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1
Oguejiofor, Kenneth Kenechukwu. "Prognostic markers in oropharyngeal cancers." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/prognostic-markers-in-oropharyngeal-cancers(fda96224-657d-4049-ae6c-50db33a5388a).html.
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Introduction: Human papillomavirus (HPV) is changing the prevalence, survival and treatment paradigms in oropharyngeal squamous cell carcinoma (OPSCC). Improved survival of patients with HPV positive compared to HPV negative OPSCC has led to trials of treatment de-escalation. Current HPV detection methods are imprecise, therefore standardised assessment of transcriptionally active HPV in OPSCC is required. Furthermore, the differences in immune characteristics and/or the hypoxia response/effects could explain observed differences in prognosis between HPV positive and negative OPSCC. Rigorous HPV detection and subsequent biomarker evaluation should provide additional information required before introduction of treatment de-escalation in broad patient groupings. Methods: The study cohort was 218 patients with OPSCC who received radiotherapy with curative intent. HPV status was determined on pre-treatment, formalin-fixed paraffin-embedded blocks using: 1) polymerase chain reaction (PCR); 2) in-situ hybridisation (ISH) and 3) immuno-histochemistry (IHC). QuantiGene multiplex assay was designed to detect mRNA of reference sequences of the common high-risk HPV types (16, 18, 33, 35, 45, 52 and 58). HPV detection methods were compared with mRNA quantification. Multimarker IHC of immune cell markers using chromogenic and fluorescent staining was performed, analysed and compared with single marker IHC using automated multispectral image analysis. A validated multiplex IHC method was used for a) chromogenic (CD3, CD4, CD8, and FoxP3) and b) fluorescent (CD8, CD68 and PD1/PD-L1) evaluation in tumour and stroma compartments. Single marker IHC was used to investigate tumour hypoxia markers (HIF-1α and CA-IX) in HPV positive and negative OPSCC. Results: p16 IHC and ISH were the most sensitive and specific, respectively, for classifying HPV status. The combination of the three tests had the highest positive/negative predictive values compared with QuantiGene mRNA detection. Multiplex validation showed that, for serial sections up to 6 μm apart, there were highly significant correlations (P<0.0001) between single and multiplex counts for both chromogenic and fluorescent IHC. Overall there was less variation in cell counts with fluorescent staining when compared to chromogenic staining. Multiplex IHC of TILs in HPV positive and negative OPSCC showed higher infiltration in both tumour and stromal areas of CD3+CD4+ and CD3+CD8+ T cells but not CD4+FoxP3 Tregs in HPV positive compared with HPV negative OPSCC. Only CD3+CD8+ stromal and not tumour area infiltration was associated with increased survival (P=0.02). PD-L1 expression was higher in HPV negative OPSCC and this was related to macrophage (CD68) expression of PD-L1. In HPV negative tumours infiltration with CD68+PD-L1 was associated with a good prognosis. HPV negative patients had higher expression of HIF-1α but not CA-IX. High expression of both markers was associated with a poor prognosis irrespective of HPV status. Conclusions: There are other prognostic factors operating in the larger subdivision of HPV positive and negative OPSCC. Precise HPV detection and inclusion of other prognostic factors is required before treatment de-escalation is used. Expression of immune inhibitory factors (PD1/PD-L1) alone without contextualisation with immune cell density is insufficient for patient prognostication and potential selection for therapy using immune checkpoint inhibitors. Hypoxia modification of radiotherapy should be explored in both HPV positive and negative OPSCC.
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Siembida, Jakub. "Implications of transoral robotic surgery on the field of otolaryngology: contemporary management of oropharyngeal cancers." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12627.
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Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.The incidence and prevalence of cancers of the oropharynx has been on the rise over recent years, with approximately 13,000 new cases diagnosed each year in the United States. Increased incidence has been linked to increased alcohol consumption, tobacco use, and the human papilloma virus, and stresses the importance for the development of modern treatments. The majority of oral cancers are squamous cell carcinomas, originating in the mucosal tissue layer and metastasizing throughout the neck to surrounding lymph nodes and organs. Due to the difficulty in the detection of oropharyngeal cancers, they are often detected in late stage and must be removed surgically to maximize survival. Treatment of head and neck cancers falls under the responsibility of otolaryngologists, who utilize a wide variety of surgical and non-surgical procedures to minimize morbidity and maximize the patient's chances of survival while maintaining high quality of life. The classic approach to the treatment of head and neck cancers has been a combination of neck dissection, removal of lymph nodes, and radiation therapy to obliterate the disease in its entirety. Saving the life of the patient often results in many complications as a result of the invasive and aggressive treatments. In order to maximize the removal of the cancer, collateral damage to surrounding nerves, muscles, and other essential tissues often occurs with dissection of the neck. This radical approach often leaves little regard for the future quality of life of the patient, and alternatives are being sought to address these needs. Along with other surgical fields, otolaryngology is moving toward a minimally invasive approach in the treatment of oropharyngeal cancers. With the advent of modern technology and miniaturization of instruments, minimally invasive procedures such as endoscopic surgery, laser surgery, and concentrated radio- and chemotherapeutics have allowed otolaryngologists a greater range of possible treatments for their patients. In the recent evolution of surgical treatment, robots have been developed and adapted to assist surgeons in performing difficult procedures which are otherwise not possible. Utilizing robotic arms under the control of a trained surgeon, transoral robotic surgery allows for the removal of diseased tissue via the oral cavity. This recent procedural development allows surgeons to remove cancerous lesions from the head and neck without the need for a large external incisions. This approach minimizes tissue trauma, leaving unrelated organs and tissues of the neck intact. By reducing damage to surrounding structures, transoral robotic surgery improves the prognosis of, and speeds post-surgical recovery of the patient. Transoral robotic surgery is quickly gaining traction as an acceptable alternative to open surgeries in the management of head and neck cancers, allowing for preservation of structure and function. Although promising, many variables must be considered to determine whether it is in fact the most appropriate treatment. Factors such as quality of life, the ability to swallow and speak, recovery time, comorbidity, and survival must all be taken into consideration. While transoral robotic surgery presents many benefits to the surgical team and patient, there are inevitably some drawbacks and limitations to this new and promising technology. Only recently developed and approved for the minimally invasive treatment of head and neck cancers, it presents novel and exciting possibilities to the field of otolaryngology. By analyzing the literature on surgical treatment of oropharyngeal cancers over the past twenty years, I weigh the costs and benefits of transoral robotic surgery against traditional approaches to determine what role this new procedure plays in the contemporary management of oropharyngeal cancer.
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Auluck, Ajit. "Epidemiological shifts and risk behaviours for oral and oropharyngeal cancers in multicultural population of British Columbia, Canada." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/41390.
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Although smoking prevalence in British Columbia (BC) is decreasing, numbers of oral cancers are increasing. This change may reflect new emerging risk factors, including an increase in human papillomavirus (HPV) infections and greater immigration from high-risk countries. Currently, in BC there is no data on the trends in oral cancer incidence and survival by ethnicity or by etiologically clustered oral cancer subsites (oral cavity cancers, OCC, which are predominantly tobacco related; and oropharyngeal cancers, OPC, which are predominantly HPV-related).
Oral cancers were retrieved from BC Cancer Registry (BCCR) from 1980 to 2006 and the following information collected: names, demographic, tumor, treatment and outcome information. When specific information was not complete, chart review was done. South Asian (SA) or Chinese ethnicities were determined by using previously generated ethnic surname list. Age-adjusted incidence rates (AAIR), age-specific incidence rates (ASIR) and 5-year survival rates for these three populations were calculated by sex, grouping the cancers into etiologically clustered subsites. Calculations were done for each year from 1980 to 2006. An ethnographic study was then conducted to describe the patterns of access, use and perceptions of SA men towards chewing tobacco-containing betel quid (BQ). Extensive field work included participant observations and semi-structured interviews.
We have for the first time shown that the incidence of HPV-related OPC has surpassed that of tobacco-related OCC in men. For female, the incidence rates of OPC increased and OCC unchanged. AAIR for OCC was highest in SA males and females while rates of OPC were highest in general population males and Chinese males. Survival rates for OCC were unchanged and for OPC improved in males. SA had poorest survival rates for OCC. Ethnographic findings revealed that among SA males chewing tobacco-containing BQ was viewed as a culturally accepted practice. Availability of BQ, perceived benefits of chewing, ability to conceal the habit, and a lack of awareness of health risks also supported chewing practices.
These findings provide a strong foundation for continued work in this field aimed at identifying effective prevention and treatment strategies for oral cancer.Dentistry, Faculty of
Graduate
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Auluck, Ajit. "Epidemiological shifts and risk behaviors for oral and oropharyngeal cancers in multicultural population of British Columbia, Canada." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/41390.
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Although smoking prevalence in British Columbia (BC) is decreasing, numbers of oral cancers are increasing. This change may reflect new emerging risk factors, including an increase in human papillomavirus (HPV) infections and greater immigration from high-risk countries. Currently, in BC there is no data on the trends in oral cancer incidence and survival by ethnicity or by etiologically clustered oral cancer subsites (oral cavity cancers, OCC, which are predominantly tobacco related; and oropharyngeal cancers, OPC, which are predominantly HPV-related).
Oral cancers were retrieved from BC Cancer Registry (BCCR) from 1980 to 2006 and the following information collected: names, demographic, tumor, treatment and outcome information. When specific information was not complete, chart review was done. South Asian (SA) or Chinese ethnicities were determined by using previously generated ethnic surname list. Age-adjusted incidence rates (AAIR), age-specific incidence rates (ASIR) and 5-year survival rates for these three populations were calculated by sex, grouping the cancers into etiologically clustered subsites. Calculations were done for each year from 1980 to 2006. An ethnographic study was then conducted to describe the patterns of access, use and perceptions of SA men towards chewing tobacco-containing betel quid (BQ). Extensive field work included participant observations and semi-structured interviews.
We have for the first time shown that the incidence of HPV-related OPC has surpassed that of tobacco-related OCC in men. For female, the incidence rates of OPC increased and OCC unchanged. AAIR for OCC was highest in SA males and females while rates of OPC were highest in general population males and Chinese males. Survival rates for OCC were unchanged and for OPC improved in males. SA had poorest survival rates for OCC. Ethnographic findings revealed that among SA males chewing tobacco-containing BQ was viewed as a culturally accepted practice. Availability of BQ, perceived benefits of chewing, ability to conceal the habit, and a lack of awareness of health risks also supported chewing practices.
These findings provide a strong foundation for continued work in this field aimed at identifying effective prevention and treatment strategies for oral cancer.
5
Chiriseri, Edina. "Human papilloma virus and oral cancers : sexual behaviour as a risk factor." Thesis, De Montfort University, 2017. http://hdl.handle.net/2086/16084.
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AIM & OBJECTIVES: Human papilloma virus (HPV) has been related to cervical infection, however, its part in Head and Neck Squamous Cell Carcinoma (HNSCC) is still debatable and is easy to refute. Suspicion of HPV causation is heightened when carcinomas arise in patients that are young and have never smoked. The present UK based study undertaken at Northampton NHS Trust endeavoured to determine the extent to which HPV is an entity in HNSCC in the UK. Furthermore, the study investigated whether sexual behaviour (as measured by sexual health clinic (SHC) attendance) is linked the acquisition of HPV associated HNSCC in young age groups. HNSCC incidences and sexual trends in the UK were collected from publicly available databases to identify if there were any changes at a national level in sexual behaviours and their influence on HNSCC in young age groups. MATERIALS & METHODS: PCR was used to evaluate the presence of HPV in biopsy samples from of 99 patients diagnosed with HNSCC at Northampton Hospital from 2006 to 2014. Patient demographics on age, sex, smoking, alcohol use and SHC attendance were also collected. All HPV PCR positive biopsies were further genotyped using an ABI 3130xl genetic analyser. Databases in the UK; including GLOBOCAN, NATSAL and PHE were searched for data on HNSCC prevalence, sexual behaviour trends and vaccine uptake. Multinomial regression explored the relationship between HPV positivity and sex, age, smoking, drinking, race and SHC attendance. RESULTS: PCR showed that 25.2% (25/99) of biopsies tested were positive for HPV and were all obtained from white participants. Most specimens (23, 92%) were high-risk (HR) HPV 16 positive with a mean age of 56 for HPV positivity and 72% of the cases 50-60 years old. Smokers were 11% in total (11/99) with most 88.9% participants (88/99) being non-smokers. HPV positivity was strongly linked with non-smoking history (p < 0.001); no alcohol abuse (p < 0.001); male gender (p < 0.001); young age less than 60 years (p < 0.001) and SHC attendance (p < 0.001). A Kruskal-Wallis post hoc test affirmed the impact of age on HPV positivity (p= < 0.05). GLOBOCAN and Cancer Research demonstrated a rising UK HNSCC pattern of over 200% for both sexes from 1975 to 2011. The three NATSAL surveys undertaken in 1990-1991, 1999-2001 and 2010-2012 demonstrated an overall increase in opposite and same sex partners. The UK average of individuals engaging in oral sex was in the younger age groups of between 16 and 54 with at least 70% of males and 63% females of that age engaging in oral sex. Finally, NASTAL 1, 2 and 3 surveys reported 20 vs 15; 25 vs 55; 55 vs 65 of males and females respectively with more than 10 sexual partners to have attended the SHC. The UK immunization take-up was over 90% countrywide. CONCLUSION: Few research studies have been conducted to date on HPV as a cause of HNSCC in the UK. The present research showed 25.2% of HNSCC to be caused by HPV, with the high risk (HR) genotype 16 (the leading cause of cervical cancer) accounting for 92% (23/25) of the cases. These outcomes affirmed the high prevalence of HR-HPV in HNSCC, with a rate of 25.2% similar to those reported previously. Routine HPV testing in those aged below 60 is therefore warranted. Smoking and drinking showed negative correlation; the young age of below 60 and attendance of the SHC for both sexes showed a positive correlation with HPV positive HNSCC. NATSAL data showed increased sexually risky behaviour coupled with attending the SHC in younger ages for both sexes. Increased sexually risky behaviour as shown in NASTAL surveys may be the reason why young age and SHC attendance is positively correlated with HPV HNSCC. The study highlights a conceivable relationship between HPV positive HNSCC in those under 60 years with no smoking history who attended the SHC. Smoking and drinking are known risks for HNSCC in those past 65 years of age; the negative association with HPV HNSCC in the young in the present research revealed smoking and drinking to have reduced association with HPV HNSCC. The reported HR-HPV positive HNSCC in young age groups inform future vaccination strategies and consequently decrease the quantity of HPV HNSCC's.
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Pirotte, Evelyne. "PARP inhibition in novel oropharyngeal cancer cell lines." Thesis, Cardiff University, 2017. http://orca.cf.ac.uk/109437/.
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In recent decades many developed countries have seen unprecedented increases in incidence of Human Papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC). HPV-positive OPSCC represents a new disease entity and preclinical assessment of novel therapies is hampered by a lack of relevant in vitro models. It is well-established that HPV-positive OPSCC patients generally survive longer than HPV-negative patients, and this may be partly attributable to defective repair of DNA double-strand-breaks in HPV-positive tumours. This study aimed to develop novel cell line models of HPV-OPSCC and use them, and previously validated lines, to test the hypothesis that defective DNA repair in HPV-positive cells could be exploited by synthetic lethal therapy using the Poly (ADP-ribose) polymerase (PARP) inhibitor Olaparib. Two novel HPV-positive OPSCC cell lines were derived and characterised. mRNA sequencing confirmed expression of the HPV oncogenes and HPV integration state, but did not show consistent differences in transcript levels of genes involved in DNA repair between HPV-positive and negative lines. The effects of Olaparib were assessed in a panel of eight cell lines, including effects on colony formation, cell cycle distribution, DNA double-strand-break persistence and p53 activity. All lines were sensitive to high doses of Olaparib (10 μM), however at doses between 0.5-1 μM, the surviving fractions differed significantly between lines. Two HPV-positive lines were sensitive to Olaparib (Surviving Fraction (SF) < 40%), and two were resistant (SF > 80%). Neither HPV-status, nor basal levels of PARP correlated with Olaparib sensitivity. The data were not consistent with the original hypothesis, but did suggest that monotherapy with PARP inhibitors might be useful in some OPSCC patients. The study also included an investigation into the natural history of HPV in the oropharynx. This demonstrated that HPV infection is a rare event in non-malignant tonsil tissue (prevalence of 0%: 95% confidence interval (CI) 0-0.58%).
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Lind, Mimmi. "Recurrence detection in oropharyngeal cancer –a retrospective cohortstudy." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-93177.
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Introduction: Oropharyngeal cancer (OPC) is a highly prevalent malignancy worldwideaffecting the tonsils, the soft palette and the base of the tongue. OPC has a high risk ofrecurrence. Patients are offered a 5-year follow-up program in order to discover earlyrecurrences. However, there exists some controversy regarding the benefit of this follow-up indetecting early recurrences. Objective: The primary aim of this study was to investigate whether recurrences of OPC weredetected in patient-initiated appointments or during routine follow-up. The secondary aim wasto compare the survival between these groups. Method and materials: This study is a retrospective cohort study regarding recurrencedetection among patients diagnosed with OPC. The Örebro Head- and neck cancer registerwas used to identify patients with recurrence of OPC. Additional data was collected frommedical records. Results: A total of 75 patients were included. Routine follow-up detected 50.7% ofrecurrences while patient-initiated visits detected 42.7% of recurrences. No statisticallysignificant difference was found in survival between these groups Conclusion: In contradiction to our hypothesis most of the recurrences were detected atroutine follow-up. There was no statistically significant difference in survival between thetwo ways of detection. These results indicate that our current follow-up program has animportance in detecting early recurrences and should not be altered.
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Ward, Matthew. "Identifying prognostic factors in oropharyngeal carcinoma." Thesis, University of Southampton, 2014. https://eprints.soton.ac.uk/376896/.
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Dodd, R. H. "Examining the psychosocial impact of human papillomavirus oropharyngeal cancer." Thesis, University College London (University of London), 2016. http://discovery.ucl.ac.uk/1522414/.
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The causal role of human papillomavirus (HPV) in oropharyngeal squamous cell carcinoma (OSCC) has been well established. The work presented in this thesis sets out to explore the information available about HPV-OSCC and examine the psychosocial issues associated with a diagnosis of HPV-OSCC. Six studies were carried out between 2013 and 2016. Study 1 systematically reviewed the existing literature examining the psychosocial impact of HPV-OSCC in patients (n=10 studies) and current knowledge of the relationship between HPV and OSCC (n=41 studies). Study 2 was a content analysis examining the media coverage in the UK of the link between HPV and OSCC (n=112 articles). Study 3 was a qualitative study with health professionals caring for HNC patients (n=15). Study 4 was an extension of study 3, developing a survey for dissemination among health professionals working with HPV-OSCC patients (n=260). Both studies explored their experiences of and attitudes to discussing HPV with their patients, with study 4 additionally measuring knowledge of HPV-OSCC. Study 5 was a qualitative study with patients diagnosed with HPV-OSCC (n=20) and with some of these patients’ partners (n=12), examining their experiences around the diagnosis of HPV-OSCC. Study 6 involved the development of an information booklet about HPV-OSCC, based on the findings of studies 1-5. The existing literature examining the psychosocial impact of HPV-OSCC provided limited evidence about the impact of HPV in OSCC patients. Knowledge of HPV in OSCC was not well known across most populations, and the HPV-OSCC content presented in the media lacked basic facts about HPV. The increasing incidence of HPV-OSCC was a significant issue for health professionals and key messages to communicate to HPV-OSCC were found. Reactions about HPV were mixed among participants whose cancer or partners’ cancer was caused by HPV. An information booklet developed about HPV-OSCC was well received by patients and health professionals and could act as a discussion tool to provide patients with evidence-based information. De-escalation of treatment in the future may help minimise some of the negative psychosocial outcomes associated with HPV-OSCC and improve long-term functioning.
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Houston, Karla Smalley. "The Cost of Treating Human Papillomavirus-Related Oropharyngeal Cancer." ScholarWorks, 2019. https://scholarworks.waldenu.edu/dissertations/6218.
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Human papillomavirus (HPV) is a sexually transmitted infection contributing to 70% of oropharyngeal cancers in the United States. The incidence of HPV-related oropharyngeal cancers is greater in Kentucky's population than in any other state. Research has demonstrated the cost of treating oropharyngeal cancer on a national level, but little information exists as to state-specific costs. The purpose of this quantitative study was to examine radiation therapy costs for treating HPV-related oropharyngeal cancer in Kentucky in relation to age, gender, race, and insurance. A theory by Aday and Andersen was applied to explain the relationship between the independent and dependent variables. Cluster sampling was used to randomly select 130 de-identified men and women age 40-65 years who had been diagnosed with oropharyngeal cancer. The data were collected from an existing database. The study used descriptive analysis with correlational, longitudinal data to examine the relationship of categorical and continuous variables. The mean cost for radiation therapy treatment was $123,629.14 (SD= $58,697.36). The multiple regression indicated that the null hypothesis was accepted showing that the independent variables were not statistically significant predictors of the z Score of Cost Difference [F (4,122) = 0.972, p = 0.425]. The results showed no significant independent predictor variables (p > 0.05); gender [t (127) = -0.943, p = 0.348], race [t (127) = 1.378, p = 0.171], insurance type [t (127) = -1.512, p = 0.133], and age group [t (127) = -0.230, p = 0.818]). The results may contribute to positive social change in the development of cancer prevention strategies and policies.
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Waters, A. M. "A core outcome set for clinical trials in oropharyngeal cancer." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3022643/.
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The impact of randomized controlled trials is frequently diminished by disparate outcome reporting, precluding the comparison of results between trials or synthesis of data in meta-analyses. This is particularly problematic in lower incidence conditions such as oropharyngeal squamous cell carcinoma (OPSCC), where the need to synthesise data from competing trials is greater. Minimum outcome reporting standards, known as Core Outcome Sets (COS) have been shown to increase the consistency of outcome reporting between trials of comparable interventions, thus facilitating the comparison or synthesis of trial data. The objective of the work in this thesis was to identify outcomes of importance to patients, carers and healthcare professionals and define a COS for OPSCC. The methods used comprised a systematic review of OPSCC RCTs to identify the outcomes reported and establish whether there was outcomes heterogeneity as suggested by other studies; semi-structured qualitative interviews with patients and carers to establish their outcomes of importance; a Delphi Study of patients, carers and healthcare professionals, to reach consensus on the outcomes that should be included in a COS for OPSCC. The systematic review described in chapter two identified significant heterogeneity in outcome reporting; 58 outcomes were reported in 43 RCTs, only three outcomes were measured in more than 50% of studies, and only 41% of outcomes were measured in more than one study. The qualitative study identified 136 outcomes. Survival and late adverse effects of treatment are of greatest priority to patients and carers. The Delphi study successfully reached consensus on eight outcomes for inclusion in the COS. There is substantial heterogeneity in the outcomes measured in contemporary RCTs in OPSCC. Yet, there is strong consensus between stakeholder groups in the outcomes of importance. Implementation of the COS will increase the consistency of outcome reporting thus facilitating the comparison of data from competing trials and synthesis of data in meta-analyses. Further consideration must be given to ways in which the uptake of COS can be maximised to have the highest impact. The COS is applicable to trials of interventions used in current clinical practice, however the advent of new treatment strategies may require that this is reviewed and adapted.
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Wintour, Alisha M. "Evaluation of an information pamphlet for human papillomavirus positive oropharyngeal cancer patients." Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/228752/14/Alisha_Wintour_Thesis.pdf.
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This study evaluated the effectiveness of an information pamphlet designed to address common information gaps that exist for human papillomavirus positive oropharyngeal cancer patients. The study has highlighted the complex psychosocial impacts of a human papillomavirus positive oropharyngeal cancer diagnosis and has provided insight into how an informational intervention could assist patients to manage these impacts. The results contribute to the growing evidence regarding the psychosocial and information needs of human papillomavirus positive oropharyngeal cancer patients.
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Hellman, Jennifer L. "The biobehavioral relationship between pain and stress in postoperative oropharyngeal cancer patients." Connect to resource, 2009. http://hdl.handle.net/1811/37134.
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Abram, Muhammed Hanif. "The incidence of oral and oropharyngeal cancer in South Africa for the five year period 1997-2001." Diss., University of Pretoria, 2013. http://hdl.handle.net/2263/24655.
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The National Cancer Registry (NCR) of South Africa publishes pathology-based cancer incidence in the country and is the main cancer data source. The data published by the NCR have been used extensively in the development of the draft national guidelines for cancer prevention and control as well as for cancer research. The list of contributing pathology laboratories is fairly inclusive. As far as Oral Cancer is concerned, the Department of Oral Pathology, University of Limpopo, has however not submitted data to the NCR. It is therefore reasonable to assume that because of this, a large proportion of histologically diagnosed oral cancers are not reflected in the NCR. Materials and methods: Data from the National Cancer Registry and the University of Limpopo, Department of Oral Pathology for the five years 1997-2001 were combined and then filtered for sites in the oral and oropharyngeal region. Age- Standardised Incidence Rates (ASIR) and the Cumulative Lifetime Risk (LR) for males and females in the different population groups were determined. Conclusion: It is possible that the total ASIR for oral and oropharyngeal cancer has increased in South Africa. The incidence of oral and oropharyngeal cancer in individuals below the age of 45 years in South Africa is higher than the global average.Dissertation (MChD)--University of Pretoria, 2013.
Oral Pathology and Oral Biology
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Holzhauser, Stefan. "Effect of ionising radiation on HPV-positive and HPV-negative oropharyngeal cancer cell lines." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/120510/.
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In recent decades, the incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) has increased world-wide. Overall, HPV-positive OPSCC patients respond better to treatment (increased survival rate) compared to HPV-negative patients. This might be partially associated with a deficiency in repair of double-strand DNA breaks, and/or with residual p53 activity in HPV-positive tumours. However new studies, specific to HPV-positive OPSCC, are limited due to the low number of relevant OPSCC in-vitro models. The general aims of this study were to develop new HPV-positive OPSCC cell lines and use them, together with established OPSCC cell lines, to investigate responses to ionising radiation (IR). These experiments were intended to test that HPV-positive OPSCC cell lines were more sensitive to IR than HPV-negative OPSCC cell lines. Two novel OPSCC cell lines, one HPV-positive and one HPV-negative, were derived and characterised. The HPV-positive OPSCC cell lines demonstrated greater variation in radio-sensitivity compared to HPV-negative OPSCC cell lines. However, radio-sensitivity was not associated with p53 accumulation and/or cell cycle arrest. All HPV-positive OPSCC cell lines showed G2 arrest after IR, but so did several HPV-negative lines. The mRNA sequencing data confirmed expression of HPV oncogenes and integration of HPV DNA into the host genome, with an increase of integration sites after IR. Comparison of irradiated HPV-positive and HPV-negative cell lines did not show consistent differences in gene expression associated with DNA repair. The transcription of DNA repair factors did not correlate with radio-sensitivity within the HPV-positive cell lines. The study was successful in generating and characterising new OPSCC cell lines but did not find evidence that the better prognosis of HPV-positive tumours is associated with defects in DNA repair. This suggests that additional mechanisms may be responsible for the improved prognosis of HPV-positive OPSCC patients following treatment.
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Schache, Andrew G. "The molecular and clinical implications of human papillomavirus-16 mediated oropharyngeal squamous cell carcinoma." Thesis, University of Liverpool, 2013. http://livrepository.liverpool.ac.uk/13433/.
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The last three decades have seen a fundamental change in the profile of oropharyngeal squamous cell carcinoma (OPSCC) within the developed world. The incidence of OPSCC attributable to tobacco and alcohol exposure has been gradually declining whilst Human papillomavirus (HPV)-related OPSCC has seen a rapid increase. Detection of High Risk HPV has profound prognostic significance as it correlates with both a disease-specific and an overall survival advantage. The stringency of testing, both in terms of diagnostic and prognostic capacity is therefore of increasing importance. This study sought to define the relative abilities of the diagnostic tests presently available in clinical practice and to explore the potential of a novel test in reaching the improved stringency called for by the clinical community. Diagnostic biomarkers with prognostic capacity, such as those utilised in defining HPV status in this research have been well described, however, despite HPV positive OPSCC being biologically distinct from HPV negative malignancy, predictive biomarkers defining the transition from persistent to transforming infection are yet to be forthcoming. A lack of an apparent premalignant state, akin to that seen in HPV-mediated cervical malignancy has restricted biomarker recognition. This research aimed to better define the epigenetic state and clarify the impact of viral integration for the virus and host in HPV positive OPSCC. Although detectable epigenetic alterations, within the genome of the virus and that of the host, were capable of providing an improved description of this burgeoning disease state, they fell short of providing clinically relevant biomarkers. It was however demonstrated that the previously held concept of preferential E2 cleavage during viral integration as a means to disrupt gene expression, is overstated and the model persists to the exclusion of other viral and host genome disruptions. A paradigm shift may be necessary in HPV positive OPSCC to an understanding of obligatory viral integration, the significance of which however, is yet to be fully elucidated.
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Ährlund-Richter, Andreas. "Analysis of somatic mutations in papillomavirus positive tumours from younger and older oropharyngeal cancer patients." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-12853.
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ABSTRACT Background: Human Papilloma Virus positive (HPV+) Oropharyngeal Squamous Cell Carcinoma (OSCC), dominated by tonsillar cancer (TSCC) and base of tongue cancer (BOTSCC) has low mutation-frequency and better survival for younger than older patients.Aim: To examine if HPV+ TSCC and BOTSCC have distinct gene-mutation profiles, for 50 often-mutated genes in cancer, in younger compared to older patients and to test and compare different variant callers to get a deeper understanding of the data.Materials and methods: DNA had previously been extracted from 299 formalin-fixed-paraffin-embedded (FFPE) tumor biopsies and 13 normal samples, and sequenced on the Ion Proton sequencer, a NGS (Next-Generation Sequencing) platform. Alignment and variant calling had been performed via the Ion Torrent Suite software v5 (ITS), and Torrent Variant Caller (TVC).UPPMAX, a High-Performance-Computational cluster (HPC) at Uppsala University was used for storing and computing of the sequenced data. Parallel-processing was used to optimize repetitive steps, saving days of computation time. The descriptive analysis, graphical data representations, and more in-depth analysis, were done in R.Initially, variant calling was performed for 13 tumor/normal paired samples using the novel MuTect2 software from the Genome Analysis Toolkit (GATK) toolset. Variant annotation and statistical analysis was performed on all the 13 paired sequenced samples, using SnpEff. Due to a poor overlap between the above MuTect2 and TVC, after adequate filtering TVC, MuTect, Strelka and VarScan2 were also utilized for comparison.Result and Conclusion: Having only 13 normal samples, normal-tumor paired variant calling to distinguish germ line and somatic variants could not be performed. To obtain an approximation of the amount of germline variation in our cohort, additional variant callers were used for the tumor normal pairs. The data obtained with the TVC caller formed the basis for further analysis of the tumor samples.Notably, comparisons of TVC with MuTect2 output revealed major discrepancies and limited overlap. However, when comparing MuTect2 with MuTect, Strelka, or VarScan 2 regarding overlaps with TVC – the overlap were still limited, but higher degrees of overlaps were disclosed between Strelka, MuTect and MuTec2, indicating that MuTect2 was a successful further development and successor of MuTect.Evidence for presence of distinct gene-mutation profiles correlating to age could not be obtained in the analyzed tumor cohort with the software tool kits applied. Statistical analysis using Wilcoxon-Mann Whitney test did not support a hypothesis of distinct age related mutations for any of the 50 genes analyzed in this tumor cohorts.The highest p-value for the Wilcoxon-Mann Whitney test was for the gene APC, at p ~ 0.054 hints at a possible connection. However, more extensive research with more samples sequenced is necessary to confirm or reject this correlation.
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Almarzouki, Hani. "Human Papillomavirus (HPV) infection and Erythropoietin Receptors (EPoR) expression as prognostic indicators in oropharyngeal cancer." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=119496.
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Background: Human papillomavirus (HPV) infection is recognized as an independent risk factor for squamous cell carcinomas (SCCs) of the head and neck, and the presence of HPV DNA is associated with a better prognosis. Recent evidence indicates a broader role for erythropoietin via binding and activation of its receptor (EpoR), which is present in many neoplastic non-hematopoietic cells. The expression of EpoR in cancer may represent a selection process that permits cancer cells to survive in an unfavorable microenvironment and may indicate aggressive cancer cell behavior. EpoR is variably expressed in head and neck cancer cells and could independently predict a poorer treatment response. Objectives: 1. To determine HPV status and the frequency of EpoR expression in archived biopsy specimens obtained from patients with oropharyngeal SCCs. 2. To evaluate whether the EpoR status affects survival and whether this putative effect is influenced by HPV status. Methods: A retrospective cohort study was conducted by reviewing the charts of 97 patients with oropharyngeal SCCs treated with primary curative intent radiation therapy at the McGill University Health Center, from 2000 to 2009. Eligible patients had to have archived tissue samples available for HPV and EpoR analysis. HPV DNA testing and typing was done using a standard polymerase chain reaction (PCR) protocol. EpoR status was determined by immunohistochemistry using rabbit polyclonal anti-EpoR staining. Stained sections were analyzed by 2 independent examiners by conventional light microscopy. A score product of 0-300 was determined for each patient by multiplying the percentage of neoplastic cells staining for EpoR (0-100%) and the intensity of the EpoR staining expressed from 0 to 3. Results: The median age was 62 years (range: 43–83). HPV status was positive in 74% of patients and this was significantly higher in patients aged ≤65 years, p=0.023. Patients with a significant smoking history (>10 pack-years) and drinking history (>4 drinks/week) were significantly more likely to be HPV negative, p= 0.041 and 0.0001 respectively. On Cox regression analysis, HPV positivity was associated with a 29% reduction in risk of death (Hazard Ratio (HR)=0.71; 95% Confidence Interval (CI): 0.34-1.49), albeit non-significantly. EpoR status was positive in 27% of patients and was associated with a non-significant 23% increase in risk of death (HR=1.23; 95%CI: 0.59-2.56). Patients who were HPV positive and EpoR negative had a non-significant 33% reduction in risk of death (HR=0.67; 95%CI: 0.29-1.56).Conclusion: This study demonstrates a trend indicating that HPV and EpoR status correlate with survival. This trend persists when patients are divided into low, intermediate and high-risk groups based on their HPV/EpoR status. The lowest risk group appears to consist of patients, which are HPV positive and EpoR negative. To the best of our knowledge this is the first study to discuss the relation of EpoR and survival in head and neck cancer.Contexte: Le virus du papillome humain (VPH) est reconnu comme un facteur de risque indépendant pour les carcinomes épidermoïdes (CE) de la tête et du cou. De plus, la présence de l'ADN du VPH est associée à un meilleur pronostic. Des recherches récentes indiquent un plus grand rôle de l'érythropoïétine via une une activation de son récepteur (EpoR), qui est présent dans de nombreuses cellules non-hématopoïétiques néoplasiques. L'expression de EpoR dans un cancer peut représenter un processus de sélection qui permet aux cellules cancéreuses de survivre dans un environnement défavorable et peut aussi indiquer un comportement agressif des cellules cancéreuses. EpoR est variablement exprimé dans les cancers de la tête et du cou et pourrait prédire de façon indépendante une réponse plus faible aux traitements offerts aux patients. Objectifs: 1. Pour déterminer le statut VPH des cellules et la fréquence de l'expression du récepteur EpoR dans des biopsies obtenues de patients atteints du cancer épidermoïde oropharyngé. 2. Pour évaluer si la présence d'EpoR affecte la survie et si cet effet négatif est influencé par le statut VPH des cellules. Méthodes: Une étude rétrospective a été menée en examinant les dossiers de 97 patients atteints du cancer épidermoïde oropharyngé traités par radiothérapie comme intention curative au Centre universitaire de santé McGill, de 2000 à 2009. Les patients éligibles devaient avoir archivé des échantillons de tissus disponibles pour l'analyse VPH et EpoR. L'analyse de la présence du VPH a été effectuée en utilisant une réaction standard en chaîne par polymérase (PCR). La présence du récepteur EpoR a été déterminée par immunohistochimie en utilisant des marqueurs polyclonaux colorants anti-EpoR obtenus chez les lapins. Les sections de pathologie ont été analysées par 2 examinateurs indépendants par la microscopie optique conventionnelle. Un score de 0 à 300 a été déterminé pour chaque patient en multipliant le pourcentage de cellules néoplasiques contenant l'EpoR (0 à 100%) et l'intensité de la coloration de l'EpoR exprimée de 0 à 3. Résultats: L'âge médian était de 62 ans (extrêmes: 43-83). Le statut VPH a été positif chez 74% des patients. Ceci était significativement plus élevé chez les patients âgés ≤ 65 ans, p = 0,023. Les patients ayant des antécédents de tabagisme importants (> 10 paquet-années) et d'alcoolisme (> 4 verres / semaine) étaient significativement plus susceptibles d'être VPH négatif, p = 0,041 et 0,0001 respectivement. En analyse de régression de Cox, la présence de VPH était associé à une réduction de 29% du risque de décès (Hazard Ratio (HR) = 0,71, Intervalle de confiance (IC) 95%: 0,34 à 1,49), mais de façon non significative (p >0.05). Le statut EpoR était positif chez 27% des patients et a été associé à une augmentation non significative de 23% du risque de décès (RR = 1,23, IC 95%: 0,59 à 2,56). Les patients qui étaient positifs pour le VPH et négatifs pour l'EpoR avaient une réduction non significative de 33% du risque de décès (RR = 0,67, IC 95%: 0,29 à 1,56).Conclusion: Cette étude démontre une tendance qui indique que le VPH et le statut EpoR ont une corrélation avec la survie. Cette tendance persiste lorsque les patients sont divisés en sous-groupes (faible, intermédiaire et haut risque) en fonction de leur statut VPH / EpoR. Le groupe avec le plus faible risque de décès sont les patients avec le statut de VPH positif et EpoR négatif. Au meilleur de nos connaissances, cette étude est la première à examiner la relation entre l'EpoR et la survie chez les patients avec le cancer de la tête et du cou.
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Ronchin, Philippe. "Les tumeurs oropharyngees : experience du centre oscar lambret sur 10 ans (1974-1983)." Lille 2, 1993. http://www.theses.fr/1993LIL2M141.
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Lam, Wai-hung, and 林偉雄. "The current situation of human papillomavirus (HPV) associated oropharyngeal cancer : a multi-institutional cohort study in Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206586.
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Despite the advance in modern oncology, there was limited improvement over the survival outcome of head and neck cancers. Until the discovery of the etiological association between Human Papillomavirus (HPV) and oropharyngeal cancer, an accelerated evolution in the field of head and neck oncology began. This viral-related tumor has ignited tremendous effort in American and European countries to explore the optimal treatment approaches. In contrast, the paucity of comprehensive and robust studies commonly exists in many Chinese and Asian countries. Little is known about the current situation of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) in Hong Kong.
This retrospective local multi-institutional study attempted to explore the HPV-associated OPSCC in Hong Kong from various aspects, including demographics, risk factors, clinical and histological features, molecular profile, as well as clinical outcomes. Finally, attempts were made to determine any predictive factors to stratify high-risk patients in this distinct disease entity and explore the most appropriate detection algorithm of the biologically active HPV infection in our locality.
With the support from the Hong Kong Cancer Registry and nine public hospitals, 141 (43.3%) of 326 newly diagnosed OPSCC in the whole population of Hong Kong between 2005 and 2009 were recruited. Inclusion criteria were histologically proven OPSCC with tumor specimens available for prospective laboratory tests. Those with non-SCC, non-oropharyngeal in origin and incomplete clinical records were excluded. Prospective HPV PCR and genotyping, and immunohistochemical staining with p16, p53, cyclin D1 and HER-2 were performed. Univariate and multivariate analyses were performed to assess the correlations between various parameters and HPV-associated OPSCC.
Epidemiologically, based on the combined positivity in HPV PCR and p16, the prevalence of HPV-associated OPSCC was 22%. Thirty (96.8%) of thirty one were HPV-16, the remaining one was HPV-18. In the univariate analysis, this cancer directly correlated with female gender (p=0.014), younger age (p=0.012), non-smoker (p=0.02), non-drinker (p=0.06) and early primary tumor (p=0.001). Histologically, basaloid differentiation (p<0.001), non-keratinization (p=0.007) and high tumor infiltrating lymphocyte (TIL) level (p<0.001) showed significant correlations. A distinct molecular profile was identified, with p16 positivity noted in all cases (p<0.001), few of p53 (p<0.001) and cyclin D1 positivity (p<0.001) and absence of HER2 over-expression.
Significantly superior prognosis was demonstrated in HPV-associated OPSCC. The 5-year overall and disease specific survivals were 67.0% and 88.6% compared with 27.8% (p<0.001) and 41.3% (p<0.001) in the non-viral counterpart respectively. Other good prognostic factors identified for OS and DSS included early primary disease (T1/T2) (p=0.02; p=0.001), absence of distant metastasis (both p<0.001), high TIL level (both p<0.001), p16-positivity (p=0.002; p=0.003), non-smoker (p=0.021; p=0.014). In the multivariate analysis, the HPV-associated tumor (HR: 0.28; 95% CI: 0.08 – 0.93; p=0.038), early primary tumor (HR: 0.52; 95% CI 0.30 – 0.89; p=0.017) and absence of distant metastasis (HR=0.15 95% CI: 0.07 – 0.3; p<0.001) were associated with lower risk of death from any causes after controlling other confounding factors.
Most importantly, high TIL level in HPV-associated OPSCC patients was associated with 89% (HR: 0.11; 95% CI: 0.02 – 0.61; p=0.012) lower risk of death from any causes than those with low TIL level, but not present in non-HPV counterpart. In addition, either HPV PCR complemented with typical high-risk genotyping results or p16 IHC positivity complemented with HPC PCR positivity using specific designed primers were two reasonably sensitive and specific detection algorithms based on the local genotypic distribution of this disease.
In summary, this is the first most comprehensive and robust local study indicating the importance of HPV-associated OPSCC in Hong Kong. It successfully illustrated various distinctive characteristics of this viral-related cancer. Additionally, it has suggested a potential predictor to identify the minority with more aggressive diseases and the most effective laboratory detection algorithms in this locality. It definitely facilitates the next step in exploring this disease via larger and prospective trials in coming future.published_or_final_version
Surgery
Master
Master of Medical Sciences
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Sahlin, Maria. "Sväljningssvårigheter hos patienter opererade för munhålecancer : en litteraturstudie." Thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-168213.
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Syftet med denna litteraturstudie var att belysa sväljningssvårigheter hos patienter som genomgått kirurgisk behandling på grund av munhålecancer genom att undersöka vad som bidrar till sväljningssvårigheter, hur patienterna upplever sväljningen samt hur vårdpersonalen kan hjälpa dessa patienter. Studien baserades på 12 vetenskapliga artiklar som söktes fram i databaserna PubMed och Cinahl. Resultatet indelades utifrån vilket metodologiskt tillvägagångssätt som använts i studierna, videofluoroskopi respektive frågeformulär. Förekomst och resektion av tumör i orofarynx, särskilt tungbasen, gav större sväljningsdysfunktion jämfört med orala tumörer i flera av videofluoroskopistudierna. När frågeformulär användes för att undersöka patienternas självupplevda sväljning sågs att strålbehandling var en viktig negativ faktor för sväljningen. I flera av studierna sågs att större resektionstorlek/tumörstorlek eller ett avancerat sjukdomsstadie hade negativ inverkan på sväljningen. Aspekter av munfunktionen rankades som mest betydande av 12 viktiga funktioner i en studie, med sväljningen på fjärde plats. I en studie som undersökt livskvalitet relaterad till sväljningssvårigheter var ”tid för ätande”, ”problem att tugga”, ”problem med mat som fastnar i munnen” de faktorer som gav lägst livskvalitet. Vid sökning efter studier som kunde svara på vilka åtgärder omvårdnadspersonal kan tillämpa för att hjälpa munhålecanceropererade patienter med sväljningssvårigheter framkom ingen relevant studie.The aim of this literature review was to illuminate swallowing difficulties in oral and oropharyngeal cancer patients treated with surgery by studying which factors contribute to swallowing difficulties, how these patients experience their swallowing and how nursing staff can assist them. The study was based on 12 research articles. The literature search was performed in the PubMed and Cinahl databases. The result was subdevided on the basis of the methods used in the studies, videofluoroscopy and questionnaires. The presence and resection of tumours of the oropharynx, in particular of the base of the tongue, resulted in more severe swallowing dysfunction compared to tumours of the oral cavity in several of the videofluoroscopic studies. Self-assessment questionnaires showed that radiation therapy had a mayor negative effect on swallowing. In several studies large tumours/resections and an advanced stage had a negative impact on swallowing. In one study aspects of mouth function was ranked to be the most important of 12 important issues, swallowing coming in fourth place. One study that evaluated quality of life related to swallowing after surgery, found that the main factors effecting the quality of life were “eating duration”, “problems chewing” and “food sticking in your mouth”. In the search for studies answering the question of what actions nursing staff can apply in caring of oral and oropharyngeal cancer patients with swallowing difficulties after surgery no relevant study was found.
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Brown, Elizabeth M. "Biologically guided adaptive radiotherapy treatment planning for virally-mediated head and neck cancer." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/98899/1/Elizabeth_Brown_Thesis.pdf.
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This thesis developed predictive models and risk profiles for pre-treatment identification of suitable adaptive radiotherapy candidates, from a cohort of oropharyngeal and nasopharyngeal cancer patients. This unique prospective approach could facilitate effective implementation of head and neck cancer adaptive radiotherapy into radiotherapy departments in Australia and internationally, through forward planning and appropriate resource allocation. Predicting those patients more likely to need adaptive radiotherapy in an efficient and judicious manner provides numerous benefits to radiotherapy departments across the world and ultimately, the patients under our care.
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Al-Sahaf, Sarmad. "Investigating the HPV-positive & HPV-negative oropharyngeal cancer tumour microenvironment in vivo and in vitro." Thesis, University of Sheffield, 2018. http://etheses.whiterose.ac.uk/22533/.
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Human papillomavirus (HPV) is now recognised as a major aetiological agent in the pathogenesis of oropharyngeal carcinoma (OPC). HPV-positive tumours are associated with better outcomes compared to HPV-negative tumours, possibly due to differences in their aetiology, immune responses and/or the tumour microenvironment. Increased numbers of tumour-associated leukocytes have been observed in many cancers including OPC, with variable influence on prognosis depending on the leukocyte subpopulation investigated. Whether, HPV-status influences leukocyte recruitment to OPC remains unknown. The main aim of this study was to examine if differences exist in the immune responses between HPV-positive compared to HPV-negative OPC by examining levels of infiltrated leukocyte sub-populations, and to further determine the molecular mechanisms driving leukocyte recruitment into these two distinct forms of tumours. Immunohistochemical staining of HPV-positive (n=40) and HPV-negative (n=19) OPC biopsies, followed by survival analysis showed that individuals with HPV displayed a distinct survival advantage. In terms of leukocyte abundance, HPV-negative OPC contained significantly (P < 0.05) more neutrophils than HPV-positive tumours, whilst there was no difference in macrophage or T cell abundance between the two tumours except in the low expressive cases. A subsequent in vitro study examined differences in the chemoattractant capacity of HPV-positive and HPV-negative OPC cell lines to determine if these factors were implicated in the neutrophil, macrophage and T cell recruitment observed in vivo. Gene and protein expression analysis demonstrated that both monocultures of HPV-positive and HPV-negative cell lines, along with normal tonsillar fibroblasts (NTF), expressed low chemokine levels, whilst NTF cultured with conditioned medium from HPV-negative OPC cells expressed significantly higher levels of all chemokines tested compared to NTF incubated with the medium from HPV-positive OPC cell lines. HPV-negative OPC cell lines expressed the pro-inflammatory cytokines IL-1α & β mRNA whereas HPV-positive cells did not, and NTF constitutively expressed IL-1R. Pre-treatment with the IL-1R antagonist, Anakinra, or siRNA to IL-1R1 significantly reduced chemokine secretion from NTF stimulated with conditioned medium from HPV-negative tumour cells or recombinant IL-1β (P < 0.05). Similar data was obtained when cells were cultured all together in a 3D-model of OPC. In addition, in a 3D co-culture model, treatment with Anakinra significantly reduced the chemokines and number of infiltrating leukocytes into the model compared to untreated 3D cultures. Taken together, these data suggest that secretion of chemokines is driven by the interaction between HPV-negative OPC cells and stromal tonsillar fibroblasts through an IL-1/IL-1R-mediated mechanism that is less prominent within the HPV-positive tumour microenvironment. These observations may explain differences in leukocyte sub-populations recruited to HPV-positive versus negative OPC and indicate that HPV-status is a key determinant in controlling the inflammatory tumour microenvironment. Controlling leukocyte infiltration into HPV-negative OPC using Anakinra may be of potential clinical benefit.
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Shay, Keegan P. "Evaluating the use of neighborhoods for query dependent estimation of survival prognosis for oropharyngeal cancer patients." Thesis, University of Iowa, 2019. https://ir.uiowa.edu/etd/6854.
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Oropharyngeal Cancer diagnoses make up three percent of all cancer diagnoses in the United States per year. Recently, there has been an increase in the incidence of HPV-associated oropharyngeal cancer, necessitating updates to prior survival estimation techniques, in order to properly account for this shift in demographic. Clinicians depend on accurate survival prognosis estimates in order to create successful treatment plans that aim to maximize patient life while minimizing adverse treatment side effects. Additionally, recent advances in data analysis have resulted in richer and more complex data, motivating the use of more advanced data analysis techniques. Incorporation of sophisticated survival analysis techniques can leverage complex data, from a variety of sources, resulting in improved personalized prediction. Current survival prognosis prediction methods often rely on summary statistics and underlying assumptions regarding distribution or overall risk.
We propose a k-nearest neighbor influenced approach for predicting oropharyngeal survival outcomes. We evaluate our approach for overall survival (OS), recurrence-free survival (RFS), and recurrence-free overall survival (RF+OS). We define two distance functions, not subject to the curse of dimensionality, in order to reconcile heterogeneous features with patient-to-patient similarity scores to produce a meaningful overall measure of distance. Using these distance functions, we obtain the k-nearest neighbors for each patient, forming neighborhoods of similar patients. We leverage these neighborhoods for prediction in two novel ensemble methods. The first ensemble method uses the nearest neighbors for each patient to combine globally trained predictions, weighted by their accuracies within a selected neighborhood. The second ensemble method combines Kaplan-Meier predictions from a variety of neighborhoods. Both proposed methods outperform an ensemble of standard global survival predictive models, with statistically significant calibration.
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Jones, Gieira Shaquae. "RACIAL DISPARITIES IN HUMAN PAPILLOMAVIRUS PREVALENCE IN HEAD AND NECK CANCER PATIENTS: AN INTERNATIONAL POOLED AND META-ANALYSIS." Master's thesis, Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/216588.
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Public HealthM.S.
Head and neck cancer (HNC) is one of the top ten cancers in the world, and is caused by tobacco use, alcohol consumption and Human Papillomavirus (HPV). HPV associated HNC patients have improved survival rates compared to non -HPV associated HNC patients. This improved survival is due to HPV- positive tumors favorable response to chemotherapy and radiation. The literature has shown that there is a racial disparity in survival rates between Caucasians and African Americans, with African Americans having poorer survival rates. The aim of this study is to determine if the racial disparity among HNC patients is due to a difference in HPV prevalence between races. HPV prevalence in HNC was assessed by a meta-analysis of published articles (30/247) that reported race specific HPV prevalence. We also conducted a pooled analysis in which authors that assessed HPV in HNC were invited to submit their datasets. Meta-pooled prevalence estimates revealed that 20% of African American HNC patients had HPV-positive tumors, compared to 44% in Caucasians. However for both African American HNC patients and Caucasian HNC patients there was low to moderate heterogeneity between the studies (Q-test p-value = p < 0.001, I2 = 18.87%, and p= 0.008. I2 =65.47% respectively). The prevalence of HPV in African Americans was 60% and in Caucasians it was 39%. African Americans had a risk of oropharyngeal cancer that was no different from Caucasians (OR: 1.38, 95% CI: 0.53-3.62) but had an increased risk of death from oropharyngeal cancer (HR: 2.39, 95% CI 1.03-5.55) compared to Caucasians. The results of the pooled analysis does not support the concept that African Americans HNC patients have a lower prevalence of HPV, but substantiates the notion that African Americans have worse survival than Caucasians. However, these are preliminary results as the pooled analysis is still being conducted, the inclusion of more datasets in the analysis could alter these preliminary findings.
Temple University--Theses
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Bastos, Daniela Brito. "Plasma catecholamines levels in oral and oropharyngeal cancer patients and their associations with clinicopathological variables and anxiety symptoms /." Araçatuba, 2017. http://hdl.handle.net/11449/151501.
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Orientador: Daniel Galera BernabéCoorientador: Glauco Issamu Miyahara
Banca: Dulce Elena Casarini
Banca: Eder Ricardo Biasoli
Resumo: Objetivos: As catecolaminas podem regular diversos efeitos biológicos resultantes do estresse crônico. Estudos demonstram que as catecolaminas podem influenciar a progressão do câncer. No entanto, pouco se sabe sobre o perfil de secreção das catecolaminas em pacientes com câncer de cabeça e pescoço (CCP) e sua associação com as variáveis clinicopatológicas e psicológicas. O presente estudo investigou os níveis plasmáticos pré-tratamento das catecolaminas norepinefrina (NE) e epinefrina (E) em pacientes com câncer de boca e orofaringe e em pacientes com leucoplasia bucal, bem como sua associação com as variáveis clinicopatológicas, biocomportamentais e os sintomas de ansiedade. Pacientes e métodos: Um total de 71 pacientes com carcinoma espinocelular (CEC) de boca, 22 pacientes com CEC de orofaringe e 32 portadores de leucoplasia bucal foram submetidos à coleta de amostras de sangue. Os níveis plasmáticos das catecolaminas NE e E foram mensurados por meio de Cromatografia Líquida de Alta Eficiência com detecção eletroquímica (CLAE-ED) e os níveis psicológicos de ansiedade foram mensurados pelo Inventário de Ansiedade de Beck (IAB). As diferenças nos níveis hormonais entre os grupos foram avaliadas pelo teste ANOVA e análises univariadas e regressões múltiplas foram realizadas para avaliar as associações dos níveis hormonais com as variáveis clinicopatológicas, biocomportamentais e psicológicas. Resultados: As concentrações plasmáticas de NE e E foram significativamente maiores... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Background: Catecholamines may regulate several biological effects resulting from chronic stress. Studies have shown that stress-related catecholamines may affect cancer progression. However, little is known about catecholamines secretion profile in head and neck cancer squamous cell carcinoma (HNSCC) patients and its association with clinicopathological and psychological variables. The present study investigated the pre-treatment plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in patients with oral and oropharyngeal SCC and patients with oral leukoplakia, as well as their associations with clinicopathological and biobehavior variables and anxiety symptoms. Patients and methods: A total of 71 patients with oral SCC, 22 patients with oropharyngeal SCC and 32 patients with oral leukoplakia were submitted to blood samples. Plasma levels of NE and E were measured by High Performance Liquid Chromatography with electrochemical detection (HPLC-ED) and psychological anxiety levels were measured by the Beck Anxiety Inventory (BAI). Differences in hormone levels among the groups were analyzed by ANOVA test. Univariate and multiple regression analyzes were performed to evaluate the associations of hormonal levels with clinicopathological, biobehavior and psychological variables. Results: Plasma NE and E concentrations were significantly higher in patients with oral and oropharyngeal cancer than oral leukoplakia patients (p<0.05). Oral SCC patients showed NE levels (462.03±47.53 pg/mL) about six times and nine times higher than patients with oropharyngeal SCC (74.46±12.52 pg/mL) and oral leukoplakia (51.69±6.28 pg/mL), respectively. Plasma NE and E levels were positively correlated in patients with oral SCC (p=0.0011), but not in the oropharyngeal SCC and oral leukoplakia groups. Multiple...
Mestre
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Zdilar, Luka. "Evaluating the effect of right-censored endpoint transformation for dimensionality reduction of radiomic features of oropharyngeal cancer patients." Thesis, University of Iowa, 2018. https://ir.uiowa.edu/etd/6346.
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Radiomics is the process of extracting quantitative features from tomographic images (computed tomography [CT], magnetic resonance [MR], or positron emission tomography [PET] images). Thousands of features can be extracted via quantitative image analyses based on intensity, shape, size or volume, and texture. These radiomic features can then be used in combination with demographic, disease, and treatment indicators to increase precision in diagnosis, assessment of prognosis, and prediction of therapy response.
However, for models to be effective and the analysis to be statistically sound, it is necessary to reduce the dimensionality of the data through feature selection or feature extraction. Supervised dimensionality reduction methods identify the most relevant features given a label or outcome such as overall survival (OS) or relapse-free survival (RFS) after treatment. For survival data, outcomes are represented using two variables: time-to-event and a censor flag. Patients that have not yet experienced an event are censored and their time-to-event is their follow up time. This research evaluates the effect of transforming a right-censored outcome into binary, continuous, and censored aware representations for dimensionality reduction of radiomic features to predict overall survival (OS) and relapse-free survival (RFS) of oropharyngeal cancer patients. Both feature selection and feature extraction are considered in this work.
For feature selection, eight different methods were applied using a binary outcome indicating event occurrence prior to median follow-up time, a continuous outcome using the Martingale residuals from a proportional hazards model, and the raw right-censored time-to-event outcome. For feature extraction, a single covariate was extracted after clustering the patients according to radiomics data. Three different clustering techniques were applied using the same continuous outcome and raw right-censored outcome.
The radiomic signatures are then combined with clinical variables for risk prediction. Three metrics for accuracy and calibration were used to evaluate the performance of five predictive models and an ensemble of the models. Analyses were performed across 529 patients and over 3800 radiomic features. The data was preprocessed to remove redundant and low variance features prior to either selection or clustering. The results show that including a radiomic signature or radiomic cluster label predicts better than using only clinical data. Randomly generating signatures or generating signatures without considering an outcome results in poor calibration scores. Random forest feature selectors with the continuous and right-censored outcomes give the best predictive scores for OS and RFS in terms of feature selection while hierarchical clustering for feature extraction gives similarly predictive scores with compact representation of the radiomic feature space.
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Santos, Ingrid da Silva [UNESP]. "Absence of human papillomavirus in fresh tissue of oral cavity and oropharynx cancer in patients from the northwest region of São Paulo, Brazil." Universidade Estadual Paulista (UNESP), 2017. http://hdl.handle.net/11449/150980.
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Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM)
Evidências sugerem que o papilomavírus humano (HPV) está associado com um subgrupo de carcinomas de células escamosas da cabeça e pescoço (HNSCC). No entanto, a prevalência do HPV varia substancialmente dependendo do local anatômico e da região geográfica estudada. Aqui, nosso objetivo foi investigar a prevalência do HPV em amostras de tecido fresco de pacientes brasileiros com carcinoma de células escamosas (CEC) de boca e orofaringe combinando dois métodos confiáveis para a detecção do HPV. Foram recrutadas trinta e seis amostras de tecido fresco provenientes de CEC de boca (n= 27) e orofaringe (n= 9) para análises. As características sociodemográficas, estilo de vida e clinicopatológicas foram coletadas através dos prontuários. O DNA do HPV foi detectado por dois métodos: reação em cadeia da polimerase (PCR) em tempo real através de ensaio qualitativo de presença ou ausência do HPV-16, e testado para 37 genótipos usando Linear Array. A amplificação do gene β -globina funcionou como controle interno positivo para a análise do DNA em todas as amostras. O DNA do HPV não foi detectado em nenhum dos casos de amostras de tecido de pacientes com CEC em ambos os métodos utilizados. A ausência do HPV observada em nosso estudo pode sugerir que este não é um fator de risco prevalente nos CECs de boca e orofaringe nesta região geográfica. Os fatores de risco clássicos para o desenvolvimento desses tumores parecem ser ainda a principal causa nessa população brasileira. Investigações detalhadas do estilo de vida com maior amostragem precisam ser melhor exploradas para compreensão da baixa prevalência encontrada.
Evidence suggests that human papillomavirus (HPV) is associated with a subgroup of squamous cell carcinomas of the head and neck (HNSCC). However, the prevalence of HPV varies substantially depending on the anatomical site and geographic region studied. Here, our goal was to investigate the prevalence of HPV in fresh tissue samples from Brazilian patients with squamous cell carcinoma (SCC) of the oral cavity and oropharynx by combining two reliable methods for the detection of the HPV DNA. We recruited thirty-six fresh tissue samples from SCC of the oral cavity (n= 27) and oropharynx (n= 9) for analysis. The sociodemographic, lifestyle and clinicopathological characteristics were obtained from individual medical records. HPV DNA was detected by two methods: real-time polymerase chain reaction (PCR) through the qualitative assay of presence or absence for HPV-16, and tested for 37 genotypes by the Roche Linear Array. Amplification of the β-globin gene functioned as a positive internal control for DNA analysis in all samples. HPV DNA was detected in none of the tissue samples from patients with SCC in both methods. The absence of HPV observed in our study may suggest that this is not a prevalent risk factor in SCC of the oral cavity and oropharynx in this geographical region. The classic risk factors for the development of these tumors seem to be still the main cause in this Brazilian population. Detailed investigations of lifestyle with larger sample needs to be better explored to understand the low prevalence found.
FAPEAM: 120/2015
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Shepherd, Karen Louise. "An investigation of the experience of patients with oral and oropharyngeal cancer : from diagnosis to three months post treatment." Thesis, University of Nottingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272360.
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Smith, Eric A. B. S. "DEK is a Homologous Recombination DNA Repair Protein and Prognostic Marker for a Subset of Oropharyngeal Carcinomas." University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin150480040523791.
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Qian, Xu [Verfasser]. "ALDH1-positive cancer stem-like cells enrich in nodal metastases of oropharyngeal squamous cell carcinoma independently of HPV-status / Xu Qian." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2013. http://d-nb.info/1043197427/34.
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Lim, Yen Kai. "Oral microbiome: A novel biomarker for oral cavity and oropharyngeal cancer detection and a potential surveillance tool for post-treatment monitoring." Thesis, Queensland University of Technology, 2019. https://eprints.qut.edu.au/130735/1/Yen%20Kai_Lim_Thesis.pdf.
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This project is a pilot proof of concept aimed at investigating the human oral microbiome profile changes in healthy individual and cancer patient using saliva samples. The microbiome changes are associated with tumorigenesis and can be used as a non-invasive biomarker to detect and monitor oral cancer. The promising data demonstrates the feasibility of tailored medicine for oral cancer patients to improve survival and quality of life. In addition, these findings also serve as the first step towards understanding the functional roles of human oral microbiome in cancers.
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Dwivedi, Raghav Chandra. "A comprehensive assessment of funtional outcomes and their impact on the quality of life in surgically treated oral and oropharyngeal cancer patients." Thesis, Institute of Cancer Research (University Of London), 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.536234.
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Dugoni, Meredith L. "Role of the Pediatric Dental Provider in Human Papillomavirus (HPV) Education." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4733.
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Purpose: This study investigates knowledge about HPV and examines if pediatric dental providers should include HPV education for guardians of patients 10-18 years.
Methods: Legal guardians of 10-18 year-old patients of the Virginia Commonwealth University Pediatric Dental Clinic were enrolled in this prospective cohort study. Participants completed a baseline survey, were provided HPV education, completed an initial follow-up survey, and then completed a 6-month follow-up survey.
Results: A total of 54 participants completed the baseline and initial follow-up surveys and 17 completed the 6-month follow-up survey. The average number of correct responses was 3.4 of 6 knowledge questions, which significantly improved to 5.4 at follow-up (P<.0001). The greatest increase in the percent responding correctly was regarding HPV and oropharyngeal cancer from 22% baseline to 91% at initial follow-up (P<.0001). Regarding Stage of Change, 14 (23%) of those not initially in the Action group had improved at least 1 stage. At the 6-month follow-up, 3 (43%) guardians reported completing the HPV vaccine series.
Conclusions: These results demonstrate limited knowledge about HPV and highlight the pediatric dental provider’s ability to educate. Since the greatest knowledge gap pertained to HPV and oropharyngeal cancer, it is important for pediatric dental providers to increase their role in HPV education. As oral cancers are the purview of dentists, practitioners should be involved with their patients’ consideration of the HPV vaccine.
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Evans, David Robert. "Survivorship experiences of working-age adults previously treated for oropharyngeal cancer : moving towards a post-treatment self, its hidden impact and an absence of recognition : an interpretative phenomenological analysis." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/112772/.
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Incidence of oropharyngeal cancer continues to increase in many countries worldwide, largely due to human papilloma virus (HPV) 16 & 18. Treatment for oropharyngeal cancer can result in long-term side effects. There may be enduring societal costs associated with the long-term physical and psychological side effects of treatment. Current literature suggests HPV may negatively affect a person’s lived post-treatment experience. However, there is little evidence to support this. Aim The aim was to explore the participants’ lived experience of survivorship following treatment for oropharyngeal cancer. From this, recommendations are made to inform future research. Method Twelve participants were recruited through two oncology centres in England. Participants were of working age and had completed active treatment between six months and five years prior to interview. A single interview was conducted with each participant. Interpretative phenomenological analysis (IPA) was used to inform the design and analysis. Consistent with IPA, the participants' individual experiences were analysed descriptively, conceptually and linguistically. Results All participants spoke about the physical side effects of treatment. Several described difficulties in coming to terms with a post-treatment self. These difficulties were exacerbated by the lack of visible outward change, thereby causing others to disregard the significance of their experience. There was a desire from some for external recognition of their experience. In attempting to establish a post-treatment self, those previously treated for oropharyngeal cancer may attempt to seek recognition for their experience. Gaining recognition can often be hampered due to the hidden nature of the experience to the outside world. Recommendations Several areas are suggested for future research. These include experiential research involving oropharyngeal cancer patients and their relatives, and people’s experiences of choice and informed consent. Auditing existing provision of supportive care post-treatment and exploring adaptation and recognition in a larger patient sample would also be beneficial for our understanding of this group.
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Azevedo, Paulo Roberto Medeiros de. "C?ncer de boca e orofaringe: tend?ncias e an?lise de sobrevida em Natal (RN)." Universidade Federal do Rio Grande do Norte, 2010. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13182.
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Previous issue date: 2010-05-07Introduction: Mouth cancer is classified as having one of the ten highest cancer incidences in the world. In Brazil, the incidence and mortality rates of oral cancer are among the highest in the world. Intraoral cancer (tongue, gum, floor of the mouth, and other non-specified parts of the mouth), the accumulated survival rate after five years is less than 50%. Objectives: Estimate the accumulated survival probability after five years and adjust the Cox regression model for mouth and oropharyngeal cancers, according to age range, sex, morphology, and location, for the city of Natal. Describe the mortality and incidence coefficients of oral and oropharyngeal cancer and their tendencies in the city of Natal, between 1980 and 2001 and between 1997 and 2001, respectively. Methods: Survival data of patients registered between 1997 and 2001 was obtained from the Population-based Cancer Record of Natal. Differences between the survival curves were tested using the log-rank test. The Cox proportional risk model was used to estimate risk ratios. The simple linear regression model was used for tendency analyses of the mortality and incidence coefficients. Results: The probability after five years was 22.9%. The patients with undifferentiated malignant neoplasia were 4.7 times more at risk of dying than those with epidermoid carcinoma, whereas the patients with oropharyngeal cancer had 2.0 times more at risk of dying than those with mouth cancer. The mouth cancer mortality and incidence coefficients for Natal were 4.3 and 2.9 per 100 000 inhabitants, respectively. The oropharyngeal cancer mortality and incidence coefficients were, respectively, 1.1 and 0.7 per 100 000 87 inhabitants. Conclusions: A low survival rate after five years was identified. Patients with oropharyngeal cancer had a greater risk of dying, independent of the factors considered in this study. Also independent of other factors, undifferentiated malignant neoplasia posed a greater risk of death. The magnitudes of the incidence coefficients found are not considered elevated, whereas the magnitudes of the mortality coefficients are high
Introdu??o: O c?ncer de boca ? classificado como uma das dez maiores incid?ncias de c?ncer no mundo. No Brasil, as taxas de incid?ncia e de mortalidade por esse c?ncer encontram-se entre as mais elevadas do mundo. Para o c?ncer intraoral (l?ngua, gengiva, base da boca e outras e n?o especificadas partes da boca), a taxa acumulada de sobrevida ap?s 5 anos ? menor que 50%. Objetivo: Estimar a probabilidade acumulada de sobrevida ap?s 5 anos, ajustar o modelo de regress?o de Cox para os c?nceres de boca e de orofaringe, segundo faixa et?ria, sexo, morfologia e localiza??o, para a cidade de Natal, Brasil. Descrever os coeficientes de mortalidade e de incid?ncia dos c?nceres de boca e de orofaringe e as tend?ncias desses coeficientes para a cidade de Natal, nos per?odos de 1980 a 2001 e de 1997 a 2001, respectivamente. Metodologia: Foi obtida a sobrevida de pacientes registrados entre 1997 e 2001 no Registro de C?ncer de Base populacional de Natal. Foram testadas as diferen?as entre as curvas de sobrevida atrav?s do teste log-rank. O modelo de riscos proporcionais de Cox foi utilizado para estimativas das raz?es de riscos. O modelo de regress?o linear simples foi utilizado para as an?lises de tend?ncia dos coeficientes de incid?ncia e de mortalidade. Resultados: A probabilidade acumulada ap?s 5 anos para todos os casos foi de 22,9%. Os pacientes com neoplasia maligna indiferenciada t?m 4,7 vezes mais risco de morrer do que aqueles com carcinoma epiderm?ide, enquanto que os pacientes com c?ncer de orofaringe t?m 2,0 vezes mais risco de morrer do que aqueles com c?ncer de boca. Os coeficientes padronizados de mortalidade e de incid?ncia do c?ncer de boca em Natal foram, respectivamente, 2,9 e 4,3 por 100 mil habitantes. Para o c?ncer de orofaringe 10 os coeficientes obtidos de mortalidade e de incid?ncia foram, respectivamente, 1,1 e 0,7 por 100 mil habitantes. Conclus?o: Identifica-se uma baixa taxa de sobrevida ap?s 5 anos. Pacientes com c?ncer de boca apresentam menos risco de morte, independentemente dos fatores considerados neste estudo. Tamb?m de forma independente dos demais fatores, a neoplasia maligna indiferenciada apresenta um maior risco de morte. As magnitudes dos coeficientes de incid?ncia encontradas n?o s?o consideradas elevadas, enquanto que de forma contr?ria est?o as magnitudes dos coeficientes de mortalidade
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Hanns, Elodie. "Analyse et caractérisation moléculaire de l'hypoxie intratumorale de carcinomes épidermoïdes de l'oropharynx." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ063/document.
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Les carcinomes épidermoïdes des voies aéro-digestives supérieures (VADS) se situent au sixième rang des cancers les plus fréquents dans le monde. Ces tumeurs sont liés à deux facteurs de risque : l’intoxication éthylo-tabagique (80% des cas) et l’infection de l’épithélium des VADS par les papillomavirus humain (HPV) à haut risque oncogène (20% des cas). Ces derniers définissent une sous-population de patients de meilleur pronostic. Une des hypothèses actuellement étudiées, afin d’expliquer la survie améliorée des patients HPV positifs, serait une hypoxie moindre dans ces tumeurs. En effet, les tumeurs des VADS sont fréquemment hypoxiques, et l’hypoxie intratumorale est un facteur de mauvais pronostic. Dans une première partie de cette thèse, nous avons entrepris une caractérisation moléculaire de l’hypoxie intratumorale dans les tumeurs humaines oropharyngées en fonction du statut HPV. Il apparaît que les tumeurs HPV positives présentent un statut hypoxique moindre comparées aux tumeurs HPV négatives. Ces tumeurs se caractérisent également par une abondante vascularisation intratumorale, qui pourrait être à l’origine de ce statut hypoxique moindre. Dans une deuxième partie, nous avons étudié l’adaptation à l’hypoxie de la lignée cellulaire HPV négative SQ20B et la lignée cellulaire HPV positive SCC90. De plus, des modèles de xénogreffes ont été établis à partir de ces mêmes lignées cellulaires et ont été analysés du point de vue de l’hypoxie intratumorale. De façon comparable aux tumeurs HPV positives, les xénogreffes obtenus à partir de la lignée SCC90 montre un statut hypoxique réduit comparés aux xénogreffes SQ20B. Les deux lignées cellulaires s’adaptent également différemment en hypoxie in vitro. La réponse à l’hypoxie dans la lignée SCC90 semble plus dynamique. En effet, la lignée SCC90 tente de s’adapter et de répondre à cet environnement hypoxique en induisant de fort niveau d’expression de gènes comparée à la lignée SQ20BHead and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignancy worldwide. The major risk factors for HNSCC identified are tobacco use and alcohol consumption (80% of all HNSCC), which seem to have a synergistic effect. A subgroup of HNSCCs (20% of cases), particularly those of the oropharynx, is caused by infection with high-risk types of human papillomavirus (HPV). Human papillomavirus HPV-related oropharyngeal squamous cell carcinoma defines a distinct clinical subgroup of head and neck cancer patients with improved prognosis. Currently, one of the several hypothesis studied to account for their improved survival outcomes could be a distinct hypoxia status compared to their HPV-negative counterpart. Indeed, tumour hypoxia is common in solid tumours including head and neck tumours, and hypoxia is a well-known poor prognosis factor. In first part of this thesis, we have performed a molecular characterisation of tumor hypoxia on cohort of oropharyngeal tumours according to HPV status of the patients. The results support the hypothesis that HPV-related tumours display a lesser hypoxia status compared to HPV-negative oropharyngeal tumours. These HPV-related tumours also characterize by an abundant tumour vascularisation, which could be responsible for a lesser hypoxia status. In a second part, we have studied the ability of the adaptation to hypoxia of the HPV-positive SCC90 cell line and HPV-negative SQ20B cell line. Furthermore, HPV-positive and HPV-negative HNSCC xenograft models have been established and have been analysed about tumor hypoxia. Similar to HPV-related HNSCC, tumours-derived HPV positive cell lines display a reduced hypoxic status compared to tumours-derived HPV negative cell lines. The two cell lines adapt also differently to in vitro hypoxia. In the HPV-positive cell line, the hypoxia response pathways could be more dynamics. Indeed, SCC90 cell lines attempt to adapt and to reply to hypoxic environment inducing highly expression of all of the hypoxia related genes compared to SQ20B cell lines
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Nishimura, Luciana Sigueta. "Polimorfismo PRO198LEU no gene para a enzima antioxidante dependente de selênio glutationa peroxidase 1 e risco de câncer epidermóide da cavidade oral e orofaringe." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/89/89131/tde-31012011-102550/.
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O selênio é um micronutriente essencial que apresenta ação antioxidante por meio de selenoproteínas, como a glutationa peroxidase 1 (GPX1). O polimorfismo PRO198LEU no gene em questão tem sido relacionado ao aumento do risco para alguns tipos de câncer, como o de mama e pulmão. Atualmente, o câncer de cabeça e pescoço é um importante problema de saúde pública no mundo e, inclusive, no Brasil. O objetivo do presente estudo foi avaliar eventual associação entre o polimorfismo GPX1 PRO198LEU e risco de câncer epidermóide da cavidade oral e orofaringe, bem como possível interação com utilização de tabaco e ingestão de álcool. O genótipo para o polimorfismo GPX1 PRO198LEU foi determinado pela técnica de PCR-RFLP (Reação em cadeia da polimerase - Polimorfismo no comprimento do fragmento de restrição) e seqüenciamento do DNA em 175 pacientes com câncer epidermóide da cavidade oral e orofaringe (grupo caso) integrantes de parte da casuística do Projeto Genoma Clínico do Câncer de Cabeça e Pescoço, e em 203 indivíduos sem a doença, internados nas enfermarias do Hospital Heliópolis (grupo controle). A freqüência do alelo de referência e do polimórfico foi de 0,72 e 0,28, respectivamente, em ambos os grupos. A freqüência dos genótipos encontrou-se em equilíbrio de Hardy-Weinberg nos grupos caso e controle. Não houve diferença estatisticamente significante (p>0,05) quanto à distribuição do genótipo para o polimorfismo GPX1PRO198LEU entre casos (50% PRO/PRO; 43% PRO/LEU e 7% LEU/LEU) e controles (51% PRO/PRO; 43% PRO/LEU e 6% LEU/LEU), não se verificando associação entre esse polimorfismo e risco para o câncer epidermóide da cavidade oral e orofaringe (Odds ratio = 1,02; 95% IC = 0,68-1,53; p = 0,51; homozigotos polimórficos e heterozigotos agrupados comparados a homozigotos de referência). Além disso, a utilização de tabaco ou ingestão de álcool não modificou a ausência de associação entre o polimorfismo GPX1 PRO198LEU e o câncer em questão (Utilização de tabaco maior que 20 pack years: Odds ratio = 0,94; 95% IC = 0,53-1,70; p = 0,49; Ingestão de álcool maior que 80g de etanol/dia: Odds ratio = 0,80; IC = 0,46-1,39; p = 0,26). Conclui-se que esse polimorfismo não aumenta o risco para o câncer epidermóide da cavidade oral e orofaringe.Selenium is an essential micronutrient that presents antioxidant activity through selenoproteins such as glutathione peroxidase 1 (GPX1). PRO198LEU polymorphism in this gene has been associated with increased risk for some cancer types such as breast and lung cancers. Currently head and neck cancer is a major public health problem in the world and in Brazil. The aim of this study was to evaluate a possible association between GPX1 PRO198LEU polymorphism and risk of oral cavity and oropharyngeal squamous cell cancer. GPX1 PRO198LEU polymorphism genotype was determined by PCR-RFLP method (Polymerase chain reaction-Restriction fragment length polymorphism) and DNA sequencing in 175 patients with oral cavity and oropharyngeal squamous cell cancer (case group) from the Head and Neck Cancer Clinical Genome Project, and in 203 cancer-free individuals, hospitalized in the wards of Heliopolis Hospital (control group). The frequency of reference and polymorphic allele was 0.72 and 0.28, respectively, in both groups. The genotype distribution was in Hardy-Weinberg equilibrium in case and control groups. There was no statistically significant difference (p> 0.05) on the distribution of genotype for the GPX1 PRO198LEU polymorphism between cases (50% PRO/PRO, 43% PRO/LEU and 7% LEU/ LEU) and controls (51% PRO/PRO, 43% PRO/LEU and 6% LEU/LEU) and there was no association between this polymorphism and risk for oral cavity and oropharyngeal squamous cell cancer (odds ratio = 1.02, 95% CI = 0.68 to 1,53; p = 0.51; polymorphic homozygotes and heterozygotes combined compared with reference homozygotes). Furthermore, the use of tobacco or alcohol intake did not change the lack of association between the GPX1 PRO198LEU polymorphism and cancer risk (use of tobacco greater than 20 pack years: odds ratio = 0.94, 95% CI = 0.53 to 1,70, p = 0.49; alcohol intake greater than 80g etanol/day: Odds ratio = 0.80, CI = 0.46 to 1.39, p = 0.26). We conclude that this polymorphism does not increase the risk of oral cavity and oropharyngeal squamous cell cancer.
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Santos, Edilmar de Moura. "Valor progn?stico de c?lulas TCD8+ E natural killer em carcinoma epiderm?ide oral e orofaringeano tratado com radioterapia e quimioterapia." Universidade Federal do Rio Grande do Norte, 2012. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17124.
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Previous issue date: 2012-02-09Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
The most common malignant neoplasm of the oral cavity and oropharynx are squamous cell carcinoma. Injuries to the same stage and subjected to the same treatment protocol have sometimes different evolutionary courses. The scope of this study was to investigate, through a retrospective cohort, associations between the number of CD8 + T cells and natural killer, identified immunohistochemically in the inflammatory infiltrate in a series of cases of oral squamous cell carcinoma and orofaringeano, and the level of tumor response to radiotherapy and chemotherapy, overall survival and relapse-free survival of patients. We identified 54 patients with unresectable disease were treated exclusively with radiotherapy and chemotherapy. The median follow-up was 22 months. The sample was characterized by the predominance of male subjects, median age 60 years, all were smokers. The most frequent site was the tongue and 81.5% were in stage IV. Patients with disease in the oral cavity had a worse response to treatment (p = 0.006), worse relapse-free survival (p = 0.007), worse overall survival (p = 0.007). The advanced T stage was shown a negative prognostic factor (p= 0.006) for the clinical treatment response made. Immunohistochemistry was performed to select CD8 + cells (anti-CD8) and NK cells (anti-CD57). Lymphocytes positive and negative markings were counted using the program ImageJ ?. Two groups were created for each marking evaluated: Group I patients with more than 50% cells positive, Group II: less than 50% of labeled cells. For CD8 + cells detected in 38 (70.3%) of Group I were CD8 + and 16 (29.7%) Group II CD8 +. For NK cells, 26 (48.15%) Group I NK and 28 (51.85%) Group II NK. Regarding the clinical response to treatment, we observed that 39% of patients achieved a complete response and 25.9% remained without recurrence at the end of follow-up. These results were better in Group I CD8 + (p = 0.2). Identified that 72.2% of patients progressed to death, this finding had no association with the immunohistochemical data. There was no statistically significant differences between the number of CD8 + and NK cells and the ability of tumor response to radiotherapy and chemotherapy, or with overall survival and relapse-free survival of patients. However, especially in relation to a learned response, we found that this group of patients with advanced disease have a low count of CD8 + T cells active. Believing in the role that the immune response plays in the local fight against neoplastic cells, however, our results do not support the use of quantitative analysis of CD8 + T cells and NK cells as a prognostic factors for oral squamous cell carcinoma and oropharynx
A neoplasia maligna mais frequente da cavidade oral e da orofaringe ? o carcinoma epiderm?ide. Les?es com o mesmo estadiamento e submetidas ao mesmo protocolo terap?utico apresentam, por vezes, cursos evolutivos diferentes. O escopo do presente trabalho foi investigar, atrav?s de um coorte retrospectivo, associa??es entre a quantidade de c?lulas TCD8+ e natural killer, identificadas imuno-histoquimicamente no infiltrado inflamat?rio de uma s?rie de casos de carcinoma epiderm?ide oral e orofaringeano, e o n?vel de resposta tumoral ao tratamento radioter?pico e quimioter?pico, a sobrevida global e sobrevida livre de recidiva dos pacientes. Foram identificados 54 pacientes com doen?a irressec?vel, tratados exclusivamente com radioterapia e quimioterapia. A mediana de seguimento foi de 22 meses. A amostra se caracterizou pelo predom?nio de indiv?duos masculinos, com idade mediana de 60 anos; todos eram tabagistas. O s?tio mais frequente foi a l?ngua oral e 81,5% encontravam-se no est?dio IV. Os pacientes com doen?a na cavidade oral tiveram uma pior resposta ao tratamento (p=0,006), pior sobrevida livre de recidiva (p=0,007), pior sobrevida global (p=0,007). O est?dio T avan?ado se demonstrou um fator progn?stico negativo (p=0,006) para a resposta ao tratamento cl?nico efetuado. Foi realizada imuno-histoqu?mica para marcar c?lulas CD8+ (anti-CD8) e c?lulas NK (anti-CD57). Os linf?citos positivos e negativos para as marca??es foram contados atrav?s do programa ImageJ?. Dois grupos foram criados para cada marca??o avaliada: Grupo I: pacientes com mais de 50% das c?lulas positivas; Grupo II: menos de 50% das c?lulas marcadas. Para as c?lulas CD8+ detectamos que 38 (70,3%) eram do Grupo I CD8+ e 16 (29,7%) do Grupo II CD8+. Para as c?lulas NK, 26 (48,15%) Grupo I NK e 28 (51,85%) Grupo II NK. Em rela??o ? resposta cl?nica ao tratamento, observamos que 39% dos pacientes obtiveram resposta completa e 25,9% permaneceram sem recidiva ao final do seguimento. Esses resultados foram melhores no Grupo I CD8+ (p=0,2). Identificamos que 72,2% dos pacientes evolu?ram para o ?bito, esse achado n?o teve associa??o com os dados imuno-histoqu?micos. N?o se observou diferen?as estatisticamente significantes entre a quantidade de c?lulas CD8+ e NK e a capacidade de resposta tumoral ao tratamento radioter?pico e quimioter?pico, nem com a sobrevida global e sobrevida livre de recidiva dos pacientes. Contudo, principalmente em rela??o a resposta adquirida, detectamos que este grupo de pacientes com doen?a avan?ada tem uma baixa contagem de c?lulas TCD8+ ativas. Acreditando no papel fundamental que a resposta imune exerce no combate local ?s c?lulas neopl?sicas; no entanto, nossos resultados n?o suportam a utiliza??o da an?lise quantitativa das c?lulas TCD8+ e NK como um dos fatores progn?sticos para o carcinoma epiderm?ide oral e de orofaringe
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Ramdas, Yastira. "Pattern of practice of radical radiation therapy for oropharyngeal cancers: a retrospective review from January 2009 to December 2012." Thesis, 2015. http://hdl.handle.net/10539/18478.
Full textAbstract:
A research report submitted to the Faculty of Health Sciences, University of the
Witwatersrand, Johannesburg, in partial fulfilment of the requirement for the degree of
Masters of Medicine in the branch of Radiation Oncology
Johannesburg 2015Radiation therapy is a highly effective method of treating oropharyngeal carcinoma, either as a single modality treatment with concurrent chemotherapy or as an adjuvant treatment after surgical resection. There exists an association with human papillomavirus (HPV) and oropharyngeal cancer, dividing oropharyngeal carcinoma into HPV positive oropharyngeal carcinoma and HPV negative oropharyngeal carcinoma. Overall survival has been analysed in these two groups and have been shown to be 80-95% for HPV positive oropharyngeal carcinomas and 57-62% in HPV negative subgroup at 3 years respectively. This retrospective review was intended to analyse patient response to treatment, overall survival, local disease free survival and the difference between HPV positive oropharyngeal carcinoma and HPV negative oropharyngeal carcinoma at Charlotte Maxeke Johannesburg Academic Hospital: Department of Radiation Oncology. Patients and methods A retrospective descriptive study was conducted on patients having received radical radiation therapy, with or without chemotherapy, from January 2009 to December 2012 with a histologically confirmed diagnosis of squamous cell carcinoma involving oropharyngeal sites only. The information obtained from records of forty-eight patients was captured on the prescribed data sheets designed for this study. Results Forty-eight eligible patients were accrued within this retrospective study. The median age of the patient group was 56 years (range 32-78) and comprised of 10 females and 38 males. The performance status was mainly Eastern Cooperative Oncology Group (ECOG) 1 (83%). The radiation therapy dose was within the range 60-70Gy, with majority patients completing 70 Gy (65%). Concurrent chemoradiation was given in 59% of patient group (28 patients). The most common site being the base of tongue (60%), followed by tonsil (36%), soft palate (2%) and posterior pharyngeal wall (2%). Eighty five percent of patients were stage IV oropharyngeal carcinoma. Only 6% of patients were tested for HPV-DNA PCR, and all were HPV positive. A total of 79% patients had a positive smoking history and 50% consumed alcohol regularly. Fifty six percent of patients tested negative for HIV, 14.6% tested positive for HIV and 29.3% had unknown HIV status. At the time of the analyses (March 2014) only 7 (15%) of patients were alive. The 2 year overall survival was 13%, the local disease free survival at 2 years was 59%. None of the prognostic factors were predictive of overall survival using univariate and multivariate analysis. Conclusion Majority of patients present in stage IV lesions with commonest sites of involvement being Base of Tongue. The local disease free survival of 2 years was 59% and the overall survival of 15%. There was no impact of prognostic factors studied on overall survival.
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Knapik, Monika. "Modèle cellulaire de carcinogenèse pour les cancers de l’oropharynx induits par le VPH." Thèse, 2014. http://hdl.handle.net/1866/13405.
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Problématique: Le virus du papillome humain (VPH) est présent dans près de 50% des cancers de l’oropharynx. Le potentiel oncogénique du VPH est encodé dans les oncoprotéines E6 et E7, qui agissent en modulant différents gènes, dont les gènes suppresseurs de tumeur p53 et pRb. Les cellules VPH positives démontrent une altération au niveau de la signalisation de la réponse aux dommages à l’ADN (RDA), un mécanisme de contrôle dans l’arrêt de la croissance des cellules ayant subit des dommages au niveau de leur ADN.
Hypothèse et objectifs : Nous croyons que les défauts au niveau de la RDA des cancers VPH positifs peuvent être exploités afin de sensibiliser préférentiellement les cellules cancéreuses aux traitements de radiothérapie. Cette stratégie de recherche nécessite l’élaboration d’un modèle cellulaire de carcinogenèse isogénique pour le cancer de l’oropharynx que nous proposons de développer et de caractériser. L’étude vise à dériver des lignées isogéniques à partir de kératinocytes primaires et cellules épithéliales de l’oropharynx pour ensuite valider la carcinogenèse de notre modèle in vitro & in vivo
Méthodologie : Des lignées cellulaires de kératinocytes primaires et de cellules épithéliales de l’oropharynx ont été successivement modifiées par transduction afin de présenter les mutations associées aux cancers de l’oropharynx induits par le VPH. Les cellules ont été modifiées avec des lentivirus codants pour la télomérase (hTERT), les oncogènes E6, E7 et RasV12. Afin de valider la cancérogenèse in vitro de notre modèle, des études d’invasion en matrigel et de croissance sans ancrage en agar mou ont été réalisées. Les populations cellulaires transformées ont été ensuite introduites dans des souris immunodéficientes afin d’évaluer leur tumorogénicité in vivo.
Résultats : À partir des plasmides recombinés construits par méthodes de clonage traditionnelle et de recombinaison « Gateway », nous avons produit des lentivirus codants pour la télomérase humaine (hTERT), les oncogènes viraux E6 et E7 et l’oncogène Ras. Les kératinocytes primaires et cellules épithéliales de l’oropharynx ont été infectés successivement par transduction et sélectionnés. Nous avons validé l’expression de nos transgènes par méthode d’immunofluorescence, de Western Blot et de réaction de polymérisation en chaîne quantitative en temps réel (qRT-PCR). Nous avons établi trois lignées des cellules épithéliales de l’oropharynx (HNOE) à partir d’échantillons tissulaires prélevés lors d’amygdalectomie (HNOE42, HNO45, HNOE46). Les cellules transduites avec le lentivirus exprimant le promoteur fort CMV/TO de l’oncogène RasV12 ont présenté un changement morphologique compatible avec une sénescence prématurée induite par l’oncogène Ras. En exprimant des quantités plus faibles du RasV12 mutant, la lignée cellulaire HEKn hTERT-E6-E7 PGK RasV12 a réussi à échapper à la sénescence induite par l’oncogène Ras. La population cellulaire exprimant HEKn hTERT-E6-E7-PGK RasV12 a présenté un phénotype malin en culture et à l’étude d'invasion, mais n’a pas démontré de résultats positifs à l’étude de croissance sans ancrage en agar mou ni en xénogreffe en souris immunodéficientes.
Conclusion : Nos résultats démontrent qu’en présence des oncogènes viraux E6 et E7, il y a un troisième mécanisme suppresseur de tumeur qui médie la sénescence induite par l’oncogène Ras. Nous avons identifié que la présence de E6 seule ne suffit pas à immortaliser les kératinocytes primaires humains (HEKn). Nous n’avons pas réussi à créer un modèle in vitro de carcinogenèse pour les cancers de l’oropharynx induits par le VPH.Background: Human papillomavirus (HPV) is present in almost 50% of all oropharyngeal cancers. The oncogenic potential of HPV is encoded by the E6 and E7 oncoproteins, which act by modulating different genes, including tumour suppressor genes p53 and pRb. The process of inactivation of p53 and pRb is largely responsible for the genomic instability that contributes to malignant transformation of cells. HPV-positive cancer cells show an alteration in their DNA Damage Response (DDR) signalling pathway that allows them to inhibit key tumour suppressor genes and to ignore DNA damage signals. Hypothesis and objectives: We believe that these DDR defects can be exploited to preferentially sensitize cancerous cells to radiotherapy by using a defined cell culture model. We propose to characterize a defined cell culture model for HPV induced oropharyngeal cancer. Derive isogenic cell culture lines from primary skin keratinocytes and oropharyngeal epithelial cells. and to validate the carcinogenesis of our model in vitro and in vivo. Methods: We propose to use primary skin keratinocytes and oropharyngeal epithelial cells which will be sequentially modified by transduction using a Gateway Lentiviral System to present the mutations associated with HPV induced oropharyngeal cancer. The cells will be modified with lentivirus encoding the human telomerase (hTERT), E6, E7 and Ras oncogenes. To validate the in vitro carcinogenesis of our model, we will assess anchorage independent growth and invasiveness by means of soft agar medium and matrigel studies. To assess in vivo tumorigenicity, the transformed cell populations will be introduced into immunodeficient mice. Results: We constructed recombinant lentivector plasmids using traditional cloning and Gateway recombination methods. Using the constructed lentivectors, we generated lentiviruses encoding the catalytic subunit for human telomerase (hTERT), the E6 and E7 viral oncogenes and Ras oncogene. Primary keratinocytes and oropharyngeal epithelial cells were infected successively by transduction with the above-mentioned lentiviruses and then underwent selection. We validated the expression of our transgenes by methods of immunofluorescence, Western blot and real-time quantitative polymerase chain reaction (qRT-PCR). We have successfully established and kept in culture three lines of epithelial oropharyngeal cells (HNOE42, HNOE45, HNOE46) from tissue samples collected during tonsillectomy. Cells transduced with lentivirus expressing CMV/TO, a strong promoter for the RasV12 oncogene, showed morphological changes compatible with premature Ras oncogene induced senescence. Cell line HEKn hTERT-E6-E7 PGK RasV12 managed to escape Ras oncogene induced senescence by expressing lower amount of mutated RasV12. The HEKn hTERT-E6-E7-PGK RasV12 cell line presented a malignant phenotype in culture and on matrigel invasion assay. However, soft agar assay for anchorage independent cell growth and xenograft assay in immunodeficient mice were both negative for tumorigenicity. Conclusion: Our results demonstrate that in the presence of E6 and E7, a third tumor suppressor mechanism mediates Ras oncogene induced senescence. Furthermore, we have found that the presence of E6 alone is not sufficient to immortalize primary human keratinocytes (HEKn). We have not managed to create an in vitro carcinogenesis cell culture model for HPV induced oropharyngeal cancer.
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Pei-shan, Ho, and 何佩珊. "The epidemiology of oropharyngeal cancer." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/x4r333.
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博士高雄醫學大學
牙醫學研究所
90
The Incidence of Oropharyngeal Cancer in Taiwan Abstract Backgroud: Orapharyngeal cancer is the one of the most common cancers in the world. The purpose of this study was to examine the time trends of oropharyngeal cancer from 1979 to 1996 in Taiwan. Method: Traditional cohort analysis was employed to show the birth-cohort effect of oropharyngeal cancer incidence. Age-period-cohort model analysis was used to examine the age, period, and cohort effect betw Ethnic Differences in Oropharyngeal Cancer of Taiwan Abstract Background: Oropharyngeal cancer incidence of Taiwan is remarkable high in the world. But ethnic difference may exist in pattern of oropharyngeal cancer of Tawain. The purpose of this study was to examine the oropharyngeal cancer pattern among different ethnic groups of Taiwan. Methods: The population divided into three ethnic groups, which were Fukkien, Hakka, and aboriginal communities. Standardized mortality rate ratios (SMRs), standardized incidence rate ratios (SIRs) and their ratios were estimated among these ethnic groups from 1971-1997. Results: We found that the oropharyngeal cancer in high betel quid chewing aboriginal group was significantly higher than reference group (male: SMR=1.21, SIR=1.12; female SMR=4.3, SIR=2.62). The aboriginal groups also had an excess oropharyngeal cancer (based on SMR/SIR ratios), especially in aboriginal females. The incidence and mortality rate of oropharyngeal cancer in Hakka was significantly lower than in reference group. Conclusion: The pattern of oropharyngeal cancer in Taiwan showed ethnic differences. Betel quid chewing might be the major etiology related with the higher oropharyngeal cancer of aboriginal groups, and the excess fatality in aboriginal groups might due to lower socioeconomic status and worse medical access, especially in females. een intra-oral and pharyngeal cancer. Result: A significant rising trend in oropharyngeal cancer has been seen in males. From the proportion of subsites, the major increasing subsites were on the tongue and mouth in males, and on the tongue in females. In males, we also found an increasing trend in successive cohorts born after 1929. The incidence of intra-oral cancer of male had a greater increase than pharyngeal cancer in the younger age group, recent time periods, and the late birth cohorts. Conclusion: The increasing trend of oropharyngeal cancer incidence of Taiwan is likely to be heavily influenced by the rising consumption of alcohol and betel quid, and the effect of these etiologies was more significant on intra-oral cancer in recent periods, later cohorts, and the younger age group.
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Yang, Hsiu-Fei, and 楊琇妃. "Epidemiological study of oropharyngeal cancer－ Distinct features in Changhua." Thesis, 2006. http://ndltd.ncl.edu.tw/handle/63458103288788221560.
Full textAbstract:
碩士國立彰化師範大學
數學系所
94
Abstract Purpose: Oropharyngeal cancer is one of the fastest increasing malignancies in Taiwan. Among the counties on the island, Changhua has been ranked in the top three in the list of oropharyngeal cancer incidence. We start the study to better characterize the epidemiology of oropharyngeal cancer in the Changhua County. The study goal was to (1) Compare the incidence rate of Changhua to rest areas in Taiwan and the correlation of risk factors. (2) Compare the survival rate of Changhua to rest areas in Taiwan by gender. Methods: We use the complete registered records of oral cancer from the data bank of Department of Health (DOH). The records of 30041 oropharyngeal cancer patients(ICD9 140-149, except 142、147) from 1986 to 2001. We study the trend of incidence rate, age of distribution, anatomic sites, survival rate of oropharyngeal cancer in Changhua and compare different with rest areas in Taiwan. In addition, we correlate the incidence rate with known risk factors (betel quid chewing, smoking, and alcohol drinking) by regression method. We selected some environmental risk factor such as water pollution, metal pollution in farmland and industrial region, to further study the relationship in Changhua County. Results: Incidence rate of oropharyngeal cancer in Changhua is among the highest in the world, and was the highest among the 23 counties in Taiwan in 2001 (45.07 per 105 per year). We can see a steady increase in the male oropharyngeal cancer, the male to female incidence ratio of oropharyngeal cancer increased to 19:1 in 2001. The most common site was buccal, while it was tongue in the rest counties. Finally, Changhua is the only outlier in our regression model, indicating an unusual relation between cancer incidence and prevalence of betel quid chewing in Changhua. To investigate the influence of environmental factors, the results show that the contents of arsenic in groundwater and numbers of factory are on the high side in high incidence area, the correlation between high incidence rate in tongue and the contents of arsenic and nickel in farmland, high incidence rate in tongue and numbers of factory in town are positive. The correlation between high incidence rate in buccal mucosa and numbers of factory in town is also positive. Using Kaplan-Meier survival analysis, the male of oropharyngeal cancer five-year survival rate was 51.11% in Changhua, similar to looks of rest areas in Taiwan (52.23% ). In contrast, the female five-year survival rate was 61.03% in Changhua, low nearly 8% with rest areas in Taiwan(69.10%), the adjusted hazard ratio of Changhua versus rest areas in Taiwan was 1.18 (95%CI, 0.68-2.05) for oropharyngeal cancer death. Conclusions: Over the years of the study, the incidence of male oropharyngeal cancer increased significantly from 6.31 to 27.04 per 105 men per year. Age of diagnosis of male oropharyngeal cancer is shifting to a younger age in recent years. The mean age of 54 in 1986-1989 is decreasing to 51 in 1998-2001 The high and fast increasing incidence of oral cancer in Changhua signifies the importance of this cancer locally, no less than that of liver cancer and lung cancer. An unusual relation with known risk factors (betel quid chewing, smoking, and alcohol drinking) indicates other unknown factor/factors may be involved in the etiology of oral cancer in Changhua. We tried to separate Changhua county by incidence rate in each town and village and probable environment factors. Although we still can’t find the strong evidence out by searched environment data presently, but we also find out the specialty of oropharyngeal cancer in Changhua by multi discussion. Further study is needed, and is ongoing by searching new data to clarify the specialty of oropharyngeal cancer in Changhua.
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Dahlstrom, Kristina Riis Sturgis Erich M. "The association of sexual behavior with oropharyngeal cancer and correlations with HPV-16 serologic status." 2007. http://proquest.umi.com/pqdweb?did=1292467891&sid=1&Fmt=2&clientId=68716&RQT=309&VName=PQD.
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Wu, Pei-Shan, and 吳佩珊. "A mathematical model of oropharyngeal airway space volume assessment by computed tomography in oral cancer patients." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/63658994258831034873.
Full textAbstract:
碩士國立陽明大學
臨床牙醫學研究所
96
The incidence and increase rate of oral cancer have kept increasing in Taiwan recently. After treatment of oral cancer, including surgery, radiotherapy and/or chemotherapy, the incidence causing airway change varied from 8%-92%, indicating that patients who have been successfully treated for oral cancer often have a partially airway changes after surgery. The methods analyzing airway space change in the literature include magnetic resonance imaging (MRI), lateral cephalometric film, and 3-dimensional computed tomography (3-D CT). The 3-D CT has been reported as a reliable instrument evaluating the volumetric change of airway space. The objective of the present investigation is to establish norm data on this line of study by a mathematical model of oropharyngeal airway space volume assessment based on a 3-D CT reconstruction. Results showed that the oropharyngeal airway space of patients with oral cancer after treatment was significantly larger than that before treatment. The factors explaining the current results are also discussed.
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Vashist, Aastha. "Genetic Differentiation of oral and oropharyngeal carcinoma based on Human Papillomavirus Status and Race." 2016. http://scholarworks.gsu.edu/iph_theses/500.
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INTRODUCTION: Head and neck cancer is one of the most common malignancy in the world. While it has been associated with several factors like alcohol consumption and smoking, there is approximately 25% of head and neck cancer that can be attributed to Human Papillomavirus (HPV) especially HPV 16. HPV associated cancer has been associated with a better prognosis as compared to HPV negative cancers. It has also been shown in previous studies that HPV-negative African Americans have a higher mortality rate as compared to HPV associated cancers in European Americans and HPV-negative European Americans patients. The three states of HPV associated cancers have been compared, which included HPV active, HPV inactive and HPV negative.
AIM: The study aims include: 1) Compare the differences in the gene expression profiles of HPV negative HNSCC in AA from EA patients, and determine the differences in their biological make up. 2) Explore and compare the genetic expression profiles of HPV-active, HPV-inactive and HPV-negative head and neck cancer patients.
METHODS: A secondary data analysis was conducted on 36 oropharyngeal cancer tissues samples with different HPV status (HPV-active, HPV-inactive and HPV- negative). ANOVA was conducted in R to compare all the three groups from each other and identify the genes that were differentially expressed. Bayes Moderated paired t-test was used to compare two groups of HPV-negative European Americans with HPV-negative African Americans.
RESULTS: Our analysis revealed that the genes that were differentially expressed in HPV- active and HPV-negative analysis were different from HPV-active and HPV-inactive analysis. Our analysis also identified genes that were differentially expressed in African Americans as compared to European Americans.
DISCUSSION: This study provides the genetic expression profiles in different groups (European Americans and African Americans) based on different HPV stages. Despite the small sample size of our data, we were able to identify the genes that were differentially expressed amongst different conditions in patients who had oropharyngeal carcinoma. We were also able to identify the genes involved in HPV-negative oral cancer comparing the African Americans to the European Americans.
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Valente, Carlos Emanuel Baptista. "Modelo de infeção do HPV na orofaringe: revisão narrativa." Master's thesis, 2021. http://hdl.handle.net/10284/10821.
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O Vírus do Papiloma Humano (HPV), vírus comummente associado ao carcinoma cervical, também infeta as células basais do epitélio estratificado da orofaringe e está associado, etiologicamente, ao Cancro de Células Escamosas da Cabeça e Pescoço. A infeção oral por HPV, nomeadamente pelo HPV-16 e 18, apresenta fatores de risco clássicos, como o tabaco e o álcool, assim como a sua incidência varia de acordo com o comportamento sexual dos indivíduos infetados.
A infeção por HPV na orofaringe apresenta um curso muito próprio, não só pelo local anatómico afetado, mas pelo facto de um número elevado de indivíduos com tumores HPV+ em estágio inicial serem assintomáticos.
O Carcinoma de Células Escamosas da Orofaringe, quando associado à infeção por HPV, tem melhor prognóstico, apesar do modelo de infeção ser pouco conhecido. É de elevada importância não só o seu estudo, como também a análise da prevenção que poderá ser realizada pelo médico dentista.The Human Papilloma Virus (HPV), a virus commonly associated to cervical carcinoma, also infects the basal cells of the stratified epithelium of the oropharynx and is etiologically associated to Squamous Cell Cancer of the Head and Neck. Oral infection by HPV, namely by HPV-16 and 18, presents classic risk factors such as tobacco and alcohol and its incidence vary according to the sexual behaviour of the infected individuals. HPV infection in the oropharynx has a very specific course not only because of the anatomical site affected, but also because a high number of individuals with early-stage HPV+ tumours are asymptomatic. Oropharyngeal Squamous Cell Carcinoma when associated with HPV infection has a better prognosis although the model of infection is not well known. It is very important not only to study it but also to analyze the prevention that may be carried out by the dentist.
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Elfring, Tracy Tamiko. "Surgical reconstruction of the lingual and hypoglossal nerves in oropharyngeal cancer: anterior oral cavity sensorimotor and quality of life outcomes." Master's thesis, 2010. http://hdl.handle.net/10048/1163.
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This study explores the effects of surgical reconstruction and nerve repair on sensorimotor function and quality of life (QOL) for patients with base of tongue (BOT) cancer compared to healthy, age-matched adults. Sensations were tested on the anterior two-thirds of the oral tongue for two-point discrimination, light touch, taste, temperature, form and texture on 30 patients with BOT reconstruction with radial forearm free-flap and on 30 controls. Results indicated sensation for the unaffected tongue side and affected side with lingual nerve intact was comparable to controls, with poorer sensory outcomes for nerve repair. However, lingual nerves repaired with reanastomosis provided superior results to cable-grafting and severed nerves. Patients had decreased motor function only when the hypoglossal and lingual nerves were affected. Patients' QOL responses on the UW-QOL and EORTC QLQ-H&N35 revealed involvement of lingual and hypoglossal nerves resulted in poorer QOL outcomes. QOL interviews revealed additional problematic issues in this population not identified by standardized questionnaires.Speech-Language Pathology
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Morey, Tristan. "Accuracy of Imaging Modalities for Detecting Extracapsular Spread of Cervical Lymph Node Metastases in HPV-Associated Oropharyngeal Cancer: A Systematic Review." Thesis, 2022. https://hdl.handle.net/2440/135910.
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Background: Extracapsular spread (ECS) of lymph node metastases is associated with poor prognosis and its detection in head and neck cancer (H&NC) is crucial for treatment planning. Commonly used imaging modalities to detect ECS in H&NC include computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasonography (US). Currently there is no gold standard imaging modality to detect ECS in H&NC, leaving clinicians to rely heavily on clinical examination and surgical histopathology for ECS based treatment decisions. The purpose of this study was to undertake a systematic review using Joanna Briggs Institute (JBI) methodology that aimed at identifying and synthesising the best available evidence regarding the accuracy of conventional imaging modalities and their abilities to detect ECS in the specific population group of patients with human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). Inclusion criteria: Type of participants: Participants were those with a confirmed diagnosis of HPV+ OPSCC and suspected diagnosis of cervical lymph node metastases and ECS. Participants were not excluded due to age, sex, race or education status. Type of index tests: This review examined studies that utilised a conventional imaging modality to detect radiologic ECS in HPV+ OPSCC. Type of reference test: This review examined studies that utilised surgical histopathology as the reference standard for the diagnosis of ECS (gold standard for ECS detection). Type of outcomes: This review examined two primary and four secondary outcomes of interest. The primary outcomes of interest included: sensitivity and specificity measures with 95% confidence intervals for each imaging modality used to detect ECS in HPV+ OPSCC. The secondary outcomes included: positive predictive value (PPV), negative predictive value (NPV), area under the ROC curve (AUC) and interobserver agreements (K) (where applicable) for the different imaging modalities. Diagnosis of interest: The phenomena of interest in this review was ECS of cervical lymph node metastases (also known as extra-nodal extension (ENE)). Type of studies: This review examined published studies that examined the diagnostic accuracy (including sensitivity and specificity) of an imaging modality used to detect ECS in HPV+ OPSCC. Diagnostic cohort studies were the preferred study design for inclusion. All six of the included studies were retrospective cohort studies. Methods: Methodological approach: The methodological approach to the review was based on JBI guidance for systematic reviews involving diagnostic test accuracy (DTA) studies. Search strategy: A comprehensive search using a three-phased approach was conducted across four databases, one clinical trials register, as well as a manual search for primary studies (published) in the reference lists of all included studies. There was no restriction on publication date, however. only studies in English were included in the review. Methodological quality: Two reviewers assessed the methodological quality of the included studies using the QUADAS-2 tool. The QUADAS-2 tool is structured around assessing for risk of bias in four domains; Patient Selection, Index Test, Reference Standard, and Flow and Timing. Data extraction: Quantitative data was extracted using the JBI data extraction tool for DTA studies. Data analysis Meta-analysis and assessment of heterogeneity was conducted on four CT studies using a random-effects model. The remaining two studies underwent a narrative synthesis. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to assess the certainty in the evidence. Results: Out of 1772 hits, six retrospective cohort studies were included in the review and four underwent meta-analysis. Four investigated the diagnostic ability of CT, one investigated PET/CT, and one investigated 'CT and MRI' (with no separation of index test to outcomes). Meta-analysis of the four CT studies showed CT had an overall sensitivity of 77% (60-94%) and specificity of 60% (47-73%). PET/CT had a sensitivity of 86% (73-94%) and specificity of 76% (61-87%). 'CT and MRI' had a sensitivity of 62% (53-70%) and specificity of 78% (70-84%). No meta-analysis or comparison meta-regression could be performed on the PET/CT or 'CT and MRI' studies. Conclusions: The findings of this review imply pooled CT specificity values (60%) are too low to suggest clinical value for CT as a diagnostic tool to detect ECS in HPV+ OPSCC. Pending further research, the use of CT and PET/CT however might have clinically acceptable sensitivity and negative predictive values to help confirm the absence of radiologic ECS in HPV+ OPSCC. No studies on MRI or US were identified for assessment of ECS in HPV+ OPSCC. Implications for practice: There is insufficient evidence to suggest CT or PET/CT are reliable diagnostic tools for radiological detection of ECS in HPV+ OPSCC. Further studies of high-quality involving CT, PET/CT, MRI and US are required to help establish clinical guidance and a gold standard for radiologic ECS detection in HPV+ OPSCC.Thesis (MClinSc) -- University of Adelaide, Joanna Briggs Institute, 2022
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Wu, Eric Longhua. "Translational assessment of primary tumor-derived cells." Thesis, 2014. https://hdl.handle.net/2144/14332.
Full textAbstract:
Only a few individual cells within less than 5% of all primary tumors form the cell lines commonly used in cancer research. These growth bottlenecks result in cell lines that are often poor models of primary tumors. Co-culture of primary tumor-derived cells with an irradiated mouse fibroblast feeder layer and ROCK inhibitor, known as the Georgetown Method, offers a way to culture over 80% of tumor-derived cells in vitro to create more representative tumor cell models. In our studies, we optimized the Georgetown Method to culture head and neck cancer cells, including oropharyngeal squamous cell carcinoma, and investigated its mechanism of conditionally immortalizing cells in culture. Differential trypsinization and regular feeder layer replacement were found to significantly improve the efficacy of immortalizing co-cultured cells at both atmospheric and physiological oxygen levels. Medium conditioned by irradiated fibroblasts can also substitute for direct co-culture with a feeder layer. The Georgetown Method was found to maintain low levels of p16 in co-cultured cells, suggesting a potential mechanism by which the Georgetown Method prevents differentiation and senescence. Our ability to culture over 80% of primary tumor-derived cells allows us to test the translational value of tumor-derived cell cultures and xenografts using BH3 profiling. Conditioned medium simplifies maintenance of cell cultures and will also allow us to perform high-throughput screens without the need to separate tumor-derived cells from the fibroblast feeder layer. The Georgetown Method provides opportunities to expand small tissue specimens for future diagnostics, therapeutics, and biobanking.