***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: BACKGROUND Oropharyngeal squamous-cell carcinomas caused by human papillomavirus ( HPV ) are associated with favorable survival , but the independent prognostic significance of tumor HPV status remains unknown . METHODS We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a r and omized trial comparing accelerated-fractionation radiotherapy ( with acceleration by means of concomitant boost radiotherapy ) with st and ard-fractionation radiotherapy , each combined with cisplatin therapy  , in patients with squamous-cell carcinoma of the head and neck . Proportional-hazards models were used to compare the risk of death among patients with HPV-positive cancer and those with HPV-negative cancer . RESULTS The median follow-up period was 4.8 years . The 3-year rate of overall survival was similar in the group receiving accelerated-fractionation radiotherapy and the group receiving st and ard-fractionation radiotherapy ( 70.3 % vs. 64.3 % ; P=0.18 ; hazard ratio for death with accelerated-fractionation radiotherapy , 0.90 ; 95 % confidence interval [ CI ] , 0.72 to 1.13 ) , as were the rates of high- grade acute and late toxic events . A total of 63.8 % of patients with oropharyngeal cancer ( 206 of 323 ) had HPV-positive tumors ; these patients had better 3-year rates of overall survival ( 82.4 % , vs. 57.1 % among patients with HPV-negative tumors ; P<0.001 by the log-rank test ) and , after adjustment for age , race , tumor and nodal stage , tobacco exposure , and treatment assignment , had a 58 % reduction in the risk of death ( hazard ratio , 0.42 ; 95 % CI , 0.27 to 0.66 ) . The risk of death significantly increased with each additional pack-year of tobacco smoking . Using recursive-partitioning analysis , we classified our patients as having a low , intermediate , or high risk of death on the basis of four factors : HPV status , pack-years of tobacco smoking , tumor stage , and nodal stage . CONCLUSIONS Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer . ( Clinical Trials.gov number , NCT00047008 . Purpose Treatment of oropharyngeal squamous cell carcinoma ( OPSCC ) is evolving toward risk-based modification of therapeutic intensity , which requires patient-specific estimates of overall survival ( OS ) and progression-free survival ( PFS ) . Methods To develop and vali date nomograms for OS and PFS , we used a derivation cohort of 493 patients with OPSCC with known p16 tumor status ( surrogate of human papillomavirus ) and cigarette smoking history ( pack-years ) r and omly assigned to clinical trials using platinum-based chemoradiotherapy ( NRG Oncology Radiation Therapy Oncology Group [ RTOG ] 0129 and 0522 ) . Nomograms were created from Cox models and internally vali date d by use of bootstrap and cross-validation . Model discrimination was measured by calibration plots and the concordance index . Nomograms were externally vali date d in a cohort of 153 patients with OPSCC r and omly assigned to a third trial , NRG Oncology RTOG 9003 . Results Both models included age , Zubrod performance status , pack-years , education , p16 status , and T and N stage ; the OS model also included anemia and age × pack-years interaction ; and the PFS model also included marital status , weight loss , and p16 × Zubrod interaction . Predictions correlated well with observed 2-year and 5-year outcomes . The uncorrected concordance index was 0.76 ( 95 % CI , 0.72 to 0.80 ) for OS and 0.70 ( 95 % CI , 0.66 to 0.74 ) for PFS , and bias-corrected indices were similar . In the validation set , OS and PFS models were well calibrated , and OS and PFS were significantly different across tertiles of nomogram scores ( log-rank P = .003 ; < .001 ) . Conclusion The vali date d nomograms provided useful prediction of OS and PFS for patients with OPSCC treated with primary radiation-based therapy Purpose The aim of this prospect i ve case series study was to determine the prevalence of HPV-DNA , analyze the E6 mRNA expression , identify intra-type variation in the E6 oncogene in upper aerodigestive tract ( UADT ) squamous cell carcinoma ( SCC ) , and correlate the presence of HPV-DNA with several clinical parameters and outcome . Methods Frozen sample s of UADT-SCC were analyzed for the presence and characterization of HPV-DNA and RNA sequences by means of polymerase chain reaction ( PCR ) , reverse transcriptase-PCR , and direct sequencing of amplified products . Results HPV-DNA sequences were detected in 10 % of the tumors , all of which were typed as HPV-16 . Positivity for HPV-16 E6/E7 mRNA was observed in five of the eight HPV-positive tumors ( 62.5 % ) . The HPV-16 E6 L83V variant was present in five cases . Multivariate analysis identified a history of absence of smoking ( P = 0.009 ) as a predictor of HPV-positive tumor . No significant differences in overall and disease free survival curves were observed between patients with HPV-positive tumors and patients with tumors without detectable HPV-DNA . Conclusion Our findings support the etiological participation of HPV-16 in a subset of UADT-SCCs from patients lacking traditional risk factors . The potential prognostic significance of HPV-16 E6 L83V variant in HPV-16 positive UADT-SCCs should be more extensively investigated PURPOSE Although p16 protein expression , a surrogate marker of oncogenic human papillomavirus ( HPV ) infection , is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma ( OPSCC ) , its prevalence and significance have not been well established in cancer of the oral cavity , hypopharynx , or larynx , collectively referred as non-OPSCC , where HPV infection is less common than in the oropharynx . PATIENTS AND METHODS p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies were determined by immunohistochemistry ( IHC ) and in situ hybridization ( ISH ) . Hazard ratios from Cox models were expressed as positive or negative , stratified by trial , and adjusted for clinical characteristics . RESULTS p16 expression was positive in 14.1 % ( 12 of 85 ) , 24.2 % ( 23 of 95 ) , and 19.0 % ( 27 of 142 ) and HPV ISH was positive in 6.5 % ( six of 93 ) , 14.6 % ( 15 of 103 ) , and 6.9 % ( seven of 101 ) of non-OPSCCs from RTOG 0129 , 0234 , and 0522 studies , respectively . Hazard ratios for p16 expression were 0.63 ( 95 % CI , 0.42 to 0.95 ; P = .03 ) and 0.56 ( 95 % CI , 0.35 to 0.89 ; P = .01 ) for progression-free ( PFS ) and overall survival ( OS ) , respectively . Comparing OPSCC and non-OPSCC , patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC , but patients with p16-negative OPSCC and non-OPSCC have similar outcomes . CONCLUSION Similar to results in patients with OPSCC , patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC , and HPV may also have a role in outcome in a subset of non-OPSCC . However , further development of a  p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting PURPOSE To determine the prognostic importance of p16 and human papillomavirus ( HPV ) in patients with oropharyngeal cancer treated on a phase III concurrent chemoradiotherapy trial . PATIENTS AND METHODS Patients with stage III or IV head and neck squamous cell cancer were r and omly assigned to concurrent radiotherapy and cisplatin with or without tirapazamine . In this sub study , analyses were restricted to patients with oropharyngeal cancer . p16 was detected by immunohistochemistry , and HPV was detected by in situ hybridization and polymerase chain reaction . RESULTS Slides were available for p16 assay in 206 of 465 patients , of which 185 were eligible , and p16 and HPV were evaluable in 172 patients . One hundred six ( 57 % ) of 185 were p16-positive , and in patients evaluable for both p16 and HPV , 88 ( 86 % ) of 102 p16-positive patients were also HPV-positive . Patients who were p16-positive had lower T and higher N categories and better Eastern Cooperative Oncology Group ( ECOG ) performance status . p16-positive tumors compared with p16-negative tumors were associated with better 2-year overall survival ( 91 % v 74 % ; hazard ratio [ HR ] , 0.36 ; 95 % CI , 0.17 to 0.74 ; P = .004 ) and failure-free survival ( 87 % v 72 % ; HR , 0.39 ; 95 % CI , 0.20 to 0.74 ; P = .003 ) . p16 was a significant prognostic factor on multivariable analysis ( HR , 0.45 ; 95 % CI , 0.21 to 0.96 ; P = .04 ) . p16-positive patients had lower rates of locoregional failure and deaths due to other causes . There was a trend favoring the tirapazamine arm for improved locoregional control in p16-negative patients ( HR , 0.33 ; 95 % CI , 0.09 to 1.24 ; P = .13 ) . CONCLUSION HPV-associated oropharyngeal cancer is a distinct entity with a favorable prognosis compared with HPV-negative oropharyngeal cancer when treated with cisplatin-based chemoradiotherapy Background : Following chemo-radiotherapy ( CCRT ) for human papilloma virus positive ( HPV+ ) locally advanced head and neck cancer , patients frequently undergo unnecessary neck dissection ( ND ) and /or repeated biopsies for abnormal PET-CT , which causes significant morbidity . We assessed the role of circulating HPV DNA in identifying ‘ true ’ residual disease . Methods : We prospect ively recruited test ( n=55 ) and validation ( n=33 ) cohorts . HPV status was confirmed by E7 RT-PCR . We developed a novel amplicon-based next generation sequencing assay ( HPV16-detect ) to detect circulating HPV DNA . Circulating HPV DNA levels post-CCRT were correlated to disease response ( PET-CT ) . Results : In pre-CCRT plasma , HPV-detect demonstrated 100 % sensitivity and 93 % specificity , and 90 % sensitivity and 100 % specificity for the test ( 27 HPV+ ) and validation ( 20 HPV+ ) cohorts , respectively . Thirty-six out of 37 patients ( test and validation cohort ) with complete sample s-set had negative HPV-detect at end of treatment . Six patients underwent ND ( 3 ) and repeat primary site biopsies ( 3 ) for positive PET-CT but had no viable tumour . One patient had positive HPV-detect and positive PET-CT and liver biopsy , indicating 100 % agreement for HPV-detect and residual cancer . Conclusions : We demonstrate that HPV16-detect is a highly sensitive and specific test for identification of HPV DNA in plasma at diagnosis . HPV DNA post-treatment correlates with clinical response 
    Output:
    
Conclusion This study evaluated the survival impact of HPV infection in LSCC patients .
The OS of the HPV‐positive group was better than that of the HPV‐negative group in terms of short‐term survival .