Absent/weak CD44 intensity and positive human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma indicates a very high survival

Patients with human papillomavirus DNA positive (HPV(DNA)+) oropharyngeal squamous cell carcinoma (OSCC) have better clinical outcome than those with HPV DNA negative (HPV(DNA)−) OSCC upon intensive oncological treatment. All HPV(DNA)+ OSCC patients may not require intensive treatment, however, but before potentially deintensifying treatment, additional predictive markers are needed. Here, we examined HPV, p16(INK4a), and CD44 in OSCC in correlation to clinical outcome. Pretreatment tumors from 290 OSCC patients, the majority not receiving chemotherapy, were analyzed for HPV DNA by Luminex and for p16(INK4a) and CD44 by immunohistochemistry. 225/290 (78%) tumors were HPV(DNA)+ and 211/290 (73%) overexpressed p16(INK4a), which correlated to presence of HPV (P < 0.0001). Presence of HPV DNA, absent/weak CD44 intensity staining correlated to favorable 3-year disease-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis, and likewise for p16(INK4a) by univariate analysis. Upon stratification for HPV, HPV(DNA)+ OSCC with absent/weak CD44 intensity presented the significantly best 3-year DFS and OS, with >95% 3-year DFS and OS. Furthermore, in HPV(DNA)+ OSCC, p16(INK4a)+ overexpression correlated to a favorable 3-year OS. In conclusion, patients with HPV(DNA)+ and absent/weak CD44 intensity OSCC presented the best survival and this marker combination could possibly be used for selecting patients for tailored deintensified treatment in prospective clinical trials. Absence of/weak CD44 or presence of human papillomavirus (HPV) DNA was shown as a favorable prognostic factors in tonsillar and tongue base cancer. Moreover, patients with the combination of absence of/weak CD44 and presence of HPV DNA presented a very favorable outcome. Therefore, we suggest that this marker combination could potentially be used to single out patients with a high survival that could benefit from a de-escalated oncological treatment.