A qualitative study of the experience of oral cancer among Taiwanese men

The incidence and mortality of oral cancer in Taiwanese men have increased over the past decade, primarily associated with a surge in the popularity of betel quid chewing. The aim of this study was to examine the experience of six Taiwanese men with oral cancer, who were aged between 40 and 60 years, using a qualitative approach. The three major themes emerging from the data include: (i) understanding the cancer diagnosis; (ii) the challenges of cancer treatment; and (iii) adapting to difference. Increasing nurses' understanding of the experiential aspects of oral cancer in this population is required if nurses are to develop successful health promotion programmes and nursing interventions to meet these patients' needs.

Epidemiology and risk factors of oral cancer in South Africa

Head and neck cancers are some of the leading cancers in the coloured and black South African male population and the perception exists that the incidence rates are rising. Aims: To determine the standardised morbidity rates and some of the risk factors for oral cancer in South Africa. Methods: Using histologically verified data from the National Cancer Registry, the age standardised incidence rates (ASIR) and life-time risks (LR) of oral cancer in South Africa were calculated for 1988-1991.2. In an ongoing case control study (1995 +) among black patients in Johannesburg/Soweto, adjusted odds ratios for developing oral cancers in relation to tobacco and alcohol consumption were calculated. Results: Coloured males vs. females: ASIR 13.13 vs. 3.5 (/100,000/year), LR 1:65 vs. 1:244. Black males vs. females: ASIR 9.06 vs. 1.75, LR 1:86 and 1:455. White males vs. females: ASIR 8.06 vs. 3.18, LR 1:104 vs. 1:278. Asian males vs. females: ASIR 5.24 vs. 6.66, LR 1:161 vs. 1:125. The odds ratio for oral cancer in black males in relation to smoking was 7.0 (95% CI 3.0-14.6) and daily alcohol consumption 1.3 (95% CI 0.6-2.8). In black females the odds ratios in relation to smoking were 3.9 (95% CI 1.7 8.9) and daily alcohol consumption 1.7(95% CI 0.7-4.1). Conclusions: The risk factors for oral cancer in South Africa are multiple and gender discrepancies in ASIR and LR signal differences in exposure to carcinogens. It is unclear whether the incidence of oral cancers will rise in the future.

Comparison of oropharyngeal and oral cavity squamous cell cancer incidence and trends in New Zealand and Queensland, Australia

Background Increases in the incidence of squamous cell oropharyngeal cancer (OPC) have been reported from some countries, but have not been assessed in Australia or New Zealand. This study examines trends for squamous cell OPC and squamous cell oral cavity cancer (OCC) in two similarly sized populations, New Zealand and Queensland, Australia. Methods Incidence data for 1982–2010 were obtained from the respective population-based cancer registries for squamous cell OPC and OCC, by subsite, sex, and age. Time trends and annual percentage changes (APCs) were assessed by joinpoint regression. Results The incidence rates of squamous cell OPC in males in New Zealand since 2005 and Queensland since 2006 have increased rapidly, with APCs of 11.9% and 10.6% respectively. The trends were greatest at ages 50–69 and followed more gradual increases previously. In females, rates increased by 2.1% per year in New Zealand from 1982, but by only 0.9% (not significant) in Queensland. In contrast, incidence rates for OCC decreased by 1.2% per year in males in Queensland since 1982, but remained stable for females in Queensland and for both sexes in New Zealand. Overall, incidence rates for both OCC and OPC were substantially higher in Queensland than in New Zealand. In males in both areas, OPC incidence is now higher than that of OCC. Conclusions Incidence rates of squamous cell OPC have increased rapidly in men, while rates of OCC have been stable or reducing, showing distinct etiologies. This has both clinical and public health importance, including implications for the extension of human papilloma virus (HPV) vaccination to males.

Organotypic culture of normal, dysplastic and squamous cell carcinoma-derived oral cell lines reveals loss of spatial regulation of CD44 and p75(NTR) in malignancy

Oral squamous cell carcinomas (OSCC) often arise from dysplastic lesions. The role of cancer stem cells in tumour initiation is widely accepted, yet the potential existence of pre-cancerous stem cells in dysplastic tissue has received little attention. Cell lines from oral diseases ranging in severity from dysplasia to malignancy provide opportunity to investigate the involvement of stem cells in malignant progression from dysplasia. Stem cells are functionally defined by their ability to generate hierarchical tissue structures in consortium with spatial regulation. Organotypic cultures readily display tissue hierarchy in vitro; hence, in this study, we compared hierarchical expression of stem cell-associated markers in dermis-based organotypic cultures of oral epithelial cells from normal tissue (OKF6-TERT2), mild dysplasia (DOK), severe dysplasia (POE-9n) and OSCC (PE/CA P J15). Expression of CD44, p75NTR, CD24 and ALDH was studied in monolayers by flow cytometry and in organotypic cultures by immunohistochemistry. Spatial regulation of CD44 and p75NTR was evident for organotypic cultures of normal (OKF6-TERT2) and dysplasia (DOK and POE-9n) but was lacking for OSCC (PE/CA PJ15)-derived cells. Spatial regulation of CD24 was not evident. All monolayer cultures exhibited CD44, p75NTR, CD24 antigens and ALDH activity (ALDEFLUOR® assay), with a trend towards loss of population heterogeneity that mirrored disease severity. In monolayer, increased FOXA1 and decreased FOXA2 expression correlated with disease severity, but OCT3/4, Sox2 and NANOG did not. We conclude that dermis-based organotypic cultures give opportunity to investigate the mechanisms that underlie loss of spatial regulation of stem cell markers seen with OSCC-derived cells.

Tumor-suppressor gene promoter hypermethylation in saliva of head and neck cancer patients

Head and neck squamous cell carcinoma (HNSCC) accounts for a bulk of the oral and laryngeal cancers, the majority (70%) of which are associated with smoking and excessive drinking, major known risk factors for the development of HNSCC. In contrast to reports that suggest an inverse relationship between smoking and global DNA CpG methylation, hypermethylation of promoters of a number of genes was detected in saliva collected from patients with HNSCC. Using a sensitive methylation-specific polymerase chain reaction (MSP) assay to determine specific methylation events in the promoters of RASSF1A, DAPK1, and p16 genes, we demonstrate that we can detect tumor presence with an overall accuracy of 81% in the DNA isolated from saliva of patients with HNSCC (n = 143) when compared with the DNA isolated from the saliva of healthy nonsmoker controls (n = 31). The specificity for this MSP panel was 87% and the sensitivity was 80%(with a Fisher exact test P < .0001). In addition, the test panel performed extremely well in the detection of the early stages of HNSCCs, with a sensitivity of 94% and a specificity of 87%, and a high. concordance value of 0.8, indicating an excellent overall agreement between the presence of HNSCC and a positive MSP panel result. In conclusion, we demonstrate that the promoter methylation of RASSF1A, DAPK1, and p16 MSP panel is useful in detecting hypermethylation events in a noninvasive manner in patients with HNSCC.

miRNAs in head and neck cancer revisited

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer. Tobacco smoking, alcohol consumption and human papilloma virus (HPV) infections have been associated with the occurrence of HNSCC. Despite advances that have been made in HNSCC treatment, smoking-associated HNSCC patients still exhibit a poor 5 year survival rate (30-50 %) and a concomitant poor quality of life. The major clinical challenge to date lies in the early detection of dysplastic lesions,which can progress to malignancy. In addition, there are currently no tools available to monitor HNSCC patients for early stages of local recurrences or distant metastases. In the recent past, micro-RNAs (miRNA) have been assessed for their role in cancer initiation and progression, including HNSCC. It is now well-established that deregulation of these single stranded, small non-coding, 19-25 nt RNAs can e.g. enhance the expression of oncogenes or subdue the expression of tumor suppressor genes. The aims of this review are three-fold: first to retrieve from the literature miRNAs that have specifically been associated with HNSCC, second to group these miRNAs into those regulating tumor initiation, progression and metastasis, and third to discern miRNAs related to smoking-associated HNSCC versus HPV-associated HNSCC development. This review gives an overview on the miRNAs regulating the development of head and neck cancers. The ultimate establishment of miRNA expression profiles that are HNSCC specific, and miRNAs that orchestrate altered gene and protein expression levels in HNSCC, could pave the way for a better understanding of the mechanism underlying its pathogenesis and the development of novel, targeted therapies.

CDKN2A mutation in a non-FAMMM kindred with cancers at multiple sites results in a functionally abnormal protein

The CDKN2A gene encodes p16 (CDKN2A), a cell-cycle inhibitor protein which prevents inappropriate cell cycling and, hence, proliferation. Germ-line mutations in CDKN2A predispose to the familial atypical multiple-mole melanoma (FAMMM) syndrome but also have been seen in rare families in which only 1 or 2 individuals are affected by cutaneous malignant melanoma (CMM). We therefore sequenced exons 1alpha and 2 of CDKN2A using lymphocyte DNA isolated from index cases from 67 families with cancers at multiple sites, where the patterns of cancer did not resemble those attributable to known genes such as hMLH1, hMLH2, BRCA1, BRCA2, TP53 or other cancer susceptibility genes. We found one mutation, a mis-sense mutation resulting in a methionine to isoleucine change at codon 53 (M531) of exon 2. The individual tested had developed 2 CMMs but had no dysplastic nevi and lacked a family history of dysplastic nevi or CMM. Other family members had been diagnosed with oral cancer (2 persons), bladder cancer (1 person) and possibly gall-bladder cancer. While this mutation has been reported in Australian and North American melanoma kindreds, we did not observe it in 618 chromosomes from Scottish and Canadian controls. Functional studies revealed that the CDKN2A variant carrying the M531 change was unable to bind effectively to CDK4, showing that this mutation is of pathological significance. Our results have confirmed that CDKN2A mutations are not limited to FAMMM kindreds but also demonstrate that multi-site cancer families without melanoma are very unlikely to contain CDKN2A mutations.

Self-management of cancer treatment-related fatigue, nausea, vomiting and oral mucositis in Chinese cancer patients

Background: Treatment-related symptoms continue to place a significant burden on many cancer patients. Many side effects require patients to engage in a range of self-management actions. While some studies have explored self-management of treatment-related side effects in Western settings, very few studies were identified that described the self-management practices of cancer patients in China. Objective: The purposes of this study are to: (1) Investigate Chinese cancer patients. self-management behaviours in dealing with the fatigue, nausea/vomiting and oral mucositis that result from treatment, as well as the perceived effectiveness of these behaviours and related self-efficacy in performing them. (2) Explore factors influencing symptom self-management behaviours using the Cancer Symptom Self-management Framework based on Grey, Knafl and McCorkle.s (2006) self-management framework as a guide. Methods: This study was divided into two phases. Phase One consisted of the translation and modification of two instruments. The adaptation of these instruments to ensure applicability in the Chinese context was achieved through semi-structured interviews with six cancer patients, and content evaluation with eight experienced oncology nurses. A pilot study was conducted with nine cancer patients to trial the questionnaire set in the Chinese context. Based on the results of Phase One, Phase Two involved a cross-sectional survey of Chinese cancer patients undergoing cancer treatment using these instruments. A total of 277 chemotherapy patients with fatigue and/or nausea and vomiting, and 100 radiotherapy patients with oral mucositis were surveyed. Results: Participants in this study reported a variety of self-management behaviours to cope with fatigue, nausea, vomiting and oral mucositis. There are some consistencies as well disparities between strategies that are frequently used and those rated as effective. For fatigue self-management, participants were more likely to use strategies related to rest and sleep, while activity enhancement strategies were rated as achieving higher relief. For nausea and vomiting self-management, dietary modification and taking medication were most frequently used and rated as moderately effective. Psychological strategies were used by more than a third of participants and were rated as mildly effective. Some other infrequently used strategies, such as distraction by keeping busy and acupressure, were rated as moderately effective. For oral mucositis self-management, having soft, bland food and keeping the mouth moisturised were most frequently reported and they were rated as achieving moderate relief. A prescribed mouthwash was used by most but not all participants and brought moderate relief. In general, patients had low-to-moderate self-efficacy in nausea and vomiting self-management behaviours, moderate self-efficacy in fatigue self-management behaviours, and low-to-moderate self-efficacy in oral mucositis self-management behaviours. In terms of the factors influencing symptom self-management, different predictors were identified affecting engagement in fatigue, nausea/vomiting and oral mucositis self-management behaviours. Self-efficacy scores of different behaviours were consistently found to be a positive predictor of the relief level from corresponding behaviours, after controlling for other variables. Perceived social support from health care professionals was identified as an important factor influencing nausea and vomiting self-management behaviours, while neighbourhood support was important for fatigue self-management. In addition, symptom distress was identified as an important factor influencing nausea and vomiting self-management. Conclusion: Similar to reports from overseas, Chinese cancer patients initiate a wide range of self-management behaviours in response to treatment-related side effects. While some behaviours were reported to provide relief, many did not. Given these results, this study has a number of practical implications for health care professionals, particularly in relation to developing tailored self-management programs for fatigue, nausea, vomiting and oral mucositis. Additionally, this study suggests a number of theoretical implications and directions for future research. It is envisaged that these recommendations may pave the way for further studies understanding and promoting cancer symptom self-management in Chinese people affected by cancer.

Alternative analytical methods for the identification of cancer-related symptom clusters

Advances in symptom management strategies through a better understanding of cancer symptom clusters depend on the identification of symptom clusters that are valid and reliable. The purpose of this exploratory research was to investigate alternative analytical approaches to identify symptom clusters for patients with cancer, using readily accessible statistical methods, and to justify which methods of identification may be appropriate for this context. Three studies were undertaken: (1) a systematic review of the literature, to identify analytical methods commonly used for symptom cluster identification for cancer patients; (2) a secondary data analysis to identify symptom clusters and compare alternative methods, as a guide to best practice approaches in cross-sectional studies; and (3) a secondary data analysis to investigate the stability of symptom clusters over time. The systematic literature review identified, in 10 years prior to March 2007, 13 cross-sectional studies implementing multivariate methods to identify cancer related symptom clusters. The methods commonly used to group symptoms were exploratory factor analysis, hierarchical cluster analysis and principal components analysis. Common factor analysis methods were recommended as the best practice cross-sectional methods for cancer symptom cluster identification. A comparison of alternative common factor analysis methods was conducted, in a secondary analysis of a sample of 219 ambulatory cancer patients with mixed diagnoses, assessed within one month of commencing chemotherapy treatment. Principal axis factoring, unweighted least squares and image factor analysis identified five consistent symptom clusters, based on patient self-reported distress ratings of 42 physical symptoms. Extraction of an additional cluster was necessary when using alpha factor analysis to determine clinically relevant symptom clusters. The recommended approaches for symptom cluster identification using nonmultivariate normal data were: principal axis factoring or unweighted least squares for factor extraction, followed by oblique rotation; and use of the scree plot and Minimum Average Partial procedure to determine the number of factors. In contrast to other studies which typically interpret pattern coefficients alone, in these studies symptom clusters were determined on the basis of structure coefficients. This approach was adopted for the stability of the results as structure coefficients are correlations between factors and symptoms unaffected by the correlations between factors. Symptoms could be associated with multiple clusters as a foundation for investigating potential interventions. The stability of these five symptom clusters was investigated in separate common factor analyses, 6 and 12 months after chemotherapy commenced. Five qualitatively consistent symptom clusters were identified over time (Musculoskeletal-discomforts/lethargy, Oral-discomforts, Gastrointestinaldiscomforts, Vasomotor-symptoms, Gastrointestinal-toxicities), but at 12 months two additional clusters were determined (Lethargy and Gastrointestinal/digestive symptoms). Future studies should include physical, psychological, and cognitive symptoms. Further investigation of the identified symptom clusters is required for validation, to examine causality, and potentially to suggest interventions for symptom management. Future studies should use longitudinal analyses to investigate change in symptom clusters, the influence of patient related factors, and the impact on outcomes (e.g., daily functioning) over time.

Risk of second cancer after lymphohematopoietic neoplasm

People living with lymphohematopoietic neoplasms (LHNs) are known to have increased risks of second cancer; however, the incidence of second cancers after LHNs has not been studied extensively in Australia. The Australian Cancer Database was used to analyze site-specific risk of second primary cancer after LHNs in 127,707 patients diagnosed between 1983 and 2005. Standardized incidence ratios (SIRs) were calculated using population rates. Overall, patients with an LHN had nearly twice the risk of developing a second cancer compared to the Australian population. Among 40,321 patients with non-Hodgkin's lymphoma (NHL), there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, connective tissue and peripheral nerves, eye, thyroid, Hodgkin's disease (HD) and myeloid leukemia. Among 6,396 patients with HD, there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, oral cavity and pharynx, female breast, uterine cervix, testis, thyroid, NHL and myeloid leukemia. Among the 33,025 patients with lymphoid and myeloid leukemia, significant excess were seen for cancers of the lip, eye, connective tissue and peripheral nerves, NHL and HD. Among the 13,856 patients with plasma cell tumors, there was over fourfold significant increase for melanoma, cancer of the connective tissue and peripheral nerves and myeloid leukemia. Our findings provide evidence of an increased risk of cancer, particularly ultraviolet radiation- and immunosuppression-related cancers, after an LHN in Australia. Copyright © 2010 UICC.

Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.