoma between 1992 and 2002 who were alive and disease free. Results. We distributed 306 questionnaires; there were 197 replies (65%) from 110 male and 87 female patients. Most patients reported relatively little depression, with 170 of 190 (89%) reporting a HADS depression score of less than 11. Similarly, most patients were not anxious, with 158 of 183 (86%) reporting a HADS anxiety score of less than 11. UW-QOL mood, UW-QOL anxiety, HADS anxiety, HADS depression, and CES-D scores were all moderately intercorrelated (Spearman correlations from 0.39 0.68 ignoring the signs, all p <.001). The UW- Correspondence to: S. N. Rogers Ethical approval was given for this study by the South Sefton Ethical Committee. VC 2006 Wiley Periodicals, Inc. QOL mood correlated with the scores and case-ness categories of the HADS depression and CES-D scales, whereas the UW-QOL anxiety correlated with the scores and case-ness of the HADS anxiety. Conclusions. Questions on mood and anxiety can help identify significant psychological morbidity, taking a score of less than 75 for UW-QOL mood and less than 70 for UW-QOL anxiety. This could be used to trigger formal psychological assessment and with a view to possible therapeutic intervention. VC 2006 Wiley Periodicals, Inc. Head Neck 28: 697 704, 2006 Keywords: health-related quality of life; head and neck cancer; mood; anxiety; UW-QOL, HADS, CES-D Patients can endure many difficulties and debilitating changes after treatment for oral and oropharyngeal cancer such as in speech, swallowing, chewing, and appearance. 1 These limitations create problems for social interaction and emotional expression. 2 4 Not surprisingly, several studies have reported a high incidence of psychological distress in this patient population. 5 9 Depression is also common 10,11 along with worry, anxiety, mood disorders, and fatigue. 12 Psychological as- Anxiety and Mood in Quality of Life Questionnaires HEAD & NECK DOI 10.1002/hed August 2006 697

pects are an important component of healthrelated quality of life (HRQOL). The recognition of psychological problems is useful because these conditions are potentially treatable and intervention can ameliorate dysfunction and improve HRQOL. Several head and neck specific cancer HRQOL questionnaires are available. 13,14 The University of Washington Head and Neck Cancer Questionnaire (UW-QOL) was the most popular in a national survey of active UK consultant clinicians on the mailing list of the British Association of Head and Neck Oncologists. 15 Because of its simplicity and multidisciplinary acceptance, the UW-QOL is being considered as a national HRQOL outcomes tool in the UK. The UW-QOL has evolved since first being published in 1993. 16 It is only in the most recent version (version 4) that psychological domains were included using a question on mood (five response categories) and another on anxiety (four response categories). 17 Mood was chosen as an appropriate domain to capture depressive morbidity. Previous work by Allen et al 18 has shown that depressed mood in the last month had the strongest item-total correlation to a brief depression assessment scale developed for elderly people in medical and surgical inpatients. Anxiety was also selected as an essential additional domain describing the emotional component. Anxiety may independently exist or co-vary with depressed mood. 19 The mood and anxiety domains of the UW- QOLv4 have been shown to correlate significantly with the emotional functioning domains of the EORTC 30 questionnaire. 17 Although these correlations exist, the interpretation of these domain scores would be greatly assisted by confirming the predicted associations with other frequently used scales with good evidence for detecting psychological distress. This comparison would help define clinical cutoffs in domain scores and determine the score that may reflect significant psychological distress or morbidity. Hence, the aim of this study was to acquire further evidence for the validity of these questions by comparing them with the Centre for Epidemiology Studies Depression Scale (CES-D) and the Hospital Anxiety Depression Scale (HADS). PATIENTS AND METHODS Patients. The study population was composed of consecutive patients undergoing surgery for previously untreated oral and oropharyngeal squamous cell carcinoma presenting to the Regional Maxillofacial Unit Liverpool from 1 January 1992 to 31 December 2002. A cross-sectional postal survey was undertaken in April 2003 of all patients who were alive and disease free. Measures. The UW-QOL questionnaire 17 covers 12 domains: pain, appearance, activity, recreation, swallowing, chewing, speech, shoulder function, taste, saliva, mood, and anxiety. It also has a question that asks patients to choose up to three domains of most importance to them and two global questions about their health-related and overall quality of life. Mood is measured on a 5- point and anxiety on a 4-point Likert scale. Each question is scaled from 0 (worst) to 100 (best), according to the hierarchy of response. The HADS questionnaire was designed to detect mild degrees of mood disorder, anxiety, and depression in inpatients. 20 The Anxiety and Depression subscales both are composed of seven questions rated from 0 to 3, depending on the probability of the psychological problem described. These scales can be categorized as normal (0 7), possibly significant (8 10), and probably significant (11 21). 21 The questionnaire was validated in nonhospital settings and has been used in several non psychiatry-based studies assessing the impact of conditions such as oncology that might affect mental health. 5,22,23 The CES-D is a validated 20-item self-report measure. 24 The main components of depressive symptoms (depressed mood, feelings of guilt and worthlessness, feelings of helplessness and hopelessness, psychomotor retardation, loss of appetite, and sleep disturbance) were originally identified from clinical literature and statistical tools such as factor analysis. Each item includes four response categories, scored from 0 to 3. The CES- D score is the sum of the 20 items, ranging from 0 to 60. A typographical error omitted the last question I could not get going. Overall scores were therefore scaled by a multiplying factor of 20 divided by the number of items completed (minimum of 15) to obtain a score from 0 to 60. A score of 16 or more has been used extensively as the cutoff point for high depressive symptoms on this scale. 25,26 Statistical Methods. Presentation of results was primarily descriptive, making use of percentages, means, and standard errors. Tests of significance (Mann Whitney or Spearman correlation as appropriate) were used to investigate the association 698 Anxiety and Mood in Quality of Life Questionnaires HEAD & NECK DOI 10.1002/hed August 2006

Table 1. Characteristics of the 1992 2002 cohort of patients who were alive and disease free in April 2003. Characteristic Responders (n ¼ 197) No. (%) Nonresponders (n ¼ 109) Sex Male 110 (56) 68 (62) Age at operation, y < 55 59 (30) 41 (38) 55 64 66 (34) 26 (24) 65 74 47 (24) 29 (27) 75 25 (13) 13 (12) Tumor site Oral cavity 175 (89) 97 (89) Oropharynx 19 (10) 12 (11) Maxillary sinus 3 (2) Tumor size < 2 cm 61 (31) 30 (28) 2 3 cm 86 (44) 51 (47) 4 5 cm 30 (15) 19 (17) > 6 cm 11 (6) 7 (6) Unknown 9 (5) 2 (2) Clinical T classification T1 54 (27) 25 (23) T2 67 (34) 40 (37) T3 16 (8) 11 (10) T4 46 (23) 23 (21) Tis 13 (7) 9 (8) TX 1 (0.5) 1 (1) Surgery Flap 136 (69) 78 (72) Laser/primary closure/ssg 61 (31) 31 (28) Adjuvant radiotherapy 63 (32) 36 (33) between patient clinical features and scores on the UW-QOL, HADS, and CES-D. The level of statistical significance was taken as p <.05. Confirmatory factor analysis was conducted using AMOS TM v5, specifying the two HADS subscales as the latent variables of depression and anxiety. 27 The two UW-QOL items: anxiety and mood were modeled to load on the respective HADS subscales. Standard measures of fit were inspected to determine whether the UW-QOL items could be considered as indicators of each latent variable. 28 RESULTS From 1992 to 2002, there were 577 previously untreated patients with head and neck squamous cell carcinoma, and by April 2003, 306 were known to be alive and without recurrent disease. Of these, survey questionnaires were returned from 65% (197 of 306). Patient characteristics are summarized in Table 1. No obvious response biases were found in regard to clinical features, although time from operation was less for responders (median, 41 months; interquartile range [IQR], 24 76) than for nonresponders (median, 56 months; IQR, 28 85). Of the responders, 49% said their mood was excellent and unaffected by their cancer, and 46% said they were not anxious about their cancer (Table 2), whereas 37% (n ¼ 71) gave both of these responses. At the other extreme, 9% (n ¼ 18) were somewhat or extremely depressed and 11% (n ¼ 22) anxious or very anxious, with 5% (n ¼ 10) being both. On the HADS, 11% were probably depressed with a score of 11 or more, whereas 14% were probably anxious, with 6% (n ¼ 11) being both. On the CES-D, 27% scored 16 or more (ie, greater than the Table 2. Responses to the mood and anxiety domains of the University of Washington Quality of Life Questionnaire (UW-QOL), the Hospital Anxiety and Depression Scale (HADS), and the Centre for Epidemiologic Studies Depression scale (CES-D). Questionnaire score Score No. of patients (%) UW-QOL Mood (N ¼ 194) My mood is excellent and unaffected 100 95 (49) by my cancer My mood is generally good and 75 61 (31) only occasionally affected by my cancer I am neither in a good mood nor 50 20 (10) depressed I am somewhat depressed 25 17 (9) I am extremely depressed 0 1 (0.5) UW-QOL Anxiety (N ¼ 194) I am not anxious 100 89 (46) I am a little anxious 70 83 (43) I am anxious about 30 21 (11) my cancer I am very anxious 0 1 (0.5) HADS Anxiety (N ¼ 183) Normal 0 7 127 (69) Borderline abnormal 8 10 31 (17) Abnormal 11 21 25 (14) HADS Depression (N ¼ 190) Normal 0 7 154 (81) Borderline abnormal 8 10 16 (8) Abnormal 11 21 20 (11) CES-Depression (N ¼ 181) <10 93 (52) 10 15 40 (22) 16 24 25 (14) 25þ 23 (13) Abbreviations: UW-QOL, University of Washington Quality of Life Questionnaire; HADS, Hospital Anxiety and Depression scale; CES, Centre for Epidemiologic Studies Depression scale. Anxiety and Mood in Quality of Life Questionnaires HEAD & NECK DOI 10.1002/hed August 2006 699

Table 3. Association of UW-QOL mood, HADS, and CES-D scores. UW-QOL mood My mood is excellent and unaffected by my cancer (100) My mood is generally good and only occasionally affected by my cancer (75) I am neither in a good mood nor depressed (50) I am somewhat depressed about my cancer (25) I am extremely depressed about my cancer (0) HADS depression Normal Borderline Abnormal 0 7 8 10 11 21 Mean (SE) 89 1 3 1.7 (0.3) 48 4 6 4.8 (0.4) 10 6 3 6.8 (0.9) 5 4 7 9.3 (0.9) 1 19 ( ) UW-QOL mood < 16 16 24 25þ Mean (SE) My mood is excellent and unaffected 86 1 3 6.6 (0.7) by my cancer (100) My mood is generally good and only occasionally 35 14 7 13.5 (1.2) affected by my cancer (75) I am neither in a good mood nor depressed 8 4 6 19.1 (2.4) (50) I am somewhat depressed (25) 4 4 6 23.6 (2.9) I am extremely depressed (0) 1 48.4 ( ) Abbreviations: UW-QOL, University of Washington Quality of Life Questionnaire; HADS, Hospital Anxiety and Depression Scale; CES-D, Centre for Epidemiologic Studies Depression scale. CES-D conventional cutoff point for high depressive symptoms), with 13% scoring 25 or more. UW-QOL mood, UW-QOL anxiety, HADS anxiety, HADS depression, and CES-D scores were all moderately intercorrelated (Spearman correlations from 0.39 0.68 ignoring the signs, all p <.001). UW-QOL mood correlated with HADS anxiety score (0.65) as strongly as with HADS depression score (0.66) and CES-D score (0.56). This was evident also from correlations of UW-QOL mood with the seven HADS anxiety items (median, 0.50; IQR, 0.36 0.64), the seven HADS depression items (median, 0.50; IQR, 0.30 0.65), and the 19 CES-D items (median, 0.39; IQR, 0.28 0.48). UW- QOL anxiety correlated more strongly with HADS anxiety (0.54) than with HADS mood (0.39) and CES-D (0.40), again also evident from correlations of UW-QOL anxiety with the seven HADS anxiety items (median, 0.46; IQR, 0.32 0.55), the seven HADS depression items (median, 0.29; IQR, 0.19 0.42), and the 19 CES-D items (median, 0.31; IQR, 0.20 0.38). CES-D total scores correlated as strongly with HADS anxiety scores (0.68) as with HADS depression scores (0.68). Through confirmatory factor analyses, we tested whether the UW-QOL mood and anxiety items loaded on the predicted subscales of the HADS, that is the anxiety item loaded on the HADS anxiety subscale and the mood item on the HADS depression subscale. This model fitted reasonably well (chi square ¼ 202.7, df ¼ 102). However, allowing mood to load on the HADS anxiety scale as well as on the HADS depression scale improved the fit (chi square reduction of 3.9, df ¼ 1, p ¼.048), suggesting that UW-QOL mood assesses aspects of both depression and anxiety. Tables 3 and 4 show how UW-QOL mood correlated with the scores and case-ness categories of the HADS depression scale. Of 17 patients who were either somewhat or extremely depressed about their cancer, 47% (8 of 17) scored 11 or more on the HADS depression scale compared with 7% (12 of 170) of other patients (Table 3). This group of 17 patients, however, only included 40% (8 of 20) of all patients scoring 11 or more on the HADS scale. Thus, taking a score of 50 as a screening cutoff for UW-QOLmoodgaveapositivecasepredictivevalue of 47% and a sensitivity of 40% (Table 4). Taking 75 and 100 as cutoffs for mood improved sensitivity to 55% and 85%, respectively, but positive case predictiveness fell to 31% and 18%. A similar story emerged for CES-D case-ness (Tables 3 and 4). Tables 5 and 6 show how UW-QOL anxiety correlated with the scores and case-ness categories 700 Anxiety and Mood in Quality of Life Questionnaires HEAD & NECK DOI 10.1002/hed August 2006

Table 4. Equating UW-QOL mood score with HADS depression and CES-D case-ness. Data in this table were derived from Table 3. HADS depression case-ness ¼ 11 21 score Sensitivity Specificity PPV NPV Cut-off for UW-QOL mood n (%) n (%) n (%) n (%) < 50 vs 50þ 8/20 (40) 158/167 (95) 8/17 (47) 158/170 (93) < 75 vs 75þ 11/20 (55) 142/167 (85) 11/36 (31) 142/151 (94) < 100 vs 100 17/20 (85) 90/167 (54) 17/94 (18) 90/93 (97) CES-D case-ness ¼ 16 60 score Sensitivity Specificity PPV NPV Cut-off for UW-QOL Mood n (%) n (%) n (%) n (%) < 50 vs 50þ 11/46 (24) 129/133 (97) 11/15 (73) 129/164 (79) < 75 vs 75þ 21/46 (46) 121/133 (91) 21/33 (64) 121/146 (83) < 100 vs 100 42/46 (91) 86/133 (65) 42/89 (47) 86/90 (96) Abbreviations: UW-QOL, University of Washington Quality of Life Questionnaire; HADS, Hospital Anxiety and Depression Scale; CES-D, Centre for Epidemiologic Studies Depression scale; PPV, positive (case) predictive value; NPV, negative (no case) predictive value. of the HADS. There is a clear increase in HADS anxiety scores as UW-QOL anxiety worsens. There are only two practical cutoffs possible for UW-QOL anxiety, at 70 and 100. The sensitivity of the 100 cutoff (79%) was better than at 70 (50%), but the ability to predict case-ness was substantially worse at 20%, from 60%. Evidence (not presented and available on request) at p <.05 was found from both the UW-QOL mood and HADS depression scales that patients with larger tumors, later staging, flap surgery, and adjuvant radiotherapy had worse levels of mood/depression. Evidence was also found from both the UW-QOL anxiety and HADS anxiety scales that female patients were more anxious. DISCUSSION Psychological distress after head and neck cancer is common. 5,29,30 Not only is psychological distress treatable, but it may also have an impact on patient compliance and medical outcome. 31 In our cross-sectional survey, a notable minority of patients were anxious or depressed after primary surgery with or without adjuvant radiotherapy for oral and oropharyngeal squamous cell carcinoma. Threescaleswereused,theUW-QOLv4,HADS,and CES D, and approximately one in 10 patients were either probably anxious or depressed. A larger proportion of women were anxious, whereas mood seemed to be influenced by issues relating to tumor stage and the need for radiotherapy. Women have been previously recognized as tending to be more anxious. 5,32,33 In our study, the relatively low level of psychological morbidity reflects the cross-sectional surgery of a patient cohort predominately 3 to 4 years after surgery. The cohort represents survivors. Furthermore, patients with recurrence were excluded from this study. It is also possible that those patients with psychological distress were least likely to return the questionnaires and are, therefore, likely to be underrepresented. In this cross-sectional study, pretreatment psychological distress was not captured. Radford et al 34 have, however, published longitudinal data using the UW-QOLv4. The pretreatment anxiety Table 5. Association of UW-QOL anxiety and HADS scores. HADS anxiety Normal Borderline Abnormal UW-QOL anxiety 0 7 8 10 11 21 Mean (SE) I am not anxious (100) 74 7 5 3.4 (0.4) I am a little anxious (70) 47 21 7 6.4 (0.4) I am anxious (30) 5 3 11 10.7 (0.8) I am very anxious (0) 1 18.0 ( ) Abbreviations: UW-QOL, University of Washington Quality of Life Questionnaire; HADS, Hospital Anxiety and Depression Scale. Anxiety and Mood in Quality of Life Questionnaires HEAD & NECK DOI 10.1002/hed August 2006 701

Table 6. Equating UW-QOL anxiety score with HADS anxiety case-ness. Data in this table were derived from Table 5. HADS anxiety case-ness ¼ 11 21 score Sensitivity Specificity PPV NPV Cut-off for UW-QOL anxiety n (%) n (%) n (%) n (%) <70 vs 70þ 12/24 (50) 149/157 (95) 12/20 (60) 149/161 (93) <100 vs 100 19/24 (79) 81/157 (52) 19/95 (20) 81/86 (94) Abbreviations: UW-QOL, University of Washington Quality of Life Questionnaire; HADS, Hospital Anxiety and Depression Scale; PPV, positive (case) predictive value; NPV, negative (no case) predictive value. domain was ranked most important, equal with swallowing. Mood was ranked sixth out of the 12 domains. The only domains to improve from baseline to 6 months were anxiety, pain, and mood. At 6 months, anxiety was ranked eighth and mood 11th in frequency of importance. One of the main purposes of this study was to test the correlation between UW-QOLv4 and HADS and UW-QOL and CES-D. It seems from Spearman s correlations and factor analysis that the UW-QOL mood assesses aspects of both depression and anxiety, whereas the UW-QOL anxiety largely seems to restrict itself to anxiety. Depressive and anxiety disorders typically co-occur, approximately 40% to 75% of the time. 19,35 Measures that successfullyseparatethetwoconstructswithlittleoverlap may suffer by showing poor face validity. Hence, single-item questions to assess depression and anxiety are likely to be significantly associated. Another aim of this study was to gain an insight as to the clinical meaning for UW-QOL anxiety and mood scores in predicting psychological morbidity. It is appreciated that a full psychiatric interview would be necessary on every patient to fully test this hypothesis, but this is impracticable. The HADS is now accepted as a reasonable screening tool but is not able to be sufficiently robust to give a clinical classification. We found that the UW-QOL mood correlated with the scores and case-ness categories of the HADS depression and CES-D scales, whereas the UW- QOL anxiety correlated with the scores and caseness of the HADS anxiety. This strict categorization of anxiety and depression at the cutoff of 11 has been shown to have clinical meaning, but as with Hammerlid et al, 5 we have also considered the eight to 10 band as possible, whereas the greater than 10 band is referred to as probable. For the CES-D, a score of 16 or more has been used extensively as the cutoff point for high depressive symptoms, 25,26 although a higher cutoff has been considered. 36,37 Our study was compromised by the unintentional absence of the 20th item. This, thankfully, did not negate the value of using this measure, and although the CES-D did not demonstrate the relationships as well as the HADS or UW-QOL measures, we accept that the measure was not complete and inferences are limited. A recent study by Katz et al 9 compared the HADS, CES-D, and the Beck Depression Scale with results from a clinical interview with 60 patients, all of whom were ambulatory and had been treated with radiotherapy. Their results were interesting in that they reported the prevalence of depression to be 20%. This rate was considerably higher than our findings. The patients involved in the Katz study were all investigated at the 1-month point after radiation treatment. It is known that this is a key period when depression rates tend to be high. 5 The Katz study is helpful because it explores the relationships between a number of self-report depression instruments and a recognized clinical interview. Additional work to determine the accuracy of the UW-QOL and the HADS, for example with reference to a clinical interview over the time course after treatment, is an important next step. From Table 4, a cutoff less than 50 for mood and from Table 6 less than 70 for anxiety would identify a group of patients of whom at least half would have case-ness on the HADS. Having a cutoff of less than 75 for mood would double the number of patients of which only a third have case-ness, but less than a half will have normal (0 7) values. Having a cutoff at less than 100 for anxiety would give four to five times as many patients, but the case-ness is down to 20%. Another way of considering these data is that, in this cohort, if the cut off for mood were less than 75, 19% of patients would be referred for further assessment; if the cutoff were less than 50, only 9% would be referred. For anxiety, the cutoff seems more distinct at less than 70, and taking this value, 11% would be sent for further evaluation. To avoid referral of many patients who do not have problems, the lower value of UW-QOL is favored; however, it is possible that patients with 702 Anxiety and Mood in Quality of Life Questionnaires HEAD & NECK DOI 10.1002/hed August 2006

anxiety and depression states could be missed. Also, pretreatment levels of UW-QOL, particularly for anxiety, will be lower, and taking the lower value will help target those most distressed. These issues of appropriate cutoff values need further evaluation, and a longitudinal study from baseline would be of help to confirm the clinical relevance of the proposed cutoffs. The importance of addressing psychological needs has wide recognition. Not only is psychological distress treatable, it may also have an impact on patient compliance and medical outcome. 31 The next phase of this clinical research project is to perform a longitudinal study to explore whether the UW-QOL domains scores can identify at-risk patients and trigger appropriate intervention. CONCLUSION Ample evidence suggests the significant presence of psychological distress in patients who have been treated for head and neck cancer. Psychological interventions have a role in reducing this distress. 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