25267748
OBJECTIVE	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 .
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 ) .
METHODS	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 .
RESULTS	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 .
RESULTS	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 .
CONCLUSIONS	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 .
CONCLUSIONS	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 .

