human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus ( HPV ) infection , but empirical evidence is lacking . PATIENTS AND METHODS HPV status was determined for all 271 oropharyngeal cancers ( 1984 - 2004 ) collected by the three population -based cancer registries in the Surveillance , Epidemiology , and End Results ( SEER ) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping ( Inno-LiPA ) , HPV16 viral load , and HPV16 mRNA expression . Trends in HPV prevalence across four calendar periods were estimated by using logistic regression . Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonr and om selection and to calculate incidence trends . Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses . RESULTS HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay ( P trend < .05 ) . For example , HPV prevalence by Inno-LiPA  increased from 16.3 % during 1984 to 1989 to 71.7 % during 2000 to 2004 . Median survival was significantly longer for HPV-positive than for HPV-negative patients ( 131 v 20 months ; log-rank P < .001 ; adjusted hazard ratio , 0.31 ; 95 % CI , 0.21 to 0.46 ) . Survival significantly increased across calendar periods for HPV-positive ( P = .003 ) but not for HPV-negative patients ( P = .18 ) . Population -level incidence of HPV-positive oropharyngeal cancers increased by 225 % ( 95 % CI , 208 % to 242 % ) from 1988 to 2004 ( from 0.8 per 100,000 to 2.6 per 100,000 ) , and incidence for HPV-negative cancers declined by 50 % ( 95 % CI , 47 % to 53 % ; from 2.0 per 100,000 to 1.0 per 100,000 ) . If recent incidence trends continue , the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020 . CONCLUSION Increases in the population -level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection BACKGROUND Elective treatment of the neck in oral squamous cell carcinoma has changed over the last 20 years . The main object of this report is to present the results of a multi-institutional prospect i ve study design ed to compare st and ard treatment with modified radical classical neck dissection ( MRND ) to supraomohyoid neck dissection ( SOH ) in the management of the clinical ly negative neck in oral cancer patients . PATIENTS AND METHODS A total of 148 patients were included in the trial . All patients had previously untreated T2 to T4 N0 squamous cell carcinoma of the oral tongue ( 62 cases ) , floor of the mouth ( 49 cases ) , inferior gingiva ( 12 cases ) , or retromolar trigone ( 25 cases ) . Tumor stages were T2 , 91 ; T3 , 27 ; and T4 , 30 . There were no significant imbalances between groups . RESULTS The false-negative rate was 28 % , and most positive nodes were sited at level II and III . Complications were seen in 41 % of MRND patients and in 25 % of SOH patients ( P = 0.043 ) . Median total duration of hospitalization was 9 days in MRND patients and 7 days in the SOH group . To date , 19 and 16 patients presented with local and neck recurrences , respectively . The 60-month actuarial survival rates were 63 % in the MRND group and 67 % in the SOH group ( P = 0.7150 ) . CONCLUSIONS This study demonstrates that the recurrence and survival rates were similar in both groups . SOH neck dissection can be recommended as st and ard elective treatment for patients with T2-T4 oral squamous cell carcinomas Background Oral cancer is a major health problem worldwide . The 5-year survival rate ranges from 30 - 60 % , and has remained unchanged in the past few decades . This is mainly due to late diagnosis and high recurrence of the disease . Of the patients who receive treatment , up to one third suffer from a recurrence or a second primary tumor . It is apparent that one major cause of disease recurrence is clinical ly unrecognized field changes which extend beyond the visible tumor boundary . We have previously developed an approach using fluorescence visualization ( FV ) technology to improve the recognition of the field at risk surrounding a visible oral cancer that needs to be removed and preliminary results have shown a significant reduction in recurrence rates . Method / Design This paper describes the study design of a r and omized , multi-centre , double blind , controlled surgical trial , the COOLS trial . Nine institutions across Canada will recruit a total of 400 patients with oral severe dysplasia or carcinoma insitu ( N = 160 ) and invasive squamous cell carcinoma ( N = 240 ) . Patients will be stratified by participating institution and histology grade and r and omized equally into FV-guided surgery ( experimental arm ) or white light-guided surgery ( control arm ) . The primary endpoint is a composite of recurrence at or 1 cm within the previous surgery site with 1 ) the same or higher grade histology compared to the initial diagnosis ( i.e. , the diagnosis used for r and omization ) ; or 2 ) further treatment due to the presence of severe dysplasia or higher degree of change at follow-up . This is the first r and omized , multi-centre trial to vali date the effectiveness of the FV-guided surgery . Discussion In this paper we described the strategies , novelty , and challenges of this unique trial involving a surgical approach guided by the FV technology . The success of the trial requires training , coordination , and quality assurance across multiple sites within Canada . The COOLS trial , an example of translational research , may result in reduced recurrence rates following surgical treatment of early-stage oral cancer with significant impacts on survival , morbidity , patients ' quality of life and the cost to the health care system . Trial Registration Clinical trials.gov PURPOSE The purpose of simultaneous chemoradiotherapy is to increase local tumor control and to decrease the incidence of distant metastases .  Platinum-based chemotherapy regimens are widely accepted as st and ard treatment in advanced head and neck cancer . Due to their remarkable activity as well as radiosensitizing effects , taxanes play in increasing role in multimodality treatment concepts of solid tumors . MATERIAL AND METHODS Since 1989 a total of 85 patients with advanced squamous cell carcinoma of the oral cavity and oropharynx were recruited to participate in two different prospect i ve clinical trials of preoperative chemoradiation . Both treatment concepts ( study A : cisplatin 12.5 mg/m(2 ) plus radiation 36 Gy vs study B : Taxol 40 mg/m(2)/carboplatin AUC 1.5 plus radiation 40 Gy ) were compared and further statistical analysis including descriptive analysis as well as univariate and multivariate analysis was performed . RESULTS At the time of the analysis a total of 47 patients ( 55.3 % ) were alive , 38 patients ( 44.7 % ) died from tumor-related causes . The overall survival for both patient groups at 5 years was 45.1 % ( study A ) and 84.9 % ( study B ) and after 10 years 32.4 % for study group A. A comparative analysis of both groups revealed a highly significant survival benefit at 4 years for study B ( p=0.0015 ) . In various calculation models of the multivariate analysis the regimen containing Taxol/carboplatin ( study B ) was superior to the cisplatin regimen ( study A ) . CONCLUSION Based on a retrospective analysis of two different concepts of preoperative chemoradiation and supported by recent data from the literature it is justified to conclude that taxane-based combination regimens are more effective compared to cisplatin-based regimens PURPOSE To determine whether , in the postoperative setting , accelerated fractionation ( AF ) radiotherapy ( RT ) yields a superior locoregional control rate compared with conventional fractionation ( CF ) RT in locally advanced squamous cell carcinomas of the oral cavity , oropharynx , larynx , or hypopharynx . METHODS AND MATERIAL S Patients from four institutions with one or more high-risk features ( pT4 , positive resection margins , pN > 1 , perineural/lymphovascular invasion , extracapsular extension , subglottic extension ) after surgery were r and omly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF . Accelerated fractionation consisted of a " biphasic concomitant boost " schedule , with the boost delivered during the first and last weeks of treatment , to deliver 64 Gy in 5 weeks . Informed consent was obtained . The primary endpoint of the study was locoregional control . Analysis was on an intention-to-treat basis . RESULTS From March 1994 to August 2000 , 226 patients were r and omized . At a median follow-up of 30.6 months ( range , 0 - 110 months ) , 2-year locoregional control estimates were 80 % + /- 4 % for CF and 78 % + /- 5 % for AF ( p = 0.52 ) , and 2-year overall survival estimates were 67 % + /- 5 % for CF and 64 % + /- 5 % for AF ( p = 0.84 ) . The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis . However , interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF ( hazard ratio = 0.5 , 95 % confidence interval 0.2 - 1.1 ) . Fifty percent of patients treated with AF developed confluent mucositis , compared with only 27 % of those treated with CF ( p = 0.006 ) . However , mucositis duration was not different between arms . Although preliminary , actuarial Grade 3 + late toxicity estimates at 2 years were 18 % + /- 4 % and 27 % + /- 6 % for CF and AF , respectively ( p = 0.10 ) . CONCLUSION Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection ; however , AF might be an option for patients who delay starting RT One hundred patients with stage II and stage III cancer of the oropharynx and hypopharynx were treated under a protocol in which they were r and omly selected for treatment by surgery alone or by combined preoperative radiotherapy and surgery . The schedule of preoperative radiation therapy chosen was 2,000 rads from a cobalt 60 machine delivered in five days . Eighty-six of the patients were evaluable at three years ; there was no difference in the outcome of the treatment of the two groups . A similar study is urgently needed to determine the value of postoperative radiotherapy in the management of similar cancers From 1971 to 1975 , 100 patients with glottic , supraglottic , and oral cavity lesions were prospect ively r and omized between primary radiation treatment  and primary surgery .  Local control and survival were similar with either treatment for lesions of the oral cavity or supraglottic larynx . Comparison between radiation alone and surgery alone for T1 and T2 glottic laryngeal lesions showed local control rates of 76 % and 100 % ( P=0.32 ) ; after secondary salvage attempts , local control rates were 82 % and 100 % , respectively ( P= 0.52 ) . Neither result approached statistical significance . Successful radiation for early glottic larynx lesions result ed in superior deglutition and equivalent voice function compared to successful primary treatment with conservation laryngectomy . For oral cavity lesions , swallowing was impaired in the same percentage of radiated and operated patients , but fewer primary radiation patients had articulation difficulties . Among the patients with supraglottic larynx lesions , aspiration was not a problem with either radiation or surgery , but successful radiation perhaps maintained a slightly better voice quality A prospect i ve , r and omized trial was carried out to assess the value of elective versus therapeutic neck dissection in early squamous cell carcinoma of the oral tongue .  Disease-free survival ( median follow-up 20 months ) was 52 percent versus 63 percent in patients who underwent hemiglossectomy alone  and those who underwent hemiglossectomy and radical neck dissection  , respectively ( difference not statistically significant ) . Patients with a tumor depth of less than 4 mm did significantly better than those with a tumor depth of greater than 4 mm ; they were also more likely to have uninvolved nodes at elective radical neck dissection compared with those with a tumor depth of greater than 4 mm . However , when the survival rates of patients in the two treatment groups were compared with respect to a tumor depth of 4 mm , there was no significant difference between the hemiglossectomy and the hemig 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: PURPOSE Recent increases in incidence and survival of oropharyngeal cancers in the United States have been attributed to human papillomavirus ( HPV ) infection , but empirical evidence is lacking . PATIENTS AND METHODS HPV status was determined for all 271 oropharyngeal cancers ( 1984 - 2004 ) collected by the three population -based cancer registries in the Surveillance , Epidemiology , and End Results ( SEER ) Residual Tissue Repositories Program by using polymerase chain reaction and genotyping ( Inno-LiPA ) , HPV16 viral load , and HPV16 mRNA expression . Trends in HPV prevalence across four calendar periods were estimated by using logistic regression . Observed HPV prevalence was reweighted to all oropharyngeal cancers within the cancer registries to account for nonr and om selection and to calculate incidence trends . Survival of HPV-positive and HPV-negative patients was compared by using Kaplan-Meier and multivariable Cox regression analyses . RESULTS HPV prevalence in oropharyngeal cancers significantly increased over calendar time regardless of HPV detection assay ( P trend < .05 ) . For example , HPV prevalence by Inno-LiPA  increased from 16.3 % during 1984 to 1989 to 71.7 % during 2000 to 2004 . Median survival was significantly longer for HPV-positive than for HPV-negative patients ( 131 v 20 months ; log-rank P < .001 ; adjusted hazard ratio , 0.31 ; 95 % CI , 0.21 to 0.46 ) . Survival significantly increased across calendar periods for HPV-positive ( P = .003 ) but not for HPV-negative patients ( P = .18 ) . Population -level incidence of HPV-positive oropharyngeal cancers increased by 225 % ( 95 % CI , 208 % to 242 % ) from 1988 to 2004 ( from 0.8 per 100,000 to 2.6 per 100,000 ) , and incidence for HPV-negative cancers declined by 50 % ( 95 % CI , 47 % to 53 % ; from 2.0 per 100,000 to 1.0 per 100,000 ) . If recent incidence trends continue , the annual number of HPV-positive oropharyngeal cancers is expected to surpass the annual number of cervical cancers by the year 2020 . CONCLUSION Increases in the population -level incidence and survival of oropharyngeal cancers in the United States since 1984 are caused by HPV infection BACKGROUND Elective treatment of the neck in oral squamous cell carcinoma has changed over the last 20 years . The main object of this report is to present the results of a multi-institutional prospect i ve study design ed to compare st and ard treatment with modified radical classical neck dissection ( MRND ) to supraomohyoid neck dissection ( SOH ) in the management of the clinical ly negative neck in oral cancer patients . PATIENTS AND METHODS A total of 148 patients were included in the trial . All patients had previously untreated T2 to T4 N0 squamous cell carcinoma of the oral tongue ( 62 cases ) , floor of the mouth ( 49 cases ) , inferior gingiva ( 12 cases ) , or retromolar trigone ( 25 cases ) . Tumor stages were T2 , 91 ; T3 , 27 ; and T4 , 30 . There were no significant imbalances between groups . RESULTS The false-negative rate was 28 % , and most positive nodes were sited at level II and III . Complications were seen in 41 % of MRND patients and in 25 % of SOH patients ( P = 0.043 ) . Median total duration of hospitalization was 9 days in MRND patients and 7 days in the SOH group . To date , 19 and 16 patients presented with local and neck recurrences , respectively . The 60-month actuarial survival rates were 63 % in the MRND group and 67 % in the SOH group ( P = 0.7150 ) . CONCLUSIONS This study demonstrates that the recurrence and survival rates were similar in both groups . SOH neck dissection can be recommended as st and ard elective treatment for patients with T2-T4 oral squamous cell carcinomas Background Oral cancer is a major health problem worldwide . The 5-year survival rate ranges from 30 - 60 % , and has remained unchanged in the past few decades . This is mainly due to late diagnosis and high recurrence of the disease . Of the patients who receive treatment , up to one third suffer from a recurrence or a second primary tumor . It is apparent that one major cause of disease recurrence is clinical ly unrecognized field changes which extend beyond the visible tumor boundary . We have previously developed an approach using fluorescence visualization ( FV ) technology to improve the recognition of the field at risk surrounding a visible oral cancer that needs to be removed and preliminary results have shown a significant reduction in recurrence rates . Method / Design This paper describes the study design of a r and omized , multi-centre , double blind , controlled surgical trial , the COOLS trial . Nine institutions across Canada will recruit a total of 400 patients with oral severe dysplasia or carcinoma insitu ( N = 160 ) and invasive squamous cell carcinoma ( N = 240 ) . Patients will be stratified by participating institution and histology grade and r and omized equally into FV-guided surgery ( experimental arm ) or white light-guided surgery ( control arm ) . The primary endpoint is a composite of recurrence at or 1 cm within the previous surgery site with 1 ) the same or higher grade histology compared to the initial diagnosis ( i.e. , the diagnosis used for r and omization ) ; or 2 ) further treatment due to the presence of severe dysplasia or higher degree of change at follow-up . This is the first r and omized , multi-centre trial to vali date the effectiveness of the FV-guided surgery . Discussion In this paper we described the strategies , novelty , and challenges of this unique trial involving a surgical approach guided by the FV technology . The success of the trial requires training , coordination , and quality assurance across multiple sites within Canada . The COOLS trial , an example of translational research , may result in reduced recurrence rates following surgical treatment of early-stage oral cancer with significant impacts on survival , morbidity , patients ' quality of life and the cost to the health care system . Trial Registration Clinical trials.gov PURPOSE The purpose of simultaneous chemoradiotherapy is to increase local tumor control and to decrease the incidence of distant metastases .  Platinum-based chemotherapy regimens are widely accepted as st and ard treatment in advanced head and neck cancer . Due to their remarkable activity as well as radiosensitizing effects , taxanes play in increasing role in multimodality treatment concepts of solid tumors . MATERIAL AND METHODS Since 1989 a total of 85 patients with advanced squamous cell carcinoma of the oral cavity and oropharynx were recruited to participate in two different prospect i ve clinical trials of preoperative chemoradiation . Both treatment concepts ( study A : cisplatin 12.5 mg/m(2 ) plus radiation 36 Gy vs study B : Taxol 40 mg/m(2)/carboplatin AUC 1.5 plus radiation 40 Gy ) were compared and further statistical analysis including descriptive analysis as well as univariate and multivariate analysis was performed . RESULTS At the time of the analysis a total of 47 patients ( 55.3 % ) were alive , 38 patients ( 44.7 % ) died from tumor-related causes . The overall survival for both patient groups at 5 years was 45.1 % ( study A ) and 84.9 % ( study B ) and after 10 years 32.4 % for study group A. A comparative analysis of both groups revealed a highly significant survival benefit at 4 years for study B ( p=0.0015 ) . In various calculation models of the multivariate analysis the regimen containing Taxol/carboplatin ( study B ) was superior to the cisplatin regimen ( study A ) . CONCLUSION Based on a retrospective analysis of two different concepts of preoperative chemoradiation and supported by recent data from the literature it is justified to conclude that taxane-based combination regimens are more effective compared to cisplatin-based regimens PURPOSE To determine whether , in the postoperative setting , accelerated fractionation ( AF ) radiotherapy ( RT ) yields a superior locoregional control rate compared with conventional fractionation ( CF ) RT in locally advanced squamous cell carcinomas of the oral cavity , oropharynx , larynx , or hypopharynx . METHODS AND MATERIAL S Patients from four institutions with one or more high-risk features ( pT4 , positive resection margins , pN > 1 , perineural/lymphovascular invasion , extracapsular extension , subglottic extension ) after surgery were r and omly assigned to either RT with one daily session of 2 Gy up to 60 Gy in 6 weeks or AF . Accelerated fractionation consisted of a " biphasic concomitant boost " schedule , with the boost delivered during the first and last weeks of treatment , to deliver 64 Gy in 5 weeks . Informed consent was obtained . The primary endpoint of the study was locoregional control . Analysis was on an intention-to-treat basis . RESULTS From March 1994 to August 2000 , 226 patients were r and omized . At a median follow-up of 30.6 months ( range , 0 - 110 months ) , 2-year locoregional control estimates were 80 % + /- 4 % for CF and 78 % + /- 5 % for AF ( p = 0.52 ) , and 2-year overall survival estimates were 67 % + /- 5 % for CF and 64 % + /- 5 % for AF ( p = 0.84 ) . The lack of difference in outcome between the two treatment arms was confirmed by multivariate analysis . However , interaction analysis with median values as cut-offs showed a trend for improved locoregional control for those patients who had a delay in starting RT and who were treated with AF compared with those with a similar delay but who were treated with CF ( hazard ratio = 0.5 , 95 % confidence interval 0.2 - 1.1 ) . Fifty percent of patients treated with AF developed confluent mucositis , compared with only 27 % of those treated with CF ( p = 0.006 ) . However , mucositis duration was not different between arms . Although preliminary , actuarial Grade 3 + late toxicity estimates at 2 years were 18 % + /- 4 % and 27 % + /- 6 % for CF and AF , respectively ( p = 0.10 ) . CONCLUSION Accelerated fractionation does not seem to be worthwhile for squamous cell carcinoma of the head and neck after resection ; however , AF might be an option for patients who delay starting RT One hundred patients with stage II and stage III cancer of the oropharynx and hypopharynx were treated under a protocol in which they were r and omly selected for treatment by surgery alone or by combined preoperative radiotherapy and surgery . The schedule of preoperative radiation therapy chosen was 2,000 rads from a cobalt 60 machine delivered in five days . Eighty-six of the patients were evaluable at three years ; there was no difference in the outcome of the treatment of the two groups . A similar study is urgently needed to determine the value of postoperative radiotherapy in the management of similar cancers From 1971 to 1975 , 100 patients with glottic , supraglottic , and oral cavity lesions were prospect ively r and omized between primary radiation treatment  and primary surgery .  Local control and survival were similar with either treatment for lesions of the oral cavity or supraglottic larynx . Comparison between radiation alone and surgery alone for T1 and T2 glottic laryngeal lesions showed local control rates of 76 % and 100 % ( P=0.32 ) ; after secondary salvage attempts , local control rates were 82 % and 100 % , respectively ( P= 0.52 ) . Neither result approached statistical significance . Successful radiation for early glottic larynx lesions result ed in superior deglutition and equivalent voice function compared to successful primary treatment with conservation laryngectomy . For oral cavity lesions , swallowing was impaired in the same percentage of radiated and operated patients , but fewer primary radiation patients had articulation difficulties . Among the patients with supraglottic larynx lesions , aspiration was not a problem with either radiation or surgery , but successful radiation perhaps maintained a slightly better voice quality A prospect i ve , r and omized trial was carried out to assess the value of elective versus therapeutic neck dissection in early squamous cell carcinoma of the oral tongue .  Disease-free survival ( median follow-up 20 months ) was 52 percent versus 63 percent in patients who underwent hemiglossectomy alone  and those who underwent hemiglossectomy and radical neck dissection  , respectively ( difference not statistically significant ) . Patients with a tumor depth of less than 4 mm did significantly better than those with a tumor depth of greater than 4 mm ; they were also more likely to have uninvolved nodes at elective radical neck dissection compared with those with a tumor depth of greater than 4 mm . However , when the survival rates of patients in the two treatment groups were compared with respect to a tumor depth of 4 mm , there was no significant difference between the hemiglossectomy and the hemig 
    Output:
    