Psychosocial factors and patient and healthcare delays in large (class T3-T4) oral, oropharyngeal, and laryngeal carcinomas.

BACKGROUND: Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer. PATIENTS AND METHODS: We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period. RESULTS: We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers. CONCLUSIONS: Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice.

Hypopharyngeal carcinoma in Finland from 2005 to 2014: outcome remains poor after major changes in treatment.

PURPOSE: Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. METHODS: We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. RESULTS: The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. CONCLUSIONS: The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.

Timing and frequency of oropharyngeal squamous cell carcinoma recurrences after treatment with curative intent.

BACKGROUND: The increasing number of patients under surveillance after treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC) places a great burden on healthcare providers. AIMS/OBJECTIVES: The aim of this study was to explore OPSCC recurrences in a long follow-up period: their site, frequency and timepoint after primary treatment, treatment and outcome. The secondary aim was to investigate if the recurrences are diagnosed on routine follow-up visits, and if the p16 status will have an effect on the pattern of recurrences. MATERIAL AND METHODS: We analyzed recurrences within a 10-year follow-up period after completed curatively intended treatment among OPSCC patients in Finland treated between 2000 and 2009. Patient-, tumor-, treatment- and follow-up -related parameters were investigated. RESULTS: Out of 495 patients with no residual tumor during the first six months, 71 (14%) were diagnosed with a recurrence, of which 47 were locoregional and 28 were treated with curative intent. Of the recurrences, 86% were diagnosed during the first 36 months after primary treatment. Only ten recurrences appeared after 36 months. The median OS after recurrence was 10.9 months. CONCLUSIONS AND SIGNIFICANCE: Routine follow-up longer than three years after treatment seems not to be effective in terms of detecting OPSCC recurrences.

Patient and health care delays in large (class T3-T4) oral, oropharyngeal, and laryngeal carcinomas.

BACKGROUND: Head and neck cancers (HNCs) are often diagnosed at an advanced stage. We investigated the lengths and factors associated with patient, primary health care (PHC), and specialist care (SC) delays in T3-T4 oral, oropharyngeal, and laryngeal cancer. METHODS: A nationwide prospective questionnaire-based study (n = 203) with the 3-year long data collection period. RESULTS: The median patient, PHC and SC delays were 58, 13, and 43 days, respectively. Lower level of education, heavy alcohol use, hoarseness, difficulties breathing, and eventual palliative treatment associated with a longer patient delay. A lump on the neck or facial swelling associated with a shorter PHC delay. Conversely, if symptoms were treated as an infection, PHC delay was longer. The treatment modality and tumor site affected SC delay. CONCLUSIONS: Patient delay stands as the most notable factor contributing to delays before treatment. HNC symptom awareness thus remains especially important among HNC risk groups.

Twist and snai1 expression in pharyngeal squamous cell carcinoma stroma is related to cancer progression.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis since tumor cells attain fibroblast-like features enabling them to invade to surrounding tissue. Two transcription factors, TWIST and SNAI1, are fundamental in regulating EMT. METHODS: Immunohistochemistry was used to study the expression of TWIST and SNAI1 in 109 pharyngeal squamous cell carcinomas. RESULTS: Tumors with intense stromal staining of TWIST relapsed more frequently (p = 0.04). Tumors with both positive TWIST and SNAI1 immunoreactivity in the stroma were at least Stage II (p = 0.05) and located more often in hypopharynx (p = 0.035). Tumors with negative immunostaining of TWIST and SNAI1 in the stromal compartment were smaller (T1-2) (p = 0.008), less advanced (SI-II) (p = 0.031) and located more often in the oropharynx (p = 0.007). Patients with negative SNAI1 and TWIST immunostaining in tumor stroma had a better 5-year disease-specific and overall survival (p = 0.037 and p = 0.014 respectively). CONCLUSION: TWIST and SNAI1 expression in stromal cells is associated with clinical and histopathological characteristics that indicate progressive disease. Negative expression of these EMT-promoting transcription factors predicts a better outcome.

SIP1 predicts progression and poor prognosis in pharyngeal squamous cell carcinoma.

OBJECTIVES: The epithelial-mesenchymal transition (EMT) is a crucial process in tumorigenesis that enables tumor cells to invade and metastasize. The transcription factors SIP1, SLUG, ZEB1, SNAI1, and TWIST are fundamental in regulating EMT. We investigated the relationships between several clinicopathological variables, prognosis, and SIP1, SLUG, or ZEB1 in a retrospective pharyngeal squamous cell carcinoma (PSCC) cohort. STUDY DESIGN: Immunohistochemistry was used to evaluate the expression of SIP1, SLUG, and ZEB1 in 108 tumor samples from a retrospective cohort of patients with PSCC. RESULTS: Tumors with positive epithelial SIP1 immunostaining were more advanced (SIII-IV, p=0.02) and had more lymph node metastases (p=0.04) than SIP1-negative tumors. Tumors with positive stromal staining of SIP1 relapsed more often than SIP1-negative tumors (p=0.007). Negative SIP1 immunoreactivity correlated significantly with better disease-specific survival (DSS) and better overall survival (OS) (p=0.012 and p=0.003 for epithelial reactivity, p=0.018 and p=0.003 for stromal reactivity, respectively). Lack of epithelial SIP1 expression remained an independent and favorable prognostic factor in a Cox proportional hazards model (p=0.046), together with high Karnofsky performance status score and low T class (p<0.001 for both). Co-expression of SNAI1, TWIST, and SIP1 in tumor epithelium predicted even shorter DSS than SIP1 expression alone (p<0.001) in the present study cohort. CONCLUSIONS: SIP1 is related to cancer progression and appears to be an independent prognostic factor in PSCC.

Transcription factor snail1 expression and poor survival in pharyngeal squamous cell carcinoma.

Snail1, a key regulator of epithelial-mesenchymal transition (EMT), plays an important role in tumour progression. Previous studies of snail1 have mainly focused on the epithelial tumour cells. The objective of this study was to evaluate the expression of snail1 protein in endothelial cells, stromal myofibroblasts and malignant epithelial cells of pharyngeal squamous cell carcinomas (PSCC), as well as its relation to clinicopathological features and survival. One hundred and ten tissue microarray samples were analyzed for snail1 expression using immunohistochemistry. In endothelial cells snail1 expression was observed in 51 (48%) of 107 cases and it predicted reduced disease specific survival (DSS) (p=0.009). In 49 (46%) tumour samples snail1 immunostaining was detected in stromal myofibroblasts and there was a tendency to poorer DSS in that group (p=0.067). Snail1 expression in endothelial cells and stromal myofibroblasts is also associated with hypopharyngeal tumours (p=0.01 and p=0.038 respectively), increasing T category (T3-4) (p=0.005, p=0.037 respectively) and poorer general condition of the patient (Karnofsky performance status score <70; p=0.029, p=0.039 respectively). Moreover endothelial expression correlated with advanced stage (III-IV) (p=0.005) and poorer differentiation (grade 2-3; p=0.012). In malignant epithelial cells snail1 immunostaining was detected in 75 of 110 cases (68%). Expression of the protein was more common in hypopharyngeal tumours (p=0.044). Snail1 positive tumours associated with a lower Karnofsky performance status score (p=0.039) and regional failure (p=0.042). Our findings indicate that snail1 protein expression in endothelial cells and to some extent also in tumour stromal myofibroblasts seems to be a predictor of poor survival in PSCC. The presence of snail1 protein in tumour microenvironment rather than in malignant epithelial tumour cells may induce tissue remodelling and tumour progression.