Introduction 1 2 2 5 6 7 7 5 8 9 11 12 15 16 17 19 The primary objective of the present study is to assess pretreatment HRQOL and functional status in relation to tumor site, tumor classification and comorbidity, in a well-defined group of patients with advanced oral and oropharyngeal cancer. Patients and methods Patients Between January 1998 and December 2001, 92 consecutive patients diagnosed with stage II-IV oral or oropharyngeal squamous cell carcinomas were asked to participate in the study. The planned treatment was composite resection with microvascular soft tissue transfer (i.e., radial forearm free flap) for the reconstruction of surgical defects, and radiotherapy on indication. Exclusion criteria were age greater than 75 years, serious cognitive impairment and lack of basic fluency in the Dutch language. Twelve patients declined to participate, resulting in a final sample of 80 patients (response rate = 87%). All patients were treated at the Department of Otolaryngology/Head and Neck Surgery of the VU University Medical Center, Amsterdam, The Netherlands. Data collection and study measures All data were collected prior to the start of treatment, including sociodemographics (age and gender), disease stage, comorbidity, HRQOL, and functional status. Comorbidity was assessed dichotomously (yes or no) by review of medical records and on the basis of self-report, and was noted if one or more relevant medical ailments accompanied the primary medical illness. The comorbid conditions were cardiovascular, respiratory, gastro-intestinal, renal, endocrine, neurological, and immunological disorders, previous malignancy and considerable weight loss or alcohol abuse. For example, cardiovascular problems such as a myocardial infarct or hypertension, respiratory problems such as restrictive lung disease or COPD, or endocrine disorders such as diabetes mellitus with insulin usage were defined as relevant comorbid conditions. 20 21 22 8 Speech and oral functional status Speech analyses were performed according to a standardized speech assessment protocol. Speech recordings of a read aloud text were performed in a sound-treated room and digitized using Cool Edit PRO 1.2 (Adobe Systems Incorporated, San Jose, CA, USA) with 22 kHz sample frequency and 16 bit resolution. Recording level was adjusted for each speaker to optimize signal-to-noise ratio. All recordings were made with a mouth-to-microphone distance of 30 cm. A computer program was developed to perform blinded randomized speech evaluation and to score overall intelligibility, and quality of articulation and nasal resonance. Overall intelligibility was assessed on a 10-point scale ranging from poor to excellent by two trained speech therapists. Scores below six were defined as insufficient intelligibility (according to the Dutch educational system). To obtain more insight into the cause of decreased intelligibility, evaluation of the quality of articulation and nasal resonance was performed by the same two speech therapists on a 4-point scale ranging from deviant (score 1–3) to normal (score 4). Speech rate was measured by calculating words per minute on a read aloud standardized text. 23 Statistical analyses t t r P Results Sample description 1 2 P Table 1 Characteristics of 80 patients included in this study Age (years)  Range 23–74   Mean 58  n Gender  Male 47 (59)  Female 33 (41) General condition  Comorbidity 48 (60)  No comorbidity 32 (40) Tumour site  Oral cavity 38 (47)  Oropharynx 42 (53) T  2  35 (44)  3  42 (52)  4  3 (4) N  0 24 (30)  1 16 (19)  2a 2 (3)  2b 30 (38)  2c 6 (7)  3  2 (3) Health-related quality of life P P P P P P P P P P P P P P P P P P P P P P P 2 P P P P P P P P P P P P Table 2 EORTC QLQ-C30 and QLQ-H&N35 scores for comorbidity  Comorbidity No Yes  n n P EORTC QLQ-C30  Physical functioning 95.0 (12.4) 81.7 (21.4) 0.002  Role functioning 85.4 (18.3) 79.2 (24.9) 0.228  Cognitive functioning 89.6 (18.3) 87.2 (19.2) 0.574  Emotional functioning 69.5 (23.4) 72.2 (24.6) 0.626  Social functioning 93.2 (13.3) 88.5 (21.5) 0.275  Global quality of life 82.6 (19.6) 71.5 (19.7) 0.016  Fatigue 13.9 (20.0) 26.9 (24.1) 0.014  Emesis 1.6 (4.9) 1.4 (4.7) 0.874  Pain 22.4 (25.3) 37.8 (31.8) 0.024  Dyspnea 6.3 (19.7) 10.4 (18.4) 0.338  Insomnia 36.5 (36.3) 31.3 (39.1) 0.550  Appetite loss 7.3 (20.3) 18.7 (31.4) 0.072  Constipation 5.2 (20.9) 18.7 (32.9) 0.042  Diarrhea 1.0 (5.9) 8.3 (16.1) 0.017  Financial impact 2.1 (8.2) 7.6 (20.9) 0.157 EORTC QLQ-H&N35  Pain 27.1 (17.6) 41.5 (25.5) 0.007  Swallowing 14.6 (22.6) 24.1 (22.6) 0.068  Senses  6.3 (14.5) 8.7 (21.5) 0.577  Speech  9.4 (14.1) 13.0 (17.5) 0.336  Social eating 14.6 (25.3) 27.4 (27.1) 0.036  Social contact 3.1 (7.0) 3.7 (6.1) 0.674  Sexuality 16.1 (24.9) 16.3 (27.6) 0.981  Teeth 13.5 (26.6) 30.6 (38.8) 0.034  Opening mouth 7.3 (20.3) 25.7 (37.2) 0.013  Dry mouth 15.6 (26.8) 22.2 (28.6) 0.303  Sticky saliva 12.5 (29.0) 21.5 (31.1) 0.196  Coughing 6.3 (13.2) 14.6 (21.6) 0.055  Feeling ill 0 (0) 9.7 (18.1) 0.003  % Yes % Yes  Pain medication 50.0 75.0 0.022 Speech and oral functional status 3 P P P P P P P P P P P P P P Table 3 Functional status tests for tumour site, tumour stage and comorbidity  Tumour site Tumour stage Comorbidity Oral cavity Oropharynx  T2 T3–T4  No Yes  n n P n n P n n P Speech  Intelligibility   (0–10) 6.0 (1.3) 6.7 (1.0) 0.015 6.8 (1.0) 6.0 (1.2) 0.011 6.6 (1.0) 6.2 (1.3) 0.132  Articulation   (0–4) 3.4 (0.8) 3.7 (0.6) 0.039 3.8 (0.4) 3.3 (0.8) 0.003 3.8 (0.4) 3.4 (0.8) 0.043  Nasality   (0–4) 3.6 (0.6) 3.8 (0.4) 0.040 3.8 (0.4) 3.7 (0.6) 0.911 3.7 (0.4) 3.7 (0.5) 0.771  n n  n n  n n   Rate   Words per minute 183 (31.6) 182 (38.5) 0.988 189 (33.8) 178 (35.8) 0.201 189 (31.4) 179 (38.1) 0.233  n n  n n  n n  Oral functions  Mobility   Tongue (0–100) 82.3 (20.0) 96.4 (5.4) 0.000 96.0 (5.8) 84.8 (19.3) 0.001 93.9 (9.9) 89.9 (14.4) 0.209   Lip (0–100) 87.4 (5.7) 99.7 (0.9) 0.009 99.4 (2.0) 98.0 (5.1) 0.140 99.3 (2.2) 98.5 (3.9) 0.239   Diadoch (0–100) 87.4 (20.7) 97.2 (6.1) 0.004 97.5 (5.0) 88.7 (19.6) 0.012 97.4 (5.1) 91.5 (15.4) 0.026  Strength   Tongue (0–0.5) 0.2 (0.2) 0.4 (0.2) 0.001 0.4 (0.2) 0.3 (0.2) 0.021 0.4 (0.2) 0.2 (0.2) 0.045   Lip (0–0.5) 0.3 (0.1) 0.4 (0.2) 0.328 0.4 (0.2) 0.3 (0.1) 0.018 0.4 (0.2) 0.3 (0.1) 0.370 Correlations between self-report and observer rated data P r r 4 P r r r r Table 4 Correlations between functional status tests and QLQ-C30 global quality of life scale/QLQ-H&N35 speech problems  Scales QLQ-C30 global quality of life QLQ-H&N35 speech problems r n P r n P Speech  Intelligibility 0.411 0.000 −0.285 0.013  Articulation 0.355 0.002 −0.242 0.035  Nasality 0.152 0.190 −0.270 0.019  n  n   Rate 0.129 0.267 −0.142 0.221  n  n  Oral functions  Mobility   Tongue 0.078 0.490 −0.188 0.095   Lip 0.157 0.164 −0.176 0.119   Diadochokinesis 0.109 0.337 −0.280 0.012  Strength   Tongue 0.188 0.095 −0.175 0.121   Lip 0.056 0.624 −0.049 0.665 Discussion 9 15 14 24 25 26 29 17 30 19 4 9 11 2 14 13 14 In conclusion, we observed compromised HRQOL and functional deficits among patients with advanced oral and oropharyngeal cancer before the start of treatment. In addition to the impact of tumor site and classification, comorbidity proved to have a major impact on HRQOL and functional status. Prospective studies are needed to obtain insight into the relation between pretreatment HRQOL and functional status and outcome after treatment, and the relationship between changes in HRQOL and functioning over time and tumor site, tumor classification, and comorbid conditions.