***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 The improved prognosis for patients with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma ( HNSCC ) relative to HPV-negative HNSCC observed in retrospective analyses remains to be confirmed in a prospect i ve clinical trial . METHODS We prospect ively evaluated the association of tumor HPV status with therapeutic response and survival among 96 patients with stage III or IV HNSCC of the oropharynx or larynx who participated in an Eastern Cooperative Oncology Group ( ECOG ) phase II trial and who received two cycles of induction chemotherapy with intravenous paclitaxel and carboplatin followed by concomitant weekly intravenous paclitaxel and st and ard fractionation radiation therapy .  The presence or absence of HPV oncogenic types in tumors was determined by multiplex polymerase chain reaction ( PCR ) and in situ hybridization . Two-year overall and progression-free survival for HPV-positive and HPV-negative patients were estimated by Kaplan-Meier analysis . The relative hazard of mortality and progression for HPV-positive vs HPV-negative patients after adjustment for age , ECOG performance status , stage , and other covariables was estimated by use of a multivariable Cox proportional hazards model . All statistical tests were two-sided . RESULTS Genomic DNA of oncogenic HPV types 16 , 33 , or 35 was located within tumor cell nuclei of 40 % ( 95 % confidence interval [ CI ] = 30 % to 50 % ) of patients with HNSCC of the oropharynx or larynx by in situ hybridization and PCR . Compared with patients with HPV-negative tumors , patients with HPV-positive tumors had higher response rates after induction chemotherapy ( 82 % vs 55 % , difference = 27 % , 95 % CI = 9.3 % to 44.7 % , P = .01 ) and after chemoradiation treatment ( 84 % vs 57 % , difference = 27 % , 95 % CI = 9.7 % to 44.3 % , P = .007 ) . After a median follow-up of 39.1 months , patients with HPV-positive tumors had improved overall survival ( 2-year overall survival = 95 % [ 95 % CI = 87 % to 100 % ] vs 62 % [ 95 % CI = 49 % to 74 % ] , difference = 33 % , 95 % CI = 18.6 % to 47.4 % , P = .005 , log-rank test ) and , after adjustment for age , tumor stage , and ECOG performance status , lower risks of progression ( hazard ratio [ HR ] = 0.27 , 95 % CI = 0.10 to 0.75 ) , and death from any cause ( HR = 0.36 , 95 % CI = 0.15 to 0.85 ) than those with HPV-negative tumors . CONCLUSION For patients with HNSCC of the oropharynx , tumor HPV status is strongly associated with therapeutic response and survival 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 IMPORTANCE Human papillomavirus type 16 ( HPV-16 ) is a major causative factor in oropharyngeal squamous cell carcinoma ( OPSCC ) . The detection of primary OPSCC is often delayed owing to the challenging anatomy of the oropharynx . OBJECTIVE To investigate the feasibility of HPV-16 DNA detection in pretreatment and posttreatment plasma and saliva and its potential role as a marker of prognosis . DESIGN , SETTING , AND PARTICIPANTS This is a retrospective analysis of a prospect ively collected cohort . Among a cohort of patients with oropharyngeal and unknown primary squamous cell carcinoma with known HPV-16 tumor status from the Johns Hopkins Medical Institutions and Greater Baltimore Medical Center ( from 1999 through 2010 ) , 93 patients were identified with a complete set of pretreatment and posttreatment plasma or saliva sample s , of which 81 patients had HPV-16-positive tumors and 12 patients had HPV-16-negative tumors .  Real-time quantitative polymerase chain reaction was used to detect HPV-16 E6 and E7 DNA in saliva and plasma sample s. MAIN OUTCOMES AND MEASURES Main outcomes included sensitivity , specificity , negative predictive value of combined saliva and plasma pretreatment HPV-16 DNA status for detecting tumor HPV-16 status , as well as the association of posttreatment HPV DNA status with clinical outcomes , including recurrence-free survival and overall survival . RESULTS The median follow-up time was 49 months ( range , 0.9 - 181.0 months ) . The sensitivity , specificity , negative predictive value , and positive predictive value of combined saliva and plasma pretreatment HPV-16 DNA status for detecting tumor HPV-16 status were 76 % , 100 % , 42 % , and 100 % , respectively . The sensitivities of pretreatment saliva or plasma alone were 52.8 % and 67.3 % , respectively . In a multivariable analysis , positive posttreatment saliva HPV status was associated with higher risk of recurrence ( hazard ratio [ HR ] , 10.7 ; 95 % CI , 2.36 - 48.50 ) ( P = .002 ) . Overall survival was reduced among those with posttreatment HPV-positive status in saliva ( HR , 25.9 ; 95 % CI , 3.23 - 208.00 ) ( P = .002 ) and those with HPV-positive status in either saliva or plasma but not among patients with HPV-positive status in plasma alone . The combined saliva and plasma posttreatment HPV-16 DNA status was 90.7 % specific and 69.5 % sensitive in predicting recurrence within 3 years . CONCLUSIONS AND RELEVANCE Using a combination of pretreatment plasma and saliva can increase the sensitivity of pretreatment HPV-16 status as a tool for screening patients with HPV-16-positive OPSCC . In addition , analysis of HPV-16 DNA in saliva and plasma after primary treatment may allow for early detection of recurrence in patients with HPV-16-positive OPSCC 
    Output:
    
Plasma HPV-DNA is a promising tool for surveillance in patients with HPV-related HNSCC , that is , OPSCC , and has a high specificity .
By recent technical advances and by increasing follow-up blood sample s , the sensitivity could likely be improved